Good morning. Welcome to the BeyondSpring's first quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief question-and-answer session. As a reminder, this call is being recorded today, June 16th, 2021. I'll now turn the call over to Ashley Robinson of LifeSci Advisors. Please go ahead.
Thank you everyone for joining today's call. I would like to advise listeners that comments made on today's call may reflect forward-looking statements that are related to such matters as BeyondSpring's clinical and pre-clinical 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 the call for a variety of reasons, including those described in the forward-looking statements and risk factors section of the company's 20-F and other filings with the SEC, which are available on the Investor section of BeyondSpring's website. Joining us on today's call is Dr. Lan Huang, BeyondSpring's 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 Elizabeth Czerepak, Chief Financial Officer. It's now my pleasure to turn the call over to Dr. Lan Huang. Lan?
Thank you, Ashley. Hello, everyone, and thank you for joining today's call. It has been a very short time since we last spoke with you on our comprehensive year-end earnings call. I will keep today's remarks brief, but I would like to take time to highlight the key activities and continued progress as we keep moving towards commercializing and developing our lead asset, first-in-class agent, plinabulin, as a pipeline in the drugs for CIN prevention, non-small cell lung cancer, and potentially many other cancer indications. In this past quarter, U.S. FDA filed our NDA filing, and we have an anticipated PDUFA date set with the agency of November 30th this year. We were very pleased and grateful to receive priority review from the agency.
Priority review is granted by FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to the standard of care. We, of course, believe that plinabulin meets this definition and look forward now to our November PDUFA date. As we await our PDUFA date, we have made progress in developing plinabulin as a direct anti-cancer treatment agent in the global phase III non-small cell lung cancer study, or DUBLIN-3, and various checkpoint inhibitor combination studies in seven different cancers. In the coming months, we are looking forward to further validating plinabulin's direct anti-cancer ability with top-line overall survival data from our DUBLIN-3 study in non-small cell lung cancer. This phase III registration trial being conducted globally in 60 clinical sites, has finished enrollment of 559 patients.
It is designed to evaluate plinabulin in combination with docetaxel in patients with second and third-line non-small cell lung cancer with measurable lung lesions and EGFR wild type, which is around 85% of Western lung cancer patients. This is a severely unmet medical need indication as only four therapies approved with limited survival benefits and severe side effects, such as severe neutropenia in docetaxel-based therapies. This study has achieved two successful interim analyses. If a positive result in this study is achieved, we would anticipate seeking FDA approval and moving towards commercialization in this second indication for plinabulin. In addition, resistance to immunotherapy is a severe unmet medical need, and we believe plinabulin may have a potential synergistic anti-cancer effect when combined with checkpoint inhibitors.
First, our vision of developing plinabulin as a treatment in oncology is supported by the compelling data our scientific team presented at the recently concluded ASCO conference. At ASCO, we presented phase I data that showed plinabulin in combination with nivolumab and ipilimumab had 46% ORR in 13 patients with PD-1, PD-L1 naive or resistant tumors in second-line and beyond in small cell lung cancer. Additionally, the data showed that plinabulin combination was able to re-sensitize tumors that had progressed on prior PD-1 or PD-L1 inhibitors in third-line small cell lung cancer with 43% of ORR. The three PR patients in PD-1 resistant patient population had tumor reduction over 50% and a long duration of treatment, with one patient treated for 18 months.
Second, we have initiated an investigator-initiated phase I-B/II trial evaluating the safety and tolerability and efficacy of plinabulin in triple combination with both PD-1 or PD-L1 antibody and radiation therapy in seven advanced cancers who failed PD-1 and PD-L1 inhibitors at MD Anderson. The first patient was dosed in lung small cell lung cancer who failed Keytruda in early June. I'm very proud of our team as they tirelessly execute on this program. All of us are committed to raising the standard of care for cancer patients in the largest global markets with first-in-class treatments. We now draw closer than ever to achieving this mission and look forward to advancing plinabulin and realizing upon our many opportunities to succeed. I will now turn the call over to Dr. Ramon Mohanlal for a very important announcement of our upcoming R&D Day event. Ramon.
Thank you, Lan. I'm very pleased to announce that we will be hosting an R&D Day planned for Friday of next week, June 25th at 8:00 A.M., where we will be sharing with you our anti-cancer development strategy for plinabulin. Our event will feature presentations from Dr. Steven Lin, PI for the immune combination study from MD Anderson, and Dr. Trevor Feinstein, our DUBLIN-3 study PI from the Piedmont Cancer Institute. Our team will also present a more detailed overview of our program. Plinabulin is a first-in-class agent with a unique mechanism of action with selective binding to tubulin, and therefore releasing the broad immune defense protein, GEF-H1. This novel mechanism of action has been greatly de-risked through strong animal data and strong with preliminary efficacy data in small cell lung cancer patients that was recently presented at ASCO.
Data on this mechanism of action has also been published in peer-reviewed journals. Of course, we are known as a company that developed an innovative CIN approach with combining the non-G-CSF agent plinabulin with G-CSF, and we are very happy with that image. We now increasingly would like to direct our attention to the anti-cancer applications of plinabulin, and at the R&D Day, we will outline the company's anti-cancer strategy that will focus on these three key areas. Number one, reversal of resistance to IO therapy. Number two, reversal of cold tumors, which currently are not candidate for IO treatment, into hot tumors, which we expect will become candidate for IO therapy. Number three, prevention of immune-related adverse events, which can occur in approximately 40% of patients, and grade III/IV of these events can lead to permanent discontinuation of these IO agents.
We will share more about this at R&D Day. I would like to encourage you to attend that event. With that, I will now turn the call over to Rich, who will discuss our commercial and partnership strategy. Rich.
Thank you, Ramon. Our pre-launch activities and preparations for our commercial launch into the CIN market are building, with our PDUFA date clearly set for November. Over the next several months, our seasoned commercial leadership team is preparing to deliver a fully integrated market preparation and launch program to support a successful launch of plinabulin in early 2022, complete with elements such as driving awareness of the unmet medical need or what we call the neutropenia vulnerability gap. Continuing our large account outreach, preparing for NCCN guideline submission, KOL development, speaker mobilization, key stakeholder outreach, including patient groups and federal, state, and local legislative initiatives, medical symposia and education, publications, targeted advisory boards, and finalizing our patient support services to ensure broad access at launch. Specifically, we plan for a dedicated and focused team for the U.S. market.
Importantly, we will have a field reimbursement liaison team supported by a patient services hub in place to ensure effective reimbursement from day one to provide support for both providers and patients. We believe this extensive commercial strategy will position us well to successfully launch plinabulin combination therapy to capture long-term commercial success. We look forward to updating you on our progress with our pre-launch activities over the coming months. In China, we are taking a parallel path, having dedicated and focused commercial team build-out and partnerships discussions with potential synergistic commercial partners. I'll now turn the call over to Elizabeth to provide the financial update. Elizabeth?
Thanks, Rich. I'll now briefly discuss our first quarter 2021 financial results. For greater detail 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. I will now highlight some of the key financial results. R&D expenses in the first quarter of 2021 were $11.3 million, compared to $13.7 million in the same period last year. The decrease of $2.4 million was primarily due to a decrease in clinical trial expenses and non-cash stock-based compensation, which was partially offset by an increase in manufacturing costs and costs related to the plinabulin regulatory filings. G&A expenses were $6.4 million in the first quarter of 2021, compared to $2.9 million for the same quarter of 2020.
The $3.5 million increase was primarily due to higher personnel costs and non-cash stock-based compensation, as well as pre-commercialization activities for plinabulin. Net loss in the first quarter of 2021 was $17.0 million, compared to $16.1 million for the same period last year. Our cash balance at the end of Q1 was $90.6 million, which we believe will be sufficient to support our ongoing clinical programs over the next year, including our immuno-oncology pipeline, and to prepare for the potential launch of plinabulin in CIN in early 2022. With that, I'll now turn the call back over to Lan to conclude. Lan?
Thank you, Elizabeth. We have had an extremely productive period, and everyone inside the company feels the momentum as our vision of commercializing plinabulin and expanding our indications comes closer. From treating chemotherapy side effects to treating cancer directly, plinabulin is truly a pipeline in a drug, with its encouraging data showing efficacy in many indications. Plinabulin could be a game changer in cancer treatment by combining with checkpoint inhibitors. We intend to capture this value for shareholders and continue advancing our programs through clinical testing and into potential commercialization as novel cancer treatment options in the months and years ahead. Finally, 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. This concludes our prepared remarks today.
I will now ask the operator to begin our Q&A session. Operator?
Thank you. At this time, we'll be conducting a question and answer session. Our first question comes from the line of Jason Gerberry with Bank of America. Please proceed with your question.
Hey, guys. Good morning. Thanks for taking my questions. Two for me. Just your confidence level that plinabulin won't have an FDA Advisory Committee. I know that so far they have not asked or requested that an AdCom be scheduled, but given that it is a new mechanism of action, which is a typical trigger for convening a panel, curious if you can share your thoughts on maybe why an AdCom wouldn't be necessary in this particular instance. My second question is just as you look at the data generated with the triple plinabulin plus IO in tumors that have progressed beyond PD-1 therapy in the small cell lung context, what are your thoughts about looking at this combination in non-small cell lung?
Obviously, a bigger market opportunity, and I assume you're going to want to wait till you see the Dublin results before making any investment decisions. Just very curious your outlook there for the utility in non-small cell lung cancer. Thanks.
Yes. Thanks, Jason. This is Lan. Let me answer the first question regarding what our confidence regarding the AdCom. Second question, I think the triple IO to be extrapolated or later to have studies potentially in non-small cell lung cancer. I will give this time to Ramon to answer as he is the clinical brain behind all the study designs. For the no AdCom meeting, we did have in this a letter from FDA saying very specifically, there's no AdCom plan at this moment. We think that probably that's due to two very positive elements during the two-month review. Number one is FDA inspection did happen in our New York office in the beginning of May, and we do not have any 483 after the inspection. Secondly is we also had a large AOM meeting with FDA.
AOM meeting is the orientation meeting for NDA applications from FDA side. They usually are given to agents which had breakthrough designation and also have orphan disease and which are truly helping with unmet needs. That meeting had huge support from FDA side. They have almost 40 clinical leaders in CMC and clinical, all of those experts coming to the call, and we had a pretty nice meeting there. Potentially they were happy with what they hear. Another thing I think will add to the confidence, potentially no AdCom is, as you see from our earlier press release, we did show that ANC-based endpoints, such as prevention of peripheral neutropenia, is correlated to the reduction of clinical outcome, such as the incidence and duration and severity of severe neutropenia and also hospitalization.
That is a key element which we think gives FDA and also later for the clinical community confidence that the combination of plinabulin adding to that is providing meaningful and very clinical meaningful benefit for patients compared to the standard care, pegfilgrastim alone in preventing CIN, which does lift the standard care for the first time in the last 30 years. Does this answer your question?
Yeah, no, definitely. Thank you so much for the thoughtful answer.
Thank you. I'm going to give the second question to Ramon.
Yes. Thank you, Lan. Certainly, the goal is indeed to gather now with plinabulin, what you call proof of concept evidence, that it works in specific IO combinations. The next step will be that we move these combinations into first line. Moving into non-small cell lung cancer is certainly the plan as one of the next steps. There are two big IO combination strategies currently employed. We have the Merck approach with PD-1 inhibitor, combining that with chemo, and that also is a proof, of course, for first-line non-small cell lung cancer. We see an excellent opportunity for plinabulin to be added to that regimen to therefore get better survival benefit. Those are important points we are making. Plinabulin not only adds to the overall survival benefit, but also prevents important side effects.
With chemo, of course, that is neutropenia, and with IO agent, that is immune-related events. Plinabulin, therefore, is very uniquely positioned to not only increase overall survival but also prevent both neutropenia and immune-related events. The other big IO triple strategy that's being employed is by BMS, where they combine two different IO agents, PD-1 inhibitor, nivolumab with ipi. There is no chemo in the mix. However, there are much more immune-related AEs. There, again, plinabulin is very well positioned to both increase the overall survival but also to reduce the immune-related AEs. We start here with small cell lung cancer, yes. The next step will be we will move into first line, the non-small cell and other cancer types, and adding plinabulin to these different triple combos that are currently employed by the various big pharmas. Thank you.
Got it. Great. Yeah, look forward to R&D Day next week to maybe see, again, a little bit more of a query around the pathway. Would that be next steps in sort of the clinical pathway would be helpful to learn more about? Thanks.
Thank you, Jason, for your support.
Thank you. Our next question comes from the line of Maury Raycroft with Jefferies. Please proceed with your question.
Hi, good morning, everyone. Congrats on the progress, and thanks for taking my questions. First question is just for phase III DUBLIN-3. If you can provide any specifics on where you're at in respect to reaching the 439 events needed for the final analysis, and you've guided to top-line data mid-year, but do you think this will be more of an August or September update?
This is Lan. I can answer this great question. As of now, we did reach at least 439 death events, which is the final analysis criteria. We're still cleaning the data. No analysis has been done yet. I think we guided market that it's mid-year because when you do the cleaning to make sure the raw data is the same in the EDC system, that is an extensive process, and also there's additional sensitive analysis. We're still guiding it mid-year.
Got it. Okay. Also Go. Sorry, go ahead.
No, it's okay. Thank you.
Okay. The other question was also related to phase III DUBLIN-3. Just wondering if there's anything additional you can say on the patient baseline characteristics at this point, including proportion of patients who are PD-1 failure patients, and how baseline characteristics factor into your efficacy expectations. Is this something we can learn more about at your R&D Day event next week?
First, I think our R&D next week will be very comprehensive. We are going to go into details into the designs, and also primary and secondary endpoint for the DUBLIN-3 phase III study. I think that's the right platform to review the details. Secondly, for the baseline characteristics, they're all balanced. We are selecting the measurable non-Asian patients, which is the mechanism-enriched population pre-specifically. Secondly, this is in the EGFR wild type, which is 85% of the non-small cell lung cancer. This is much larger than the EGFR mutant or the ROS or ALK mutation population. This is the very sick patients, as you know, that pazopanib, the TKI, actually does not even work as well as docetaxel in this EGFR wild type patient population. We do stratify patients who had previous PD-1 or PD-L1 experience, so those arms balance.
We have a limited percentage in those patients in this study.
Okay, that's helpful. Likewise, looking forward to the R&D Day event next week. Thanks for taking my questions.
Thank you for your insightful question.
Thank you. Ladies and gentlemen, as a reminder, if you'd like to join the question queue, please press star one on your telephone keypad at this time. Our next question comes from the line of Andy Hsieh with William Blair. Please proceed with your question.
Great. Thanks for taking my questions. Congratulations on all the regulatory milestones that you've achieved in the past six to nine months. My question has to do with kind of the regulatory sentiment. The basis of the question has to do with, during the COVID pandemic, I think NCCN was really aggressive in terms of updating guidelines regarding management of CIN patients. I'm just wondering, through the breakthrough designation discussions with the FDA priority review, did the agency bring up kind of that factor or that benefit that plinabulin can provide? Especially, maybe in the U.S., we're probably 60% over, but I guess on a global level, we're still very much in the pandemic.
Yeah, thanks for this great question. Let me probably start the first half the answer, then I'm going to give the baton to Rich, who actually also has done a lot of market research to see how this NCCN guideline update is going to affect the market reach for the plinabulin and G-CSF combination. First is, I think FDA is kind of independent from the NCCN guideline members. As you see, we did get breakthrough. This is for the unmet medical needs and also to raise the standard of care. That's the two criteria for the breakthrough. Secondly, we're also very grateful for FDA to give us priority review. That's another help, or in a way, supported from FDA saying that this is a truly unmet medical need.
We like to have this expedited review time so that if the drug is proven to be effective, want to get to the market as soon as possible. Right. That's the backdrop. Probably I can give the baton to Rich to talk about how this NCCN guideline update is affecting how the doctors using G-CSF and later our market penetration potential.
Great. Thanks, Lan. Thanks, Andy, for the question. With the NCCN guideline change last March, we've seen the physicians actually begin to go deeper into the intermediate risk category. Ongoing discussions with the KOL community, many of whom are deeply engaged with NCCN, indicate that they do not believe that the NCCN will revert back to the old guidelines, which is high risk only, anytime soon. They believe that this is ongoing. Mostly a couple of factors. One, there's a belief that patients or people, the community in general, will need boosters in the long run. Number two, cancer patients are among the most immunocompromised patients we have. Obviously, we intentionally immunocompromise them with chemotherapy, and so they need added protection in this kind of an environment.
The updated guidelines appear to be with us for quite some time, and the physicians are getting quite comfortable with it, as are the payers. We see that obviously the addressable market has grown by more than 100% because of these updated guidelines. The high-risk patients represent 35% of the patient population, and intermediate risk represents 37%. We think this bodes well for the opportunity because plinabulin is the only drug that can actually raise the standard of care in CIN. We're pretty excited about the opportunity to help out and improve the standard of care. We believe this is a great opportunity for us, for the providers, and for the patients as well. Thanks.
Oh, great. Maybe just to follow up, Rich, and also Elizabeth. From a modeling standpoint, how do you think about the ramp? Rich, in your prepared remarks, you did talk about you're building an integrated infrastructure here in the U.S. How should we think about that SG&A build, maybe basically from now to PDUFA and maybe from PDUFA to launch?
Yes, great question. We have a threefold pre-launch approach, and we've talked about this before. We're talking about addressing this and driving awareness of this neutropenia vulnerability gap, day one to day seven, eight, nine. This is where plinabulin has its effect and is the perfect partner for G-CSF. With 1.4 million units of G-CSF being used and this base is growing over time because of, obviously, this NCCN situation and the opportunity to improve the standard of care. Addressing this neutropenia vulnerability gap and being the perfect partner for G-CSF, I think is a really good opportunity. Positioning the plinabulin with the key decision makers in payers, in large accounts, anyone affected by contracting, we can actually talk to now. We are out talking to them right now, making them aware of the potential that the drug does in fact have.
Activating these key accounts, making sure that they know who BeyondSpring is, they know that the drug is in fact coming, and then being prepared for broad access, availability, and access for patients. Making sure that our systems are up and running. As we think about the infrastructure build, we're well on our way. We're really confident we have the ability because, as Lan mentioned, a deeply seasoned commercial team that has done this many times before. When we think about our SG&A ramp, we will be identifying our sales team and only hiring them after we have a guaranteed approval. Because it's difficult to launch a product during the holiday season, that's why we refer to launching this in the first quarter. We don't want to have the physicians distracted by the holiday.
It's not good for the product, it's not good for the company, it's really not good for patient care. We want to make sure that we bring the product to market when we can attract the attention of the physician and get their full attention, and that's generally after the holidays. That's what we'll be doing. With that, I'll turn it over to Elizabeth for any additional comments.
Yes, thank you. I just want to continue to assure everyone that we're making all of the plans to make sure that the company is well funded during this time period of pre-launch, as well as preparing for the launch. You'll note in our statements that we've just filed that we are sufficiently funded for the next year. However, that said, we are always evaluating options for getting other funding into the company, and our preference at this point is some form of non-dilutive financing to just boost the balance sheet as well as, at the right time, to consider partnerships.
Okay. Thank you very much for answering all my questions.
Thank you, Andy, for your continued support.
Thank you. Ladies and gentlemen, this concludes our question and answer session. I'll turn the floor back to Dr. Huang for any final comments.
Thank you again to everyone for joining us for the call today. We're very proud of our accomplishments and look forward to speaking with you again on our R&D day on June the 26th, next Friday. Thank you.
Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.