Beyondspring Inc (BYSI) 2020 Q2 法說會逐字稿

Good morning. And welcome to BeyondSpring's Second Quarter 2020 Financial Results Conference Call. My name is Kevin, and I'll be your operator for today's conversation. Please be advised that this call is being recorded.

At this time, I'd like to turn the call over to Scott Eckstein, Vice President at KCSA Strategic Communications. Scott, please go ahead.

Thank you for joining today's call. I would like to advise listeners that comments made during 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 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, 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?

Yes. Thank you so much, Scott. Good morning, ladies and gentlemen. Thank you for joining today's call. BeyondSpring's mission has been to develop innovative, transformative medicines that improve clinical outcomes in high unmet medical needs for the global market. With our lead asset, first-in-class agent Plinabulin in late-stage development in 2 large oncology market opportunities for chemotherapy-induced neutropenia, or CIN, prevention and non-small cell lung cancer treatment, we believe that we are at a significant inflection point that will potentially result in helping many patients in need and realizing tremendous value for our shareholders. This is the combination of 10 years of hard work at BeyondSpring with our dedicated and experienced team and our partners globally.

In addition, we have a developing clinical and preclinical pipeline with Plinabulin in multiple I/O combo cancer indications, 3 preclinical I/O agents and world-leading targeted protein degradation, TPD, platform to fuel future growth. Dr. Hershko, Nobel Prize winner in the field, is our scientific adviser.

Finally, we have developed global capabilities with strong clinical and regulatory network and developing commercial infrastructure to drive ongoing innovation.

For Plinabulin's first indication, CIN, we expect to file NDA to the USFDA by the end of 2020. We have initiated rolling NDA submission for China NMPA in quarter 1 2020. CIN indication has only 1 drug, G-CSF, approved in the last 30 years. G-CSF class, which has annual revenue of over $9 billion globally and over $7 billion in the U.S. alone. Even with the use of G-CSF, cancer patients undergoing chemo are still experiencing over 80% of Grade 1 neutropenia or very low white blood cells, which will cause severe infection, leading to death and the need to reduce or delay chemo dose or downgrade chemo regime in later cycles, all of this affect chemo's anti-cancer benefit. Therefore, CIN is still a severely unmet medical need.

Since our first IND meeting with the USFDA in September 2016 and the first patient enrolled in the U.S. in April 2017, we have enrolled around 500 patients in the CIN studies to arrive at this significant NDA filing by the end of the year. Along the 4-year journey, Dr. Blayney and Dr. Crawford, U.S. CIN, NCCN Guidelines founding member and former Chairman have been guiding us for the trial design and trial qualities. Plinabulin and G-CSF combination has been shown to be superior in CIN prevention in our clinical studies, which would potentially translate to reduce infection and hospitalization after chemotherapy and enable doctors to provide chemotherapy to their patients without compromise. This means stable doses, sustained cycles and the strongest regime possible, so that patients can stay the course with their treatment for potential survival benefit.

Now let me share with you some detailed clinical and preclinical achievement in the second quarter of 2020. First, the positive top line prespecified interim Phase III data, both from our PROTECTIVE-2 or Study 106, continues to support the superior profile of using Plinabulin in combination with Neulasta versus using Neulasta alone for protection against CIN and demonstrates the potential of the Plinabulin and G-CSF combination to become the first superior therapy and significant enhancement to G-CSF in preventing neutropenia in oral chemo and/or non-myeloid cancer in the last 30 years. I'm also excited to report to you that the enrollment of a total of 221 patients in 106 Phase III study has been completed in July, ahead of schedule, and we expect top line Phase III data will be available in quarter 4 2020.

Second, our DUBLIN-3 trial or 103 study achieved another major milestone, the second interim analysis for non-small cell lung cancer treatment with Plinabulin. As you may recall, DUBLIN-3 is a global Phase III trial for Plinabulin in combination with docetaxel versus docetaxel alone for the treatment of second and third-line EGFR wild-type non-small cell lung cancer and Plinabulin's mechanism-based measurable lung lesion targeted patients. This is a highly unmet medical need indication, as only 4 therapies have been approved, with limited survival benefits and some with debilitating side effects, such as over 40% severe neutropenia. Upon reviewing the efficacy and safety data of more than 500 patients and at around 300 patient death events, the DSMB recommended that the trial continue without any modification based on favorable benefit-risk ratio. We think that the positive trend seen in 2 interim analysis is expected, justified by Plinabulin's I/O mechanism in activating immune defense protein GEF-H1 and positive Phase II subset analysis based on mechanism-targeted patients. We look forward to the final top line data for first half 2021 at 439 death events.

Third, at the AACR meeting in June, we presented data on triple I/O and Plinabulin combo, demonstrating 100% complete response rate in PD-1 nonresponsive tumor models conducted at MD Anderson. We plan to start tripe I/O and the Plinabulin combo study at MD Anderson in second half 2020 with intention to reverse progressive disease of previous PD-1 antibody failed patients. This potential success of the study will showcase Plinabulin's potent activity in antigen-presenting cell or APC induction, serving as a potential cornerstone therapy in cancer treatment. This study would set the stage for Plinabulin as a pipeline in a drug for multiple cancer indications.

Finally, we believe the foundation for an innovative company is patents and talent. For Plinabulin, the composition of matter patent and multiple usage patents are protected till the year 2036 in 36 jurisdictions, including 17 granted patents in the U.S. This gives substantial runway for Plinabulin to realize its commercial potential as a pipeline in a drug.

And for company, we've made some significant additions to our world-class management and our Board of Directors in this quarter. In August, BeyondSpring announced the appointment of Paul Friel to the role of Chief Commercial Officer. Paul has nearly 30 years of experience in the pharmaceutical and biotech industry and successfully launched over 12 drugs. He has held positions as General Manager and President at Takeda Canada and Vice President of Sales for Vyaire. Paul was also instrumental in building TAP Pharmaceuticals and Takeda North America to more than 5,000 employees and $10 billion in sales in less than 10 years during the merger of these companies. We are very excited about this appointment and look forward to Paul's continued contribution in his new role to help our company transform from R&D to R&D and sales.

Also in August, Dr. Ravi Majeti, Co-Founder and former Board member of Forty Seven and Chief of Division of Hematology Stanford University joined our Board of Directors. Dr. Majeti co-founded Forty Seven in 2014 and was a major contributor to the research and technology that led to Forty Seven's $4.9 billion acquisition by Gilead Sciences this past March. With his extensive background and experience, Dr. Majeti can help guide us to translate solid science and clinical data to medicine for patients and well-deserved shareholder value. We look forward to his contributions as an invaluable new member of our Board.

In summary, after 10 years of hard work of researching Plinabulin's unique mechanism and enrolling over 1,000 patients, we have a clearer understanding of Plinabulin's clinical profile and development trajectory. In the next 6 to 18 months, we expect significant clinical and NDA catalysts, which will drive BeyondSpring's transformation into a commercial stage company.

With that, I will now turn the call over to Dr. Ramon Mohanlal, who will discuss our recent clinical developments in more detail. Ramon?

Thank you, Lan. Firstly, I will talk about the CIN program. In the past 5 years, we have brought the CIN program to fruition. And as Lan indicated, we are very proud to announce that even as we speak, we are preparing the CIN NDA. The pivotal trial PROTECTIVE-2, which is now fully enrolled, is nearing its completion. This is a transformational time for us with the company's first NDA filing. We had a number of discussions with the FDA who proactively contributed to our study designs and reviewed all our protocols prior to enrollment. We have had in-depth discussions with the FDA regarding changing the primary endpoint from DSN to the more meaningful end point of grade 4 neutropenia prevention. At the preplanned interim analysis of PROTECTIVE-2, we have met not only the new primary endpoint of grade 4 neutropenia prevention but also met the criteria for the old endpoint of DSN. In anticipation of the final dataset of PROTECTIVE-2, we now have started the preparation of the CIN NDA, which will also include data from PROTECTIVE-1 and other trials with neutropenia data with Plinabulin to include Studies 101, 103 and 105. With a combined dataset, we believe we have the data points needed to satisfy the efficacy and safety requirements as well as other sections as required by the NDA.

The collective dataset provides very strong support for adding Plinabulin to pegfilgrastim. Due to different mechanisms of action, the 2 drugs are complementary to each other, wherein Plinabulin predominantly provides protection in the first week of the cycle and pegfilgrastim predominantly in the second week of the cycle. Combining these 2 agents provide superior CIN protection compared to each of them alone. Together, these 2 agents also come with a more favorable safety profile. Hence, it will make sense that every time an oncologist prescribes pegfilgrastim, or G-CSF, they should consider adding Plinabulin to that.

The indication we are targeting is very broad to include all chemotherapies and all non-myeloid cancers. As mentioned earlier, we believe our collective clinical trial dataset has all the data points required to support the CIN NDA submission, which is planned around December of this year. Combined, we have collected data in more than 1,200 patients, of which more than 700 patients have been dosed with Plinabulin.

Now I will move to the non-small cell lung cancer update. We recently had our DSMB for the second preplanned interim analysis, wherein the DSMB not only reviewed the safety data in an open session but also the efficacy data in a closed session to determine benefit-risk of the Plinabulin-docetaxel combination. Based on their review, the DSMB recommends the trial to continue without modification. We feel that as very positive and are currently moving ahead with completing patient enrollment, which we expect will occur this year.

Just as with all pharmaceutical companies, COVID-19 did impact and continues to impact our time lines. However, we believe the impact will be minimal since we are at the tail end of the trial. The final data analysis will be triggered by reaching the target event number of 439 death cases achieved that we expect in the first half of 2021.

I would like to further remind you of the following. First, Plinabulin's unique anticancer mechanism of release in GEF-H1 has been validated in the Cell Reports paper. Second, in our Phase II study, we showed an OS benefit of 4.6 months, and HR for OS at 0.76 in our target population of having a measurable lung lesion RECIST criteria in the lung. Three, at the first preplanned interim analysis of the Phase III trial 103 in around 150 patients death events, we showed a positive trend of an OS of HR less than 0.75. Four, the target product profile of the Plinabulin-docetaxel combination is to demonstrate superior efficacy, superior safety and superior quality of life over standard of care in second and third line, which is now dominated by docetaxel regimen. With the current standard of care in second and third line, we achieved improved survival; however, at the expense of safety, it is more toxicity and at expensive quality of life. With the Plinabulin-docetaxel combination, not only do we expect superior efficacy over docetaxel alone, but also at reduced toxicity and at improved quality of life. We believe the Plinabulin-docetaxel combination has the potential to become the market leader in second and third line non-small cell lung cancer. As a reminder, approximately 50% of non-small cell lung cancer patients will have to see progression with a checkpoint inhibitor regimen in first line, and this will be a need of a second-line treatment option. The Plinabulin-docetaxel combination will be an ideal treatment option for these patients.

Now I will provide an R&D update. I will start with CIN. The current focus is on nonmyeloid cancers as Plinabulin-pegfilgrastim combination strategy, and we envision that Plinabulin will be added to pegfilgrastim or G-CSF every time these agents will be used. From a medical perspective, we see only upside and no downside, superior CIN protection and without added toxicity and likely with less toxicity. We estimate this combination product will target approximately 75% of the CIN market. There are significant market segments where currently G-CSF is not indicated for use or is listed in the warnings and precaution section of the product label. These segments include hematological malignancies and conditions such as sickle cell disorder. These are market segments that we will now start to address.

Next, I'll move to oncology. Our future direction will focus on triple combination strategies in first line, wherein we will have an agent that can generate immunogens, this could be a chemo or radiotherapy; Plinabulin as a dendritic cell enhancer; and a PD-1/PDL-1 inhibitor. Proof of concept of this triple combination strategy with Plinabulin was presented at the AACR 2020. Currently, preparations are underway to initiate a number of these trials. Regarding our pipeline, we continue to advance our preclinical programs, BPI-002 and BPI-004.

I will now take the opportunity to update you on our medical affairs activities in support of the commercial effort. In response to the COVID-19 pandemic, the National Comprehensive Cancer Network, NCCN, recently updated its guidelines to maximize CIN prevention. This is intended to minimize patients' potential exposure. We recently initiated an expanded access program, EAP, which allows doctors across the U.S. to use Plinabulin for CIN prevention. We are proud to do our part in helping others during the pandemic, and believe that initiating this program will assist patients and health care systems to meet the challenges that have been imposed on them by the current COVID-19 environment.

We have initiated broad outreach and awareness efforts with Plinabulin in CIN. CME programs have been initiated. KOL Advisory Board meetings have commenced. We have initiated discussions with the NCCN. We have increased our presence and sponsoring at influential scientific meetings. We are initiating a number of IIT studies for CIN and cancer indications with the leading cancer centers in the United States.

Publication strategy. Our Plinabulin Phase II CIN data has recently been accepted for publication in a major journal which we view as an important external validation. Additional manuscripts are in preparation, targeted at major journals. We have clinical abstracts accepted at ASCO, ISSCR and ESMO.

In summary, during the second quarter of this year, we continued to advance our CIN and non-small cell lung cancer program. And as discussed, we are now getting ready to bring these programs to fruition with the CIN NDA application this year and the non-small cell lung cancer NDA application next year. In support of our commercial preparation, we have initiated broad net of affairs driven outreach and awareness efforts and have continued advancing our pipeline program.

With that, I'll now turn the call over to Rich who will discuss our commercial and partnership strategy. Rich?

Thanks, Ramon. As we've discussed, our clinical program is robust and continues to generate both strong and compelling data for the potential role that Plinabulin can play in cancer care. I'd like to add my congratulations to our clinical team. We are incredibly excited about the opportunity to improve cancer care for patients. Equally encouraging, our extensive market research has shown oncologists are excited about Plinabulin's potential clinical benefits for their patients. Today, I'll discuss 3 elements that drive our excitement. First, the unmet clinical need; second, the changing market forces in oncology; and third, Plinabulin's commercial strategy for a successful launch. During our discussion, I'll be referencing our ongoing market research that supports our strategy.

First, the unmet need in CIN is significant and recognized. With more than 1.3 million cycles of G-CSF given each year, the CIN market remains an unserved market. CIN is the #1 reason for changes in chemotherapy regimens. These changes take the form of decreased doses, delayed cycles and discontinuation of chemotherapy. Even modest changes in chemotherapy regimens have potentially devastating effects on patient treatment outcomes. In our market research, oncologists were crystal clear as to the importance of preventing CIN. 3/4 of oncologists said it was very to extremely important to prevent CIN. Monotherapy G-CSF are current standard of care, but they are simply not enough to prevent and manage CIN. This is where Plinabulin can become a game-changer.

In our market research, more than 100 practicing oncologists told us the 3 most important characteristics of CIN therapy were: one, keep absolute neutrophil count, or ANC, as high as possible; two, reduce or minimize bone pain; three, improve compliance and persistency with chemotherapy, in other words, avoid the 4 Ds. As you heard earlier, this is the clinical profile of Plinabulin. Oncologists want a therapy that can help them provide more consistent, sustained chemotherapy. Our goal is to provide them with the tools to flip the 4 Ds to the 4 Ss through improved management and control of CIN, a therapy that will help them provide stable doses, sustained cycles, the strongest regimen possible and help them to stay the course.

A vast majority of oncologists, 74%, are enthusiastic about combination therapy approach with Plinabulin. When we ask the same 100 oncologists how likely they are to use Plinabulin in combination with the G-CSF, nearly 2/3 or 64% stated they were highly likely to use the combination therapy. Clearly, oncologists are looking for an improvement in the standard of care.

Our second topic, the changing market forces in oncology. The CIN market is undergoing significant changes, which strongly favor Plinabulin's introduction and long-term prospects. The pandemic is driving a desire for more effective therapies beyond monotherapy G-CSF.

Next, the addressable market expansion. As Ramon mentioned, earlier, we referenced the NCCN guidelines and their update in CIN. The guidelines expanded prophylaxis from high-risk patients, which account for 32% of chemotherapy patients, to both high- and intermediate-risk patients, which now accounts for 69% of all chemotherapy patients. This is an increase in the addressable market of more than 100%.

The next change in oncology is the clinical pathway. Oncology practices use clinical pathways to standardize care while adhering to evidence-based guidelines. Clinical pathways have the potential to improve the effectiveness and efficiency of care. The majority of practices base their clinical pathways on NCCN guidelines.

Next, CIN use concentration. G-CSFs are highly concentrated. 360 oncology accounts represent more than 80% of G-CSF use. This is among the most highly concentrated businesses in oncology.

So how do these factors help us build the Plinabulin strategy? Based on the clinical data we generated, our market research and current oncology market trends, we believe that Plinabulin, a medication that improves therapy by combining with the standard of care, is well positioned to improve patient care and for successful commercialization. A recent ZS study found that 70% of companies, similar to BeyondSpring, those that are oncology focused, launching their first product, are likely to launch on their own in the U.S. This is due to the relative strength that oncology products have on their P&L statements. That is favorable pricing, low cost of goods and focused cost of sales.

We have already initiated our prelaunch activities to prepare us for success in the market. Importantly, this will enable us to optimize shareholder return as we explore partnership opportunities.

So our commercial strategy involves 5 core components. First, we'll be driving awareness over the next 12 months with top payers, key opinion leaders and physicians through educational outreach. Second, as Ramon mentioned, we'll be building the case for guideline adoption. We believe that Plinabulin data, presented earlier by Lan and Ramon, represents a significant advancement in the standard of care in preventing CIN. Based on this, we believe we are well positioned for inclusion in updated NCCN guideline. NCCN submission is being prepared, and we will be ready prior to FDA approval per NCCN submission recommendations.

Third, account and customer outreach. As a combination therapy that builds on the standard of care, Plinabulin is unique in the field. No other product on the market or in development has the potential to make this claim. We want to be sure that customers are aware of our clinical program. To give you a sense of the concentration and magnitude of the opportunity and why we are confident that we can execute this plan, let's look at the value of the top accounts. As noted earlier, 80% of all G-CSF use comes from 360 accounts. This is a highly concentrated opportunity, one that a company like ours can focus on and win. Further, the top 50 accounts represent $1.2 billion of G-CSF use and the top 100 accounts represent $1.8 billion of G-CSF use. Recall that in market research, oncologists had a very favorable response to Plinabulin combined with G-CSF. High users of G-CSF had an even more favorable response to using Plinabulin and were more inclined to use the combination. Since Plinabulin is used in combination with G-CSF, the perfect target list for us is the G-CSF use. Our outreach has already begun.

Fourth, ensuring insurance coverage and access. In our market research, more than 90% of payers told that they plan to include Plinabulin in their formularies per NCCN guidelines due to its ability to improve the standard of care. Payers understand Plinabulin is a unique molecule, one that creates value in combination with G-CSF. And payers indicate that they would treat it as such in contracting and formulary discussions. To ensure appropriate reimbursement, we plan to launch a field reimbursement liaison team from day 1.

Finally, health care practitioners and patient commercial support. Over the next year leading up to and through launch, we will deliver a fully integrated market preparation and launch program to support the successful launch of Plinabulin. Elements include our seasoned commercial launch team and leadership team. We're experienced in building and scaling organizations as well as launching products and leading partnerships. We are prepared for all alternatives. We will execute a well-defined and targeted prelaunch market-shaping program to prepare the market for the launch of Plinabulin. Some of the key elements include large account outreach; NCCN guideline outreach, as mentioned earlier; disease awareness; key opinion leader development; speaker mobilization; physician education, both CME and non-CME; Congress support; medical symposia; publications, as Ramon mentioned; and targeted advisory boards.

Once approved, we'll deliver launch support to drive rapid appropriate uptake of Plinabulin. And this would include 60 to 80 field representatives to drive pull-through and broad oncologist and payer coverage; a field reimbursement team to ensure effective reimbursement, as I mentioned earlier, and that would be from day 1; and patient support services to ensure ease of use, broad access and improved care with patient education and co-pay support programs.

In summary, only Plinabulin has demonstrated the ability to clinically complement the standard of care and improve ANC, reduce grade 4 neutropenia, reduce bone pain and give oncologists the tools they need to enhance treatment outcomes. Plinabulin's clinical performance, along with the evolving medical needs of the oncology community, bode well for the successful launch and long-term commercial success of our drug. In summary, Plinabulin is delivering on the promise of elevating chemotherapy.

With that, I'd like to turn it over to Edward who will provide a financial update. Edward?

Thank you, Rich. I will now briefly discuss our second quarter 2020 financial results. For greater detail related to these 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 second quarter of 2020 were $11 million compared to $5.2 million in the same period last year. The $5.8 million increase was largely attributable to a $4.9 million increase in clinical trial expenses.

SG&A expenses were $2.6 million in the second quarter of 2020 compared to $2.1 million for the same quarter of last year. The $0.5 million increase was mainly due to the increase in costs related to prelaunch preparation of Plinabulin.

Net loss attributable to BeyondSpring in the second quarter of 2020 was $12.8 million compared to $7.4 million for the same period last year.

Our cash and cash equivalents at the end of Q2 was $38.1 million. We are confident that our current cash resources are sufficient to support our clinical trials and NDA submissions in the U.S. for Plinabulin for the CIN indication as well as to advance our immuno-oncology pipeline and protein degradation research platform.

As Lan noted earlier, in June and July, we closed a public offering and a private placement at $13 per share and raised a gross proceed of $33.9 million. These transactions have continued to strengthen our balance sheet and diversified our shareholder base. We intend to use the net proceeds to support the commercialization of Plinabulin, continued clinical and preclinical development and for general corporate purposes.

With that, I'll now turn the call back over to Lan for closing remarks. Lan?

Thanks, Edward. In closing, I would like to thank the patients, our dedicated team, our shareholders and our partners for your strong support in helping us to deliver innovative medicines that can potentially provide superior results than the current standard of care to patients across the world with severely unmet medical needs. This is especially important during the COVID-19 era as our health care system is experiencing unprecedented challenges.

Looking ahead, in the next 6 to 18 months, BeyondSpring will be transforming into a commercial stage company through multiple significant clinical and NDA catalysts. We welcome you to embark on this exciting and meaningful journey with us as we help many patients in need.

Operator, let's open for question and answers. Thank you.

(Operator Instructions) Our first question today is coming from Maury Raycroft from Jefferies.

Congrats on the progress. I guess, first question is just on -- if you could talk more about the NCCN guidelines submission prep for CIN, any thoughts on timing on when you might submit and when the guidelines could get updated? And once updated, I was wondering if you plan on pursuing named patient use in reimbursement.

Yes. Thank you so much, Maury, for this great question. I think I'll let Rich to start and Ramon probably add a few more insights. Rich, please?

Sure. Thanks. Thanks for the question, Maury. So the guidelines are pretty clear, and they're posted on the NCCN website. You can -- it's basically a simple process. It's a 2-page application, so very straightforward. And you can apply up to 6 weeks prior to your approval and the meetings for each advisory committee are scheduled in advance. However, they will, if necessary, as they did with COVID-19, call an emergency meeting and if they deem that the opportunity represents a significant advancement. So for instance, the next meeting is middle of October -- next schedule is in the middle of October. So as Ramon talked about, we've begun our preparation, and we understand the process, and we are fully prepared for the opportunity to get on those guidelines. So with that, I'll turn it over to Ramon, obviously, for any type of named patient program or further commentary on the NCCN guidelines.

Yes. Thanks, Rich. As we speak, we have started discussions with the NCCN leadership. And as Rich pointed out, those are the time lines that we will follow. Thank you.

Got it. And is it possible to potentially get reimbursement for use ahead of an official approval?

That's a really, really good question. So that's a payer question more than an NCCN question, but payers will follow, obviously, the label. They'll look at the label. NCCN, again, on their website, it's very clear that they will actually go outside of label. They'll do what they think is in the best interest of the patient. And then the payers have told us, and we've done extensive research with payers, we've talked to more than 40 regional and national payers, and they told us that NCCN is the thing that will drive their policy and their priorities for what they will reimburse. So they'll look at the label first and then they'll look at NCCN. And cancer obviously is one of those areas where they're really interested in making sure they're not seen as blocking therapy. They want to be sure that they are seen as very patient-friendly, especially if something is devastating as cancer. So it's obviously a very sensitive situation with cancer side. We can't really address each payer or the payer space in total prior to approval. So that's just a difficult question. I think that's a payer-by-payer question. And we really haven't addressed that at this point in time.

Got it. Okay. And then for non-small cell lung cancer, can you provide more granularity into how much the time line shifts are related to COVID versus that event rate or other contributing variables?

Yes. So probably I can start, and then Ramon can add additional insight. So yes, actually, COVID-19 does impact the time line because everybody gets affected. But I think it is minimal since we are doing global enrollment. And also just for China, I think after March, everything seemed back to normal, not like in the U.S. So it's not really much impacted. As you see from Ramon's presentation, the 439 patient death event, which is the full event, is going to be expected for first half of next year. And then we are closing almost at the end of the finishing of the enrollment, the full enrollment this year.

Got it. Okay. And then last question is just if you can talk more about the CIN label expectations. I guess, have you had any discussions with FDA to see if they'll accept use of Plinabulin in combination with all other G-CSFs broadly? And do you see any potential boundaries for what Plinabulin can be combined with?

Yes. So probably I can start, and then Ramon can add additional insights. So for the label discussion, of course, this has to wait until the pre-NDA meeting, which we are planning in the coming months. And from where we are seeing from the Plinabulin profile and also what's the missing link for the G-CSF, would you project a broad label for Plinabulin and G-CSF combination in all myeloid cancers and with all chemo and also can be combined with the G-CSF class. The reason being that no matter what chemo, what cancer it is and CIN is a bone marrow problem, right? So -- and from all the literature, if you look at it, even with the use of G-CSFs, no matter what cancer, what chemo, they always have ANC model between day 6 and day 8 because it takes 8 days to mature neutrophil and G-CSF is still on day 2. So all of the new neutrophils coming out, mature ones, is after day 8 or day 9, right? And Plinabulin's mechanism is protecting the first week, and it has been shown in multiple cancer and multiple chemo. So with that profile, the complementarity of the 2 agents is going to protect the full cycle, no matter what cancer, no matter what chemo it's going to use. And in addition, G-CSF class is all the same, right? And they will approve the biosimilar G-CSF absolutely based on DSN of those -- Neulasta or Neupogen. So we don't see much differences in the G-CSF class versus Neulasta, which is what we are using in the clinical study. So that's a long answer. So I don't know if that answers your question.

Our next question today is coming from Joe Pantginis from H.C. Wainwright.

Thanks for all the color thus far, especially coming up ahead a very nice catalyst for the company. I really have a logistical question that I think is targeted more towards Edward, and that's looking at the burn and potential offsets that we should consider. So obviously, some of these Phase IIIs -- or the Phase IIIs are winding down, so you're going to have a significant drop clinical trial cost there. But then are we anticipating any significant boost in, say, personnel costs? Or how should we view the burn going forward and potential offsets?

Right. Thanks, Joe, for this question. So as you know, we had about $38.1 million at the end of June 30. As we said in the press release, that's sufficient for CIN submission in the U.S., and we currently project the CIN submission by the end of this year. So I think our current cash will last for the next 3 quarters or so. As you will see, the clinical expenses will be largely reduced compared to the previous quarters. As you correctly pointed out, the clinical trials are coming down to an end. However, the commercial cost will start to increase over the next several quarters and as well as head count as we prepare the organization ready for a commercial launch. So I guess we are projecting about a burn of around $15 million every quarter going forward. However, we will need additional cash for the commercialization towards the end of next year in preparation for commercial launches towards the end of next year.

(Operator Instructions) Our next question today is coming from Andy Hsieh from William Blair.

So I have a couple. One is more just kind of housekeeping. Any update on PROTECTIVE-1? I think you -- on the call, you talked extensively about PROTECTIVE-2, and its excellent data from -- looking from a clinical profile -- efficacy clinical profile perspective. So any update on that?

And second, I think it's really interesting that you are allowing expanded access to Plinabulin, just given the fact that it's probably closest thing to real-world experience prior to approval. Maybe some commentary on that motivation behind that and maybe early feedback from participating physicians or institutions?

And maybe kind of a related question for Rich. How do you think about potential revenues from the expanded access program? And I have a follow-up after these.

Yes. Thank you so much, Andy, for the great questions, and thank you for your support all along. If I can just answer, the quick answer for the PROTECTIVE-1 and then Ramon will answer on the EAP, and then Rich will answer for your revenue question. So for the PROTECTIVE-1, this -- our interim analysis for the first 105 patients has completed, I think, last year, right? And we had a press release at end of 2018, showing that we did meet the statistical significance for the primary endpoint showing the DSN noninferiority for Plinabulin versus Neulasta alone. So these things we are going forward with the combination label for G-CSF and Plinabulin. So for the PROTECTIVE-1, as a monotherapy, it's a supportive study for this label. So -- and it has also shown in the first week early outset mechanism of Plinabulin in multiple cancer types. So that study is basically complete to be the supportive trial. So we're not doing anything for that. Does this answer your question?

Yes. Any sort of publication strategies or presenting strategies for that trial? Or the focus is going to be on PROTECTIVE-2 going forward?

Okay. So for the label, I think the pivotal trial is PROTECTIVE-2, right? And then PROTECTIVE-1 is the supportive trial. And that's what Ramon just mentioned, the PROTECTIVE-1, the Phase II portion has been accepted in the major journals for publication in the coming months. And of course, for this Phase III study, we will also be planning for the publication as well. So you will see the result.

I see. Excellent. All right. That's helpful.

Okay. So Ramon can comment on the EAP, which is really very instrumental for Ramon to set this up, really just help cancer patients. Ramon?

Yes. So the EAP program is up. We already have 1 investigator, who approached us. And as you may be aware, we already have the first patient who was dosed with Plinabulin in the context of this EAP program. There, we continue to see interest. And we will, as we go, accommodate other investigators who have an interest in adding Plinabulin to G-CSF. The COVID-19 environment, as you know, has impacted the health care dynamics, which tends to be different from state to state. So we continue to have interest in this program. We continue to build this program to the benefit of the patient and medical community.

Okay. Great. So Rich, do you want to answer the revenue question?

Yes. So I think this is a really interesting question, so thanks for posing it. Andy, I think it's really timely. So we see this as an opportunity to, as Ramon alluded to, help address the concerns. Our market research -- we're in the midst of doing market research right now. So all the market research I referenced on my comments on the call were pre-COVID. And so we're doing market research right now to get a sense of how things might change in this environment. And actually, the concern has ramped up considerably. We see on the first 3 months of the pandemic, the number or the percentage of chemotherapy cycles has dropped by 20% to 40% depending on where you are in the country, and on average about 20% overall. Then that has recovered to a great deal, almost back to normal across the board. But that was really driven by the concern over exposing patients and putting them in an immunocompromised state. So our thought here was, let's get out there and let's be the good corporate citizen, and let's help physicians and help patients who are concerned. So it's not our intention to use this as a revenue driver. We don't see this being that broad-based. And so it's really more or less to just say, "Hey, here's a helping hand, should you need it," and we think there's going to be some opportunity here. And we also understand that if we do this from a revenue perspective, we're going to have to justify the cost based on -- what we charge based on the cost of goods. And I don't think there's any value in that for us in covering our costs because, obviously, the exposure that's there. So we really just have no interest in doing that. I think it's not good for us in the long run. I hope that's helpful.

Yes. Yes, that's super helpful. And yes, that's great from a visibility and potentially political standpoint. So maybe last question for Rich. There appears to be a price war going on in the biosimilar G-CSF field as new products come online. Just curious about your thoughts on that implication to the commercial launch of Plinabulin.

Sure. So this is one of the tailwinds that Lan alluded to in her commentary. When we talked to payers and it -- getting back to one of the questions I was asked earlier about the label, payers are excited about the opportunity to have multiple G-CSFs on the market, as you would expect. I mean that's not a surprise for anybody. And it's really important for all of us to realize that payers do see us as -- do see Plinabulin as unique and we'll treat it as such. They see the value that's created because it is the only product that can do what we said it can do, raise the standard of care, the only product on the market or in development. And so they say, "Well, we're going to treat it as such." So we're going to treat that way for formulary consideration and for contracting consideration, which is very favorable for us, first and foremost.

Secondly, it creates this opportunity. You see, the first 2 biosimilars launched at a list price of a 33% discount, the third one launched at 37% discount. And we all know that these drugs are reimbursed on average selling price, or ASP. And we've seen the ASP drop considerably for the first 2 products. There's not enough data for the third one. ASP has reported 2 quarters in arrears. So there was not enough data yet to see exactly what's happening, what the trend is with the third product. But the first 2 products, the lead product, its average selling price -- the first product that was launched rather, its average selling prices dropped by 22%. And the second product, which is actually the market leader, its average selling prices dropped by 18%. That's the latest data we have. So that's more indicative of what's actually happening in the contracting space.

And as that average selling price drops, the reimbursement for physicians and oncologists make their living based on ASP plus 4.5%, so this is hurting the physician. So we're looking at this opportunity as creating headspace for pricing. And when we talk about this with payers, payers are favorably inclined to that approach. We don't bring it up. We say, "What do you think is an appropriate place on the pricing continuum for it?" And the payers come back and say, "This looks like an appropriate place filling its headspace." So we're pretty excited about that because as you get more and more of these, the biosimilars have 2 choices. They can try and tranche the market and go for smaller and smaller slices, which doesn't seem very appealing, or they can play a price game, which, to us, we're agnostic. We want to play with everybody. So this is all favorable for us. So we're pretty excited about it. And we see payers taking greater and greater control over the biosimilars, which will again cause them to contract on a much more rigorous basis, which again will drive prices down, creating greater headspace. So we're excited about that. We think it's good for us. Does that help?

Yes, yes. That's very helpful. Thank you.

Thank you. We reached end of our question-and-answer session. I'd like to turn the floor back over to management for any further or closing comments.

Thank you, operator. Yes. This concludes our call today, and thank you, everyone, for your valuable time. Have a nice day.

Thank you. That does conclude today's teleconference. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.