BeyondSpring Inc. (NASDAQ:BYSI) Q2 2020 Earnings Conference Call September 3, 2020 8:00 AM ET
Scott Eckstein – Vice President at KCSA Strategic Communications
Lan Huang – Co-Founder, Chairman and Chief Executive Officer
Ramon Mohanlal – Executive Vice President, Research and Development and Chief Medical Officer
Richard Daly – Chief Operating Officer
Edward Liu – Chief Financial Officer
Conference Call Participants
Maury Raycroft – Jefferies
Joe Pantginis – H.C. Wainwright
Andy Hsieh – William Blair
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 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 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, 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 assets, first-in-class agent Plinabulin in late stage developments in two 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, three preclinical I/O agents, and a world-leading targeted protein degradation, TPD, platform to fuel future growth. Dr. Hershko, Nobel Prize winner in the field is our scientific advisor.
Finally, we have developed global capabilities to 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 U.S. FDA by the end of 2020. We have initiated rolling NDA submission for China NMPA in quarter one 2020. CIN indications have only one 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 is still experiencing over 80% of Grade 4 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 downgrades chemo regime in later cycles, all of this affect chemos anti-cancer benefit. Therefore, CIN is still a severely unmet medical need.
Since our first IND meeting with the U.S. FDA 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 four-year journey, Dr. Blaney and Dr. Crawford, U.S. CIN and NCCN guidelines Founding Member and former Chairman, have been guiding us for the trial design and trial quality.
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; sustain 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 details clinical and the preclinical achievement in the second quarter of 2020. First, the positive top line pre-specified interim Phase 3 data from our PROTECTIVE-2, a 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 all chemo and all myeloid cancer in the last 30 years.
I’m also excited to report to you that the moment of a total of 221 patients in 106 Phase 3 study has been completed in July ahead of schedule, and we expect top line Phase 3 data will be available in quarter four 2020.
Second, our DUBLIN-3 trial [a 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 3 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 needs indication as only four 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 thing in two interim analysis is expected, justified by Plinabulin’s I/O mechanism in activating immune defense protein GEF-H1 and the positive Phase 2 subset analysis based on mechanism targeted patients. We look forward to the final top line data for first-half of 2021 at 439 staff 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 non-responsive tumor models conducted at MD Anderson.
We plan to start a triple I/O and Plinabulin combo study at MD Anderson in second-half 2020, with the intention to reverse progressive disease of previous PD-1 antibodies failed patients. This potential success of the study were showcased 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 the drug for multiple cancer indications.
Finally, we believe the foundation for an innovative company is patents and talents. 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 the drug. And for our company, we 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 top 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’re 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 five 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 fiscal 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 design and refute all our protocol prior to enrollment. We have had in-depth discussions with the FDA regarding changing the primary endpoint from DSM to the more meaningful endpoint of rate 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 DSM. 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 two drugs are complementary to each other, where Plinabulin predominantly provides protection in the first week of the cycle and pegfilgrastim predominantly in the second week of the cycle.
Combining these two agents provide superior care and protection compared to each of them alone. Together, these two agents also come with a more favorable safety profile. Hence it would make sense that every time an oncologist describes pegfilgrastim or G-CSF, they should consider adding Plinabulin to that. The indication we are targeting is very broad to include all chemotherapy 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 collective 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 pre-planned interim analysis, wherein the DSMB not only reviewed the safety data in an open session, but also the efficacy data in the closed session to the term and benefit risk of the Plinabulin dose cell combination.
Based on their review, the DSMB recommends the trial to continue without modification. We feel that is very positive and are currently moving ahead with completing patient enrollment, which we expect will occur this year. Just as all pharmaceutical companies, COVID-19, this impact and continues to impact our timelines. 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 best 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 anti-cancer mechanism of release in GFH-1, as we validated in the cell reports paper.
Second, in our Phase 2 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, and the first pre-planned interim analysis of the Phase 3 trial, 103, is 150 patients best event. We showed a positive trend of an OS of HR less than 0.75.
Fourth, 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 regimens.
With the current standard of care in second and third-line, we achieved improved survival. However, at the expense of safety, this more toxicity and an expensive quality of life. With Plinabulin docetaxel combination, not only do we expect superior frequency of docetaxel alone, but also have reduced toxicity and have 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 the checkpoint inhibitor regimen in first line. And this will be a need of a second-line treatment option. The Plinabulin docetaxel combinations 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 non-myeloid cancers Plinabulin docetaxel combination strategy and we envision that Plinabulin will be added to pegfilgrastim or G-CSF every 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 were currently G-CSF is not indicated for use or is listed in the warnings and precautions 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 strategy 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 has presented at the AACR 2020. Currently, preparations are on the way 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 efforts. 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 healthcare systems to meet the challenges that have been imposed on them by the current COVID-19 environment.
We have initiated a broad outreach and awareness efforts with Plinabulin 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 the 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 2 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 CIM NDA application this year and the non-small cell lung cancer NDA application next year. In support of our commercial preparation, we have initiated the broad medical affairs with an outreach and awareness effort 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 potential role that Plinabulin can play 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 three elements that drive our excitement. First, the unmet clinical need; second, the changing market forces in oncology; and third, Plinabulin’s commercial strategy for 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 GCSF given each year, the CIN market remains an unserved market. CIN is the number one 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. Three quarters of oncologists said, it was very to extremely important to prevent CIN. Monotherapy G-CSFs 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 three 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 four Ds.
As you heard earlier, this is the clinical profile and have one. Oncologists want a therapy that helped – that can help them provide more consistent, sustained chemotherapy. Our goal is to provide them with the tools to flip the four Ds to the four S’s to improve 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.
The vast majority of oncologists 74% are enthusiastic about a 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 two-thirds 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 favored Plinabulin’s introduction in 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 accounted 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, all adhering to evidence based guidelines. Clinical pathways have the potential to improve the effectiveness and efficiency of care. The majority of practice is based on 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 ontology.
So, how did these factors help us build a Plinabulin strategy? Based on the clinical data we generated, our market research and current oncology market trends we believe at Plinabulin, a medication and 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 will likely 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 costs of sales. We’ve already initiated our pre-launch 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 five core components. First, we’ll be deriving 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 and ferreting CIN. Based on this, we believe we are well positioned for inclusion in updated NCCN guidelines. 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 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, oncology had a very favorable response, 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-CSFs and payers indicate that they were treated as such in contracting and formulary discussions. To ensure appropriate reimbursement, we plan to launch a field reimbursement liaison team from day one.
Finally, healthcare practitioners and patient commercial support. Over the next year leading up to and through launch, we will deliver our fully integrated market preparation and launch programs for 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 pre-launch 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, will deliver launch support to drive rapid appropriate uptake of Plinabulin and this would include 60 to 80 sales 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 one, 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 to the oncology community bode well for this 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’ll 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 pre-launch 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 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 immune 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 the gross proceeds 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 continue clinical and preclinical development and for general corporate purposes.
With that, I 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 healthcare 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 catalyst. 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.
Thank you. [Operator Instructions] Our first question today is coming from Maury Raycroft from Jefferies. Your line is now live.
Hi, good morning, everyone and congrats on the progress, and thanks for taking my questions. I guess first question is just on the – if you could talk more about the NCCN guidelines submission prep for CIN, any thoughts on timing and 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 and reimbursement.
Yeah, thank you so much, Maury, for this great question. I think I’ll let Rich to start and then 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 two page application. So, very straightforward. And you can apply up to six 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 scheduled meeting is in the middle of October. So, as Ramon talked about, we, you know, 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 main 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 timelines 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 is again on their website is 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 they will – 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 seeing a blocking therapy. They want to be sure that they’re seen as very patient friendly, especially with something as devastating as cancer. So, it’s obviously a very sensitive situation with cancer. So we can’t really address each payer or the payer space in total, prior to approval. So that’s just 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 timeline shifts are related to COVID versus that event rate or other contributing variables?
Yeah, so probably I can start and then Ramon can add additional insights. So yeah, actually COVID-19 does impact in, you know, the timeline, right because, you know, everybody gets affected, but I think it is minimal things we are doing global enrollment, and also just for China, I think after March, everything seems to 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 patients best events, which is the full event, is going to be expected for first half of next year. And we’re closing almost at the end of the finishing of the enrollment, the 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?
Yeah, 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 hearing from the Plinabulin profile and also what’s the missing link for the G-CSF we do 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, you know, and TIN is a bone marrow problem, right? So, and from all the literature, if you look at it, even with the use of G-CSF well 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 9 or day 9, right. And Plinabulin 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 two 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 about similar 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’re using in the clinical study. So that’s a long answer. So, I don’t know if I answer your question.
No, it’s helpful perspective. Okay. Thanks for taking my questions.
Yeah, thank you.
Thank you. Our next question today is coming from Joe Pantginis from H.C. Wainwright. Your line is out live.
Good morning, everyone. Thanks for taking the question and thanks for all the color thus far, especially, you know, coming up ahead of very nice catalysts 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 3s or the Phase 3s are winding down, so you’re going to have a significant drop in clinical trial cost there, but then, you know, are we anticipating any significant boosts 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 three 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 headcount 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.
Perfect. Thanks for that color.
Thank you. [Operator Instructions] Our next question today is coming from Andy Hsieh from William Blair. Your line is now live.
Oh, excellent. Thanks for taking my questions. 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 it’s an 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 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 the end of 2018 showing that we did beat the statistical significance for the primary endpoint ensuring the DSN non-inferiority for Plinabulin versus Neulasta alone.
So, these things we are going forward with the combination label for Neulasta and Plinabulin. So for the PROTECTIVE-1 as a monotherapy, it’s a supportive study for this label. So – and it has also shown the first week early onset 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?
Yes. So for the label, I think, the pivotal trial is the PROTECTIVE-2, right? And then PROTECTIVE-1 is a supportive trial. And that’s what Ramon just mentioned, the PROTECTIVE-1, the Phase 2 portion has been accepted in the major journal for publication in the coming months. And, of course, for this Phase 3 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. Thank you.
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 one 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 assess 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 healthcare dynamics, which tend 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.
Yes. Okay, great. So, Rich, you want to answer the revenue question?
Yes. So, I think this is a really interesting question. So thanks for posing in. Andy, I think it’s really timely. So, we see this as an opportunity to, as Ramon alluded to, 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 the – 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 three months of the pandemic the number for the percentage of chemotherapy cycles has dropped by 20% to 40%, depending on where you are in the country, and then on average about 20% overall, that has recovered to a great deal almost back to normal across the board, but that was really driven by the concern overexposing patients and putting them in an immunocompromised state.
So, our thought here was let’s get out there, and let’s be a 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 it as 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.
We also understand that if we do this, and 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. 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 talk to payers and it gets 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 – 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 could raise the standard of care, the only product in – 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 two biosimilars launched at a list price of a 33% discount. 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 two prices, not enough data for the third one yet, ASP is reported two quarters in arrears.
So there’s not enough data yet to see exactly what’s happening, what the trend is with the third product, but the first two products, the lead product, its average selling price, the first product that was launched rather, its average selling price has dropped by 22%. And the second product, which is actually the market leader, its average selling price has 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%. This is hurting the physician.
So, you know, 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, you know, 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. And so it’s headspace. So, we’re pretty excited. about that because as you get more and more of these, the biosimilars have two choices, they can try and tranche the market and you 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.
Sure. Thank you.
Thank you. We’ve reached the end of our question-and-answer session. I like to turn the floor back over to management for any further closing comments.
Thank you, operator. This concludes our call today and thank you everyone for your valuable time. Have a nice day.
Thank you. It 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.