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spk02: Good morning and welcome to BeyondSpring's fourth quarter and full year 2020 financial results conference call. At this time, all participants are in listen-only mode. Following management's prepared remarks, we will hold a brief question and answer session. To join the question queue, you may press star then 1 on your telephone keypad. Should you need assistance during the conference call, you may signal an operator by pressing star and 0. As a reminder, this call is being recorded today, April 30th, 2021. I would now like to turn the conference over to Andrew Erickson, Investor Relations. Please go ahead.
spk06: Thank you, everyone, for joining today's call. I'd like to advise listeners that comments made on today's call may reflect forward-looking statements that are related to such matters as BeyondSpring's clinical and preclinical research and development activities and results. regulatory and commercial plans, industry trends, market potential, collaborative initiatives, and financial projections, among others. While management believes that assumptions, expectations, and projections are reasonable in view of the currently available information, we 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 20F and other filings with the SEC, which are available on the investor section of BeyondSpring's website. Joining us on today's call is Dr. Lan Huang, BeyondSpring co-founder, chairwoman, and chief executive officer, Dr. Ramon Mohanla, executive vice president, research and development, and chief medical officer, Richard Daly, chief operating officer, and Elizabeth Serapak, chief financial officer. It is now my pleasure to turn the call over to Dr. Lan Huang. Lan?
spk04: Well, thank you, Andrew. Hello, everyone, and thank you for joining today's call. I'm very pleased to be here with an update of the tremendous progress we have made in 2020 and to provide an update on our upcoming milestones for 2021. 2020 was a truly momentous year in setting us up for future value creation. Specifically, we had key accomplishments in building clinical evidence for our lead asset, Pnebulon, filing NDA for our lead program in two major global markets, U.S. and China, building our pipeline, adding key scientific and business leadership, and bolstering our balance sheet to execute on our vision. Let me briefly share with you our three key areas for value creation. First, we continue to develop penicillin as a pipeline in the drug, not only as an agent to prevent chemotherapy-induced neutropenia or CRM, but also as an immune anti-cancer agent for potential durable anti-cancer benefit. For our lead program in the CRM prevention indication, penicillin and GCSF combination regime was granted breakthrough destination from both US and China FDA in September 2020. We're excited about this destination as this signals the severe unmet medical needs in CRN and that our regime could be superior to standard care. For the last five years, we have worked closely with regulatory agencies to advance benevolence in combination with CSSF for the prevention of CRN. We are also grateful to have the support of Dr. Blaney and Dr. Crawford USCIN, NCCN guideline founding member, and former chairman who have guided us for trial design and quality. Overall, we had over 1,200 patients in one pivotal trial, which is Protector 2, and five supportive clinical studies demonstrating benevolence-consistent early onset of action in protecting neutrophils in various chemo and various cancers in week one, where over 75% of clinical consequences occur, or the neutropenia vulnerability gap, a recognized severe unmet medical need. By combining penicillin's week one benefit with that of GCSF, including pacfew grassens with two benefits, the combination can maximize the neutrophil protection in the full chemo cycle. This combination's superior benefit compared to GCS alone was also confirmed in Protector 2, our pivotal global study with data released in November 2020. Based on that, we filed an NDA in the U.S. and China in March this year. And I'm now moving forward towards becoming a commercial stage company with a differentiated therapy that really has the potential to improve lives and clinical outcomes for millions. Cannabinoid and GCSR combination could potentially reduce the incidence and duration of fibroneutropenia and hostilization which we will present at upcoming ASCO meeting in June. With consistent improvement in clinically meaningful endpoints and ANC-based endpoints on the combination of cannabinoid and GCSF compared to GCSF long, we believe we can deliver on our promise of raising the standard care for CRM prevention in cancer patients treated with chemotherapy with or without checkpoint inhibitors. This is the first breakthrough in 30 years since GCSF was approved in 1991. Very importantly, 2021 will be a defining year where we expect to showcase benevolent anti-cancer efficacy data including top-line overall survivor data in the Dublin III study in mid-year. It took us five years to enroll all of 559 patients in approximately 60 centers in the U.S., Australia, and China. Dublin III compares penicillin and docetaxel versus docetaxel alone in second- and third-line non-small-cell lung cancer for EGFR-Y type patients, which compromises approximately 75 of Asian patients or approximately 85% of Western lung cancer patients. This is a severely unmet medical needs indication where TKI, tyrosine kinase inhibitors, do not work. And only four therapies have been proved with limited survivor benefit and severe side effects, such as over 40% incidence of severe neutropenia. In addition, we continue to round out penicillin's anti-cancer profile by adding it to the mix in triple IO therapies, as penicillin is a potent antigen presentation agent with potential synergy with checkpoint inhibitors and chemo or radiation, and help to revert PD-1 failed patients to resume responding to treatment. At upcoming ASCO meeting, we will release promising anti-cancer efficacy data on a phase one study of PNAVIN adding to NEVO and IPI in second and third line small cell lung cancer patients. who were checkpoint inhibitor naive or failed. This study included 10 U.S. leading clinical centers, and the BMS provided NEVO and IPI for free for the study. In addition, while conducting another IIIO combo study, penicillin adding to PD-1 or PD-L1 inhibitor and radiation at MD Anderson in seven cancers in PD-1, PD-L1 antibody-failed patients. Second, we are building out our pipeline in our subsidiary, Seed Therapeutics, using our unique molecular group targeted protein degradation, or TPD, platform. This platform demonstrated validation through our 800 million R&D collaboration with Eli Lilly in November 2020, including a substantial upfront payment and investment from Lilly. Currently, we are moving forward with Lilly's first target and our internal targets, including KRAS G12D. Third, On the business front, we have strengthened our board and management team and broasted our balance sheet to enable the execution of our vision. In 2020, we have added key scientific and business leadership to our board. In December 2020, Dr. Jeff Vesica joined our board. Dr. Vesica is a board-certified hematologist and oncologist and serves as CEO and Chairman of the Board of New York Cancer and Blood Specialists, and is a board member of One Oncology, which treats around half a million cancer patients a year in the U.S. His wealth of expertise and demonstrated ability to collaborate with different groups of stakeholders within the oncology market will be instrumental in helping guide the company as we seek commercial approval of Penabulin. We also added additional industry leaders in 2020 to our board. We added Dr. Ravi Majeti, Chief of Hematology at Stanford Medical School and a co-founder of 47. He is helping us in translating Penabulin's compelling scientific and clinical data into business value. as his formal company, 47, was acquired by Gilead for $4.9 billion. And Dr. Zabrowski was a veteran business development executive in large pharma, including formal global head of pharma partnering at Roche, where he led over 300 partnership deals. He has been helping us with business development and partnership strategies. And we are proud and honored to have a pharmaceutical and biotech veteran, Elizabeth Serapak, joining us last September as our CFO. Elizabeth has over 30 years of senior finance leadership, board, and venture capital experience in both large pharma, including Roche and Merck, and high-growth stage companies. Under Elizabeth's leadership, in November 2020, we successfully completed a financing of approximately $86.3 million in growth proceeds before deducting underwriting discounts and commissions and other estimated offering expenses. This financing strengthened our investor base and extended the cash runway by another 12 to 15 months. I will now turn the call over to Dr. Ramon Mahano, who will discuss our recent clinical developments in more detail. Ramon.
spk05: Thank you, Lan. First, I would like to provide an overview of the results of our registrational trials of the NAVLIN for the prevention of CIN. Over the last five years, we have advanced our CIN program, and as Lan indicated, it has culminated in our recent filing of an NDA to the U.S. FDA and China NMPA. We are very confident and optimistic about the success of our filings after lengthy, extensive interactions with regulatory agencies. who have proactively contributed to our study designs and reviewed all study protocols prior to enrollment. Filing has been a many months long preparation and includes data from the pivotal trial protective two, as well as other supportive trials, such as protective one, study 101, and Dublin three. We have collected data in more than 1,200 patients, of which more than 700 patients had been dosed with tenablin. We believe this represents sufficient data needed to satisfy the efficacy and safety requirements, as well as other sections as required by the NDA. We believe this collected data set provides very strong support for adding planabalin to PEC-Filberstim. By combining planabalin with PEC-Filberstim, we not only demonstrated superior CIN efficacy, but also superior safety and quality of life versus PEC-Filberstim alone. Planabalin has a complementary mechanism of action to GCSF and protects against CIN in the first week of the chemotherapy cycle. It has been well established that GCSF is not very effective in the first week of the cycle, which represents a treatment gap with significant unmet medical need. With the use of GCSF, more than 75% of all CIN-related complications occur during the first week of the cycle. GCSF, such as pacfilgofim, however, is very effective in the second week of the cycle. Therefore, it makes sense to add sunabdin to pacfilgofim in order to fill the first week void with using pacfilgofim alone. In recognition of the unmet medical need that still exists with pacfilgofim alone, the FDA granted the breakthrough designation to the plenabulin-pecfilcicum combination, with which we are targeting all chemotherapies and all non-myeloid cancers. Most recently, we presented top-line data from our Phase III study, Protective II, Study 106, with the plenabulin-pecfilcicum combination in breast cancer patients at the San Antonio Breast Cancer Symposium. The study met the primary and all key secondary objectives, demonstrating superior efficacy and safety of the flenabulin-pecfibrocin combination. We also demonstrated a significant benefit with profound neutropenia, a well-known risk factor for increased rates of infection, febrile neutropenia, and hospitalization, with specifically a 53% reduction in the incidence of profound neutropenia, a 50% reduction in the mean duration of profound neutropenia, and a 41% reduction in the odds of experiencing febrile neutropenia comparing to PECFIL with Simbolon. Blenabalin also has anti-cancer activity, that is currently evaluated in a number of phase one, two, and three cancer trials. The NAMLIN is currently being evaluated in combination with Dosexcel in Dublin 3, a phase three global multicenter clinical trial in the US, China, and Australia for the treatment of advanced non-small cell lung cancer with a measurable lung lesion. Approximately 50% of non-small cell lung cancer patients will have disease progression with a checkpoint inhibitor in first line, and thus will need a second line and possibly a third line treatment option. Those successful regimens currently dominate in second and third line non-small cell lung cancer. Our objective is to demonstrate that the prenatal and dosage cell combination has superior efficacy, superior safety, and superior quality of life over current second and third line standard of care. As a reminder, we showed a positive trend of an overall survival hazard ratio of less than 0.75 in our pre-planned interim analysis of Dublin III in around 150 patient death events. We have just recently completed enrollment and are now getting ready for database log and expect to report final top line trial results in mid-year. Regarding our other cancer trials, we plan to present initial phase one data on the planabin plus nivolumab plus epilimumab combination in small cell lung cancer at ASCO, and to advance this trial into phase two. We have also initiated a new triple combination trial with PD-1, PD-L1 inhibitors, plus planabin, plus radiotherapy in solid tumors. As for our early stage pipeline, we remain focused on advancing our preclinical candidates in triple combination settings. Taken together, we expect that plenabin's immune-enhancing anti-cancer activity, together with its CIN preventive effects, will position it to become a universal add-on to anti-cancer treatments in general. With that, I'll now turn the call over to Rich, who will discuss our commercial strategy. Rich? Thanks, Ramon.
spk07: Congratulations, Ramon, to your team for filing NDAs for benevolent in both the U.S. and China, a tremendous pair of accomplishments. This is a very exciting time for not only BeyondSpring, but also our future customers and their patients. We are thrilled to be turning our attention to the market and the opportunity to tell the story of unmet medical need in the CIN space. As we go forward with our discussion today, we'd like you to keep two key concepts in mind. First, penicillin plus GCSF has the potential to provide improved protection against CIN across all solid tumors and all chemotherapy regimens. Penicillin has broad applicability across cancer types and chemotherapy regimens. Second, penicillin is the only therapy that has the potential to elevate the standard of care in CIN. Chemotherapy is a large market. Each year, more than 650,000 patients receive chemo. With the recent NCCN guideline change recommending that high and intermediate risk patients receive prophylaxis for CIN, the addressable population has more than doubled to over 70% of the entire chemotherapy patient population. CIN remains the number one cause of chemotherapy regimen changes and top of mind for oncologists. GCSFs are the current standard of care and are used more than 1.4 million times each year in the U.S. However, as good as GCSFs are, they are not good enough. Penavalin in combination with GCSF has the potential to elevate the standard of care. Confident in the strength of our clinical data for Penavalin and the significant market opportunity we are advancing our preparation for commercial launch into the CIN market. To execute the successful commercialization of penicillin, we are focusing our efforts on three key initiatives. Number one, driving awareness of the unmet medical need for a neutropenia vulnerability gap. Number two, position penicillin with key decision makers. Number three, activating key accounts, and ensuring broad access and availability for patients. Let's begin with the unmet medical need, the neutropenia vulnerability gap. As I mentioned before, managing CIN is a top priority for the successful treatment of cancer. GCSS are good medicine. However, they are limited by their mechanism of action, as is vegan working about day nine or 10 after chemotherapy. As a result, GCFF are unable to manage CIN well in the early days post-chemotherapy. The first 10 days after chemo is the neutropenia vulnerability gap. That is, this is the time when neutrophils are at their lowest and patients have the highest risk of infection, febile neutropenia, ER visits, and hospitalizations. Seventy-five percent of all CIN-related life-threatening events happen in the first 10 days after receiving chemotherapy. CIN forces oncologists to modify cancer care. Light modifications can have a devastating impact on outcomes. Even with the availability of GCSS, between 30 and 50 percent of patients still experience significant dose delays or dose reductions of their chemotherapy. Dose reductions as small as 15% or dose delays of as little as 15 total days over four to six cycles of chemotherapy can result in a decrease in overall survival of as much as 50%. Only penicillin, with its unique mechanism of action as a selective immunomodulating microtubule binding agent, or CIMBA, can help manage CIN in the first 10 days post-chemotherapy, addressing the neutropenia vulnerability gap Only penicillin in combination with GCSF has the potential to elevate the standard of care in addressing CIN. Our second area of focus is in positioning penicillin with key decision makers. Our outreach is underway. Our disease awareness campaign, CINRest.com, and our presence at major medical meetings is building awareness. Our efforts through the website, CINRest.com, paid search, and educational outreach have resulted in 6 million impressions about the medical unmet need to date. Additionally, our publication strategy is bringing forward the clinical data supporting benevolence benefits. We are building our KOL support network through our educational council, a group of global experts in cancer care and CIN who are actively vetting our approach, messaging, and educational efforts. Finally, we are in the field meeting with national and regional decision-makers to drive a deeper understanding of the risks associated with CIN and the potential for improved prevention. Penavelin's unique mechanism of action as a selective immunomodulating microtubule binding agent, or CIMBA, has the potential to provide oncologists and patients with the additional protection against CIN, raising the standard of care. Cannabinol has the potential to provide significant benefits for providers, payers, and patients when combined with the GCSF. For providers and payers, cannabinol can help reduce the potential for infection, febrile neutropenia, ER visits, and hospitalization with the goals of reducing cost and improving control over patient care. Additionally, by avoiding CIN, patients may stay on chemotherapy at the right dose and on the right cycle time, giving them the best hope for a positive outcome in their cancer care and minimizing the risk of GCSF-associated bone pain. Let's move on to our third initiative, activating accounts. As I mentioned, our outreach is underway, and we plan to ensure broad access and availability to penicillin at launch and beyond. Oncologists are excited about the potential of penicillin, In multiple rounds of market research, each round with more than 100 U.S.-based board-certified oncologists, we've seen an overwhelming positive response to penicillin's profile and the potential for penicillin in their practices. In our most recent survey with more than 100 U.S. oncologists, more than two-thirds saw a role for penicillin in combination with GCSF in the prevention of CIM. More than three-quarters stated a high likelihood to use penicillin in combination with GCSF. Our intention is to bring penicillin to market as a therapeutic partner to GCSFs to elevate the standard of care for the benefit of cancer patients in need. We will work synergistically with oncologists who believe in GCSF therapy and who want more protection for their patients. As you saw in our market research, this represents the majority of oncologists. Concentration of use is a hallmark in the GCSF market, with over 80% of CIM therapy focused in 360 multi-center accounts. We believe that this concentration benefits our strategy of combination therapy and our focused efforts as an emerging company. A high volume of GCSF user believer is our main customer, and we have already identified these accounts. The majority of GCSF use occurs in four cancers, breast cancer, lung cancer, colon cancer, and pancreatic cancer. This dual concentration of business, that is account and cancer type concentration, enables BeyondSpring to target our efforts through effective and efficient commercial efforts for optimal benefit to patients, providers, payers, and shareholders. Consequently, our commercial structure can be lean and highly targeted. A critical element of PNAVLA success will center on our availability and access to patients in need. We are on track for commercialization, and our focus is now on developing our systems to ensure appropriate access. These include targeting rapid inclusion of PNAVLA in key therapeutic guidelines, immediate filing for a permanent JCODE, focused selling into clinical pathways that drive the utilization of drugs in larger oncology practices, outreach to payers and GPOs to ensure appropriate pre-approval awareness, and targeted contracting for optimal coverage after launch. Developing our patient services hub, including patient assistance program and dedicated field reimbursement specialists from launch until the assignment of a permanent J-code. As mentioned, Earlier, all of these efforts will be supported by a highly effective and efficient commercial team armed with state-of-the-art promotional tools and programs focused on oncologists who believe in the benefits of greater control over CIN. In summary, we are excited by the demonstrated clinical profile and potential of Penavelin. Moreover, we remain excited by the market opportunity. The market is large, robust, and expanding. The unmet medical need is real. The neutropenia vulnerability gap can, for the first time, be addressed due to Penavelin's unique SIMBA technology. Penavelin paired with GCSF has the potential by keeping ANC, or absolute neutrophil count, out of the danger zone and reducing CIN to keep patients on their prescribed dose and their cycle times on time. Our market research indicates that payers will cover Penavelin and oncologists intend to use penavalin in combination with GCSF because of the potential benefits penavalin brings to patient care. In short, we're excited. We think the opportunities are fantastic. With that, I'll turn over this session to Elizabeth. Elizabeth?
spk03: Thank you, Rich. I will now briefly discuss our fourth quarter and full year 2020 financial results. For greater detail related to these results, I refer you to our press release issued this morning and to our 20F 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 financial results. Research and development expenses in the fourth quarter of 2020 were $8.4 million, compared to 12.6 million in the same period last year. The decrease of 4.2 million was primarily due to a decrease of preclinical and clinical trial expenses. General and administrative expenses were 10.4 million in the fourth quarter of 2020, compared to 2.7 million for the same quarter of 2019. The $7.7 million increase was primarily due to an increase of $3 million in employee salaries and benefits, including new hires and one-time bonuses relating to a transaction, an increase of $2.6 million in pre-commercialization expenses, an increase of $1.8 million in non-cash share-based compensation, and an increase in legal and other costs related to the seed subsidiary. Net loss attributable to Beyond Spring Inc. in the fourth quarter of 2020 was $17.6 million compared to $14.1 million for the same period last year. R&D expenses were $41.8 million for the year ended December 31, 2020, compared to $31.3 million for the year ended December 31, 2019. The $10.5 million increase was mainly due to an increase of $3.8 million in clinical trial expenses an increase of $3.5 million in non-cash share-based compensation, and an increase of $2.7 million, mainly due to amounts paid to consultants and others to support the NDA filing. G&A expenses were $22.6 million for the year ended December 31, 2020, compared to $9.0 million for the year ended December 31, 2019. The $13.6 million increase was primarily due to an increase of $5.6 million in pre-commercialization expenses, an increase of $4.5 million in salaries and benefits for commercial and executive personnel, and one-time performance bonuses related to the closing of a transaction, an increase of $2.6 million in non-cash share-based compensation, and an increase of $.9 million in consulting and other professional services. Net loss attributable to Beyond Spring, Inc. was $61.0 million for the year ended December 31, 2020, compared to $38.1 million for the year ended December 31, 2019. As of December 31, 2020, we had cash and cash equivalents of $109.5 million on hand. The company believes it has sufficient cash to support its ongoing clinical programs over the next year, including its immuno-oncology pipeline and to prepare for a potential launch of Plenabulin in 2022. With that, I'll now turn the call back over to Lan to conclude. Lan.
spk04: Thank you, Elizabeth. We are very proud of the accomplishments we had in our extremely productive 2020 to set us up well for value generation in 2021. were well-positioned for the future with our pipeline in the drug, Penabalin, already filed NDA in CRM prevention indication with anticipated near-term potential anti-cancer efficacy data from a phase III, doubling III study measuring overall survivor in non-small cell lung cancer patients. And from early trials in several IO regimes, in checkpoint inhibitor naive or failed patients. After the successful completion of our equity financing in the fourth quarter, we have strengthened our balance sheet as we head into our upcoming milestones. Here, I would like to thank the patients, our dedicated team, our shareholders, and our partners for their continued support as we work towards improving the current standard of care for cancer patients worldwide. I will now ask the operator to open the call for question and answer session. Operator.
spk02: Thank you. We will now begin the question and answer session. To join the question queue, you may press star then 1 on your telephone keypad. You'll hear a tone acknowledging your request. If you are using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press star, then two. We will pause for a moment as callers join the queue. Our first question comes from Maury Raycroft of Jefferies. Please go ahead.
spk01: Hi. Good morning, everyone, and congrats on the progress, and thank you for taking my questions. First one is just a quick one on the Dublin data readout expected mid-21. Just wondering if you can say if you submitted a placeholder for a late-breaking abstract at ASCO, or could we expect to see a press release around ASCO?
spk04: Thanks, Maury. This is Lan. Thanks for your continuous support. Yeah, so we don't have the Dublin Street data yet, and the late-breaking, the finish time was March, at the end of March. So the answer is you will not see any data from Dublin 3 in the ASCO meeting. Well, guiding the market is mid-year.
spk01: Okay, okay. And then for the ASCO titles that posted and the data you're going to have there, just wondering if you can elaborate on what additional analyses you'll show beyond the top-line Protective 2 Phase 3 CIN data.
spk04: Thanks for the great question. So for the protected two, everyone would love to see the clinical meaningful endpoint correlation with the ANC-based endpoint, which we show very high statistical significance. So in the ASCO coming up presentation, we are going to show additional reduction in FN and hospitalization, those type of clinical meaningful endpoint for the protected two for combination treatment versus Pacfield, Glass, and Long.
spk01: Got it. And will there be anything on bone pain, dose intensity, or quality of life?
spk04: So probably I should give this to Ramon on the bone pain and other quality of life standpoint.
spk05: Ramon? Yes, yes, we have. Yes, thank you for the question. Yes, we have an abstract accepted on quality of life as well with the combination, Planabrin plus Paxilvisin versus Paxilvisin alone. And, yes, we have other overall safety that includes bone pain as well. That's correct.
spk01: Got it. Okay. And just a last question on Paxilvisin. Just wondering what the latest is that you're hearing from payers regarding launch price in light of the positive Phase III CIN data alone or launch price that can also be supported by positive Dublin Phase III data showing the anti-cancer benefits. I guess how do you think about those two situations from the value of having the two different modalities translating to price of the drug?
spk04: Well, thanks for this fantastic question, Maury. I think this question, the best answer is from Rich.
spk07: Thanks, Maury. So our market research continues to show that on its own, the CIN benefit in combination with GCSF, as I said on the call, is robust. They like the profile. They like the opportunity to reduce the neutropenia and the potential for reduced febrile neutropenia, emergency room visits, hospitalization, et cetera, and keep the patients on their chemotherapy. So they like that on its own. The response to the potential for improvement in cancer outcome in and of itself, I think, is an additive. And, you know, they're looking for we think we would have improved pricing power with that. So we see a really strong response, a favorable response on price. because of the profile of the product in and of itself with CIN. And then, obviously, should the data bear out with Dublin 3, we think we have an opportunity for greater value creation for patients, for payers, and obviously for providers. So we'd love to, you know, be able to bring that forward.
spk01: Got it. That's helpful. Thank you for taking my questions.
spk02: Thank you, Mari. Our next question comes from Jason Gerberry of Bank of America. Please go ahead.
spk09: Hey, good morning, guys. Thank you for taking my questions. I guess the first one for me is just trying to think about how you're thinking about launch readiness, particularly in a scenario where you get accelerated review and could be in a position to launch in the second half of this year, and thinking about that versus the cash and cash burn commentary. Obviously, I can appreciate that it's a fluid situation, but just kind of curious how you're approaching things in given cash considerations, and are you hiring reps on a contingency basis? And then as we think kind of longer term with the rollout, is it fair to look at sort of standalone one-product cancer biotech companies like Exelixis as a good comparable for SG&A build-out for you guys and your story?
spk04: Well, thanks, Jason. Yeah, this is a very key question. As we finish the successful NDA filing in the CI indication, also based on the breakthrough definition of the regime, so potentially the NDA approval is coming soon. So that is a key question on the commercial readiness for us. So Rich and his team has been working tirelessly on this effort. So I'm going to turn the baton to Rich to answer your great question.
spk07: Yeah, this is a fundamental question for us. And we look at the timing of the approval, and we also look at what we want to do and be judicious with our resources. So to your question about are you hiring on a contingency basis, so we want to be sure that we have an approval. We want to be sure that we can go forward. And then we want to integrate that with the structure of the P&L. So we believe, going back to Maury's question, we believe that we're going to have a favorable price. We love the structure of this P&L. Because, again, as I said on the call, we think that this can be a highly targeted launch. We know exactly where the accounts are. We know who the physicians are who like the GCSF profile and want more control. So we think it can be really targeted in our approach to the market. The question of timing is a really interesting one. Launching a product late in the year when you get into the holidays is always a dicey proposition. If you look at Coherence as an example, they got approval in September and waited to launch into January. I think that's probably a wise decision because going into the holidays is never a good thing, and the 10 or 12 launches I've done, you never really want to be launching late in the fourth quarter. You just can't get anybody's attention, and you really want that attention in the first 13 to 20 weeks of launch. So, you know, the timing of it really matters. On a contingency basis, we think we want to be sure we have the launch, so we're going to hire. We will be out interviewing. We will be ready to pull the trigger when we get the approval. So we will have identified all the sales representatives we want. We will make the offer on approval. We will bring them on board. So we will not be carrying those costs at risk. We think that's important. But as we work our way down the P&L, we think we'll get a very solid price based on the value we'll be delivering to the marketplace. The cost of goods are very, very small here because this is a small molecule, three-step synthesis. And the cost of sales, again, very lean. So we think that this is a really solid model, and we think the company can move forward appropriately, aggressively with one molecule in its bag and be very successful. So we're really excited about that. So we think there are other models out there that you can look at and say, yeah, this is a good one to peg off of and build a, P&L for BeyondSpring.
spk09: Great. And then just, you know, obviously the next big topic for you guys, Dublin trial and top line. Will we get ORR and PFS data as well with the top line update? And the reason I ask is we've seen some data for second line IOTKI agents and, you know, obviously the markets are going to want to compare your results to those approaches that we've seen some data in And we don't have OS data for those approaches yet. So just wondering what we'll have at our disposal to start to make those cross-shot comparisons.
spk04: Yes, and thanks for this great question. So W3, you know, we don't have the data yet, right? So as the, you know, data is coming, then we will decide, you know, how to present this data at the right time. But I do see your points. For comparison purposes, probably it is also very important to show the ORR and the PFS, but of course we have to make sure the data is clean before we show it.
spk09: Sure, sure. Okay. Yeah, just I guess as a commentary for us, at least in the markets, how we're going to start to look at that data. And then I guess last one for me, just ahead of ASCO, you just remind me the rationale. I know this was an investigator-sponsored trial, but the rationale for small-cell lung, I think PD-1, A CTLA-4 combo had failed in this setting before. So I know that there's sort of a broad-based IO combination strategy here, but your thoughts and rationale for small cell. That would be helpful. Thanks.
spk04: Yeah, thank you. So I think I should turn this question to Ramon to start. Ramon, I think you have instrumentally started this small cell lung cancer study based on penicillin's immune benefit.
spk05: Yes, thank you, Lan. So the rationale for adding plenablin to nivolumab and ipilimumab in small cell lung cancer is that small cell lung cancer was indicated for nivo and ipi on the NCGN guidelines for a very long time. So doctors used that combination. We are interested in adding planabin to existing IO regimens to demonstrate that planabin would bring a tremendous benefit on top of those IO regimens. So that combo being available through the NCCN guidelines was sort of the vehicle to add planabin to that. The objective clearly is for us to show that we have additional survival benefits with adding planabin, but also that planabin will prevent the immune-related adverse effects. You will be aware that with immunotherapy, especially with combination PD-1 and CTLA-4 inhibitors, The biggest reason, not one of the reasons, but the biggest reason for treatment discontinuation is immune-related adverse events more than 30% of patients. So we added Clonabin to this regimen. We hope to see not only a survival benefit, but also a reduction in immune-related adverse events. So that collectively became the rationale.
spk04: Yes, thank you. Yeah, so actually I just want to add one more item to Ramon's thinking. So why is this IIIO combo not only looking into the safety benefit, immune AEs, but also the efficacy benefit, which is the response rate in addition. But as you see, for the second and third line, small cell lung cancer treated with checkpoint inhibitor, Its response rate is between 12% to 18%. So if we can see better ORR than that, that definitely is going to, you know, speak for cannabinoids' immune benefit. But very importantly, for the study, we'll also enroll patients who failed checkpoint inhibitor, right? So if we can resensitize the system with penicillin adding to this checkpoint inhibitor combination, that's going to answer a lot of the unmedical needs for the checkpoint inhibitor failed patients. So this is a very important presentation, so I hope you guys will stay tuned and look for this abstract and also the presentation later in June. Thank you.
spk01: Thanks, guys.
spk02: Our next question comes from Andy Hisse of William Blair. Please go ahead.
spk08: Oh, great. Thanks for taking my questions and congratulations on all the progress, especially a very stellar 2020. So I have a question for Rich. Actually, I'm happy to report to Rich that CINrich.com, it actually showed up on my personal Twitter. So congratulations on a very successful, you know, outreach campaign. So the first question is kind of, you know, Rich, as you think about this CIN indication, how would you characterize as kind of the breakdown between commercial pay and Medicare, Medicaid pay? And also, I am curious to know about your perspective as you think about, you know, reimbursement discussions with a hospital. How would you use it? hospitalization endpoint that's going to be presented at ASCO to kind of leverage your strategic positioning?
spk07: So, Andy, great questions. So when we think about, we look back on historic norms for GCSF utilization. So, again, we're partnered with the GCSF to elevate the standard of care. So we look at how GCSFs are used, and this is a fundamental question for us. So, you know, everybody talks about, are you going to be covered? What's your pay coverage and all that? So J codes become really important, temporary J codes. Today, about 50% of GCSF use is covered by Medicare and Medicaid. And that's most recent data, which is about 2018, roughly about 2018. So this is predominantly an elderly population, which makes sense. Cancer predominantly over the age of 65. That totally makes sense, right? So when we look at that, we're going to have coverage from day one. Bylaw will have coverage. So, you know, we're excited about that. And then it becomes the question of, you know, driving the opportunity. And this is where we get into the three things we talked about on the call was driving that neutropenia vulnerability gap, helping people understand that unmet medical need, talking about the positioning for the product, and then a key account activation. And key accounts not only are the community oncologists, but also the hospitals that you talked about. So, you know, looking at the split between those as well. And predominantly the use of GCSF, and we're talking about pegylated GCSF because one dose equals one cycle. Non-pegylated, sometimes one dose, obviously those are daily. You get one, you get four, you get seven, you get ten. It's hard to equilibrate the dose. So predominantly non-pegylated are hospital-used, it's the hospital-used dose, if you will. So you see the predominant use of the peglated in a community opportunity. So we're really focused our efforts there and in helping those physicians understand how to avoid that hospitalization, right? Because, again, we're elevating that standard of care and we can keep that patient away from profound neutropenia, keep them away from that febrile neutropenia and out of the emergency room. We're going to be focused on cost reduction and keeping that patient on their therapy and then avoiding you know, the dose changes for chemotherapy and improving that standard of care. So we're looking at, you know, our focus is where we can make a difference. Obviously, we think we can make a difference in the hospital setting as well, but we think that might be a little bit further down the line. So we're going to really be targeted in our effort, again, where we can drive that difference. Is that helpful?
spk08: Yeah, that's very helpful. Thank you. I look forward to that discussion in the future. So I guess this is a question for the team. I think I, if I remember correctly, I think Elizabeth kind of provided the guidance that the launch will likely happen in 2022. So I just wanted to make sure that, you know, Rich, I think you kind of said that, you know, even in the event of approval, you might want to kind of wait until the early part of next year to launch. Is that correct? You know, I'm just kind of asking that from a modeling perspective.
spk07: I think it all depends on the timing of the approval. So I gave the coherence example only to give a framing for it, you know, because if we're going to wait to hire our folks so, you know, we don't have to give them the offer, they have to accept, they have to give notice, et cetera, we have to train them, So you're talking about a month or maybe more before they can actually get on board. And then you're into, depending on when we get the approval. So it all depends. And so we're just trying to help everybody understand how we're thinking about it. We don't want to take on that untoward risk of hiring a full team and then waiting. We don't think that's appropriate to do. But we also don't think it's appropriate to launch, you know, just prior to Thanksgiving. That just wouldn't be effective. It just wouldn't work. In my experience, those are very difficult times to get anybody's attention in any marketplace. So, you know, I hate to play the NBA here, but it all depends on when we get the approval. Given that we, you know, file at the end of the first quarter or we submit at the end of the first quarter and, you know, we're looking for the submission to be accepted, right, 60 days later, it's just you start thinking about the timing of when that six-month, if it was a priority review, when that might come, we start talking about, if we were to get that priority review, we start talking about you're right on the bubble there. So, again, we're just trying to set that expectation that it's probably a 2022 opportunity. So, does that make sense?
spk08: Yeah, yeah, for sure. And then, I guess, lastly, for – thank you – for Lon, it
spk03: Your question is cutting out, Andy.
spk07: Andy, are you there?
spk02: Andy, your line is live. This concludes the question and answer session. I would now like to turn the call over to Dr. Huang for any closing remarks.
spk04: Thank you again for everyone to participate in today's call, and thank you for your insights and great questions, and also your continued support. So we look forward to keeping you updated on our significant milestones to come this year and beyond. Thank you. Have a nice day.
spk02: This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.
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