BeyondSpring Inc.
Q2 2021 Earnings Call Transcript

Published: 10 Sep 2021

[Operator:]

Good morning. Welcome to BeyondSpring's Second Quarter 2021 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. As a reminder, this call is being recorded today, September 10, 2021. I will now turn the call over to Monique Kosse of LifeSci Advisors.

[Monique Kosse:]

Thank you, everyone, for joining today's call. I would like to advise listeners that comments made on today's call may reflect forward-looking statements that are related to such matters as BeyondSpring's clinical and preclinical research & development activities and results, regulatory and commercial plans, industry trends, market potential, collaborative initiatives and financial projections, among others. While management believes that its assumptions, expectations and projections are reasonable in view of the currently available information, you are cautioned not to place undue reliance on these forward-looking statements. The company's actual results may differ materially from those discussed during this call for a variety of reasons, including those described in the forward-looking statements and Risk Factors sections of the company's 20-F and other filings with the SEC, which are available on the Investors section of BeyondSpring's website. Joining us on today's call is Dr. Lan Huang, BeyondSpring Co-Founder, Chairman and Chief Executive Officer; Dr. Ramon Mohanlal, Executive Vice President, Research and Development and Chief Medical Officer; Richard Daly, Chief Operating Officer; and Elizabeth Czerepak, Chief Financial Officer. It is now my pleasure to turn the call over to Dr. Lan Huang. Lan?

[Lan Huang:]

Hello, everyone, and thank you for joining today's call. We are very pleased to be here today reporting our second quarter results and providing an update on the many meaningful events in the recent weeks. Everyone here at company is very excited as we have accomplished so much, but most importantly, we're most excited for patients who are our North Star, who can be helped by our lead asset, plinabulin. Plinabulin is a first-in-class selective immunomodulating microtubule-binding agent or SIMBA. With clinical evidence from DUBLIN-3 and our CIN studies, we have revealed the dual benefit of plinabulin in a direct anticancer benefit of significantly extending overall survival while also significantly reducing severe neutropenia induced by chemotherapy, which would be beneficial to patients in need. From the execution point, we have much more to look forward to in the next 6 to 12 months, including

[Ramon Mohanlal:]

Thank you, Lan. As Lan indicated, we are eagerly awaiting the PDUFA date for the CIN application later this year. We were naturally awaiting the results from DUBLIN-3 to obtain confirmation of plinabulin's anticancer activity, which we have now. It was exciting to see that the plinabulin docetaxel combination in DUBLIN-3 has met both the primary endpoint for overall survival and the key secondary endpoints for ORR and PFS. The significant reduction in Grade 4 neutropenia by fivefold with the combination versus docetaxel alone supports plinabulin's CIN prevention benefit. The full year OS rate at 10.6% for the combination with plinabulin versus 0% with docetaxel alone underscores the durable anticancer benefit for plinabulin and is consistent with its immune mechanism of action. I also would like to mention that we conducted DUBLIN-3 at high quality standards on the U.S. GCP. We used quality CROs for the conduct of DUBLIN-3. ICON was our global CRO for site selection, patient enrollment and monitoring. All blood samples were sent to Covance Central Laboratory for pharmacokinetic and hematology assessments, including neutrophil count. ICON Pharmacovigilance was used for safety processing. As Lan mentioned, plinabulin's next focus in our clinical development program is to develop IO combinations in multiple cancer indications. Earlier this year, we presented Phase 1 clinical data with plinabulin in combination with nivolumab and ipilimumab in small cell lung cancer, demonstrating a doubling of the anticancer results normally seen with nivolumab and ipilimumab alone. In that study, we also demonstrated that plinabulin could reverse resistance to prior checkpoint inhibition therapy. Specifically, in this small cell lung cancer Phase 1 data, which was presented at ASCO earlier this year, patients from U.S. sites had an ORR of 46% in second and third line, and an ORR of 43% for PD-L1 inhibitor failed patients, which also had a long duration of response, as long as 18 months. And at MD Anderson, we are conducting an investigator-initiated trial in 7 different cancers, evaluating the safety and tolerability of plinabulin in triple IO combination therapy with both PD-1/PD-L1 antibodies and radiotherapy in PD-1/PD-L1 failed patients. The first patient was enrolled in this Phase 1b/2 trial in June of this year. As was mentioned before, resistance to immunotherapy is fair unmet medical need and we believe plinabulin may have a potential of synergistic anticancer effect when combined with checkpoint inhibitors and radiotherapy. Based on plinabulin's unique mechanism of action and early clinical data, we believe that adding plinabulin to checkpoint inhibitor therapy with or without chemotherapy has the potential to improve anticancer efficacy while reducing toxicity with IO and/or chemotherapy. We believe that these early trials are providing collective evidence of plinabulin's role in addressing the unmet medical need in immuno-oncology therapy. On the organizational side, we are rapidly building our medical affairs capabilities in support of the upcoming commercial launch efforts. With that, I will now turn the call over to Rich, who will discuss our commercial preparations. Rich?

[Richard Daly:]

Thank you, Ramon. Our prelaunch activities and preparations for a commercial launch in the CIN market are building with our PDUFA date set for November 30. 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; educational symposium; 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 1 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 prelaunch activities in the coming months. And now, I'll turn it over to Elizabeth to take you through the financial results. Elizabeth?

[Elizabeth Czerepak:]

Thanks, Rich. I will now briefly discuss our second quarter 2021 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, I will now highlight some of the key financial results. R&D expenses in the second quarter of 2021 were $11.3 million compared to $11.0 million in the same quarter last year. The increase of $0.3 million was primarily due to an increase in personnel costs and noncash stock-based compensation expense, partially offset by lower clinical trial expense. G&A expenses were $9.0 million in the second quarter of 2021 compared to $2.6 million for the same quarter of 2020. The $6.4 million increase was primarily due to higher personnel costs, noncash stock-based compensation expense, and higher costs associated with pre-commercialization activities for plinabulin. Net loss in the second quarter of 2021 was $19.3 million compared to $12.8 million for the same period last year. Our cash balance at the end of second quarter was $51.3 million, and we had short-term investments of $25.0 million, which we believe will be sufficient to support our ongoing clinical programs over the next year, including our immune-oncology pipeline and to prepare for the potential launch of plinabulin in CIN in early 2022. In addition to reported available cash, we will also receive from Hengrui approximately $45 million for a $30 million upfront payment, plus an equity investment into the China subsidiary related to the plinabulin partnership in China, which Lan described. I do also want to mention that in the U.S., Rich has updated on our efforts to prepare for our own launch of plinabulin in CIN, and we are also evaluating potential partnership opportunities in the U.S., Europe and other parts of Asia outside of Greater China. We are only considering the very top companies who could bring great synergies and help us optimize the value of plinabulin globally. With that, I will now turn the call back over to Lan for closing remarks. Lan?

[Lan Huang:]

Thank you, Elizabeth. We are very proud of our accomplishments thus far. We have had extremely busy and productive period recently, but we're just starting. Everyone feels the momentum building and our excitement grows as our vision of commercialization plinabulin and expanding our indications come closer with the potential to help many patients in need. We invite everyone to watch for us at ESMO on September 20, where we will make a late-breaking presentation on our DUBLIN-3 Phase 3 data in non-small cell lung cancer, 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 operator to begin our Q&A session. Operator?

[Operator:]

. Our first question is coming from the line of Josh Schimmer with Evercore ISI.

[Josh Schimmer:]

First, what type of information should we be booking for from the DUBLIN-3 trial at ESMO? And specifically, are we going to be getting the subset analysis which investors have been very focused on? And then second, investors are clearly concerned that the DUBLIN-3 trial may not suffice for FDA approval, given that the trial was run mostly outside the U.S. and in PD-1 naive patients. As you are discussing the program with partners, do you expect that you are going to need to wait for full approval by the FDA to capture the full value of the program in some kind of a partnership deal?

[Lan Huang:]

Thank you so much Josh for your continuous support and thanks for this great question. So allow me just to touch on both those questions. Number one is, with the ESMO presentation, we are going to show the whole data the ITT population with all of the specific numbers with it and in addition we're also going to show the subset analysis. Everyone is so eagerly waiting to see including the PD-1/PD-L exposed patients and also the Western patient subset. So that's number one question. Number two is regarding your question on the relevance of the study with limited patients from U.S., how it relates to the U.S. population, right? So we think that currently our patient popularly does capture the current landscape of treatment to the biggest spend because we do have patients who have exposed to PD-1/PD-L1. And from the previous experience in FDA approvals for oncology drugs, there were incidents of approval using limited patient data from the U.S. According to the IQVIA report, 27% of the U.S. FDA oncology drug approval actually use less than 10% data from the U.S. So of course, this is a review issue. So we will be eagerly discussing this with FDA in our planned pre-NDA meeting. We are planning for quarter 4 of this year. Regarding the partnership discussion, I think this, of course, is a very important topic to discuss, but we cannot give any details at this moment.

[Operator:]

The next question is from the line of Jason Gerberry with Bank of America.

[Jason Gerberry:]

Two for me on DUBLIN, probably not a big surprise. But just can you, Lan, maybe walk us through the history of the trial, the interim analysis and whether median OS or Kaplan-Meier OS were the prespecified primary endpoint and whether there were any protocol changes that occurred during the trial? And then my second question is just -- there isn't much debate that Kaplan-Meier OS is a gold standard for measuring OS. But I think investors believe that support of median OS is needed to ensure that the clinical benefit is meaningful. So just love to get your thoughts on the regulatory implications of support of median OS, particularly if it falls in a more gray area or even a negative P-value.

[Lan Huang:]

Yes. Well, thank you so much, Jason, for your great question regarding the more details in the history of DUBLIN-3 and also the primary endpoint questions. So first is, DUBLIN-3 has been ongoing for almost 6 years. So it has been a long trial because it is 559 patient enrollment globally in U.S., China and Australia. So along the way, the treatment landscape has also changed, right? And there are PD-1/PD-L1 treatment approved during the study. So we did -- during the study, we did update the protocol to include the allowed lines to have PD-1/PD-L1 failed patients in the study and stratify them. So that's why we are confident with the balancing of 2 arms with PD-1/PD-L1 exposed patients. And then secondly, regarding the primary endpoint. So the primary endpoint has always been overall survival, it has never been changed. It's just analysis of the data, methods, right? So one is, using the log rank P-value looking at the whole Kaplan-Meier OS curve. But including, in there, there will be median OS shown. And in addition, we're also putting the restricted mean survival time, which is looking at the mean OS because plinabulin is an immune agent. But mean potentially captures more of the OS benefit for plinabulin arm, but both are going to be shown in the ESMO and also with the NDA filing. So everything is transparent, and everybody can see what is the profile for plinabulin. So in the end, the drug is profiled from the KM OS graph, and that's the key. So along the way, we did have 2 interim analysis, right? So there is a little P-value hyp, there’s little hyp for the final p-value, which we need to meet for the log-rank P-value, which is 0.04 fixed. And what we have said in top line is log-rank P-value for DUBLIN-3 in the plinabulin plus docetaxel versus docetaxel arm is less than 0.04. So that is -- it does need this statistic in extending overall survival in the primary endpoint. So of course, everybody will see more details in the ESMO.

[Operator:]

Our next question is from the line of Maury Raycroft with Jefferies.

[Maurice Raycroft:]

To tie the subset analysis together for PK bridging data between Western and China patients, is it possible you could disclose some of the PK bridging data at ESMO or at some other point prior to filing the NDA?

[Lan Huang:]

Yes. Thanks for this great question because this is very important for us to be able to combine the Western and Asian patient data for the NDA submission, not only for U.S. but also for China FDA. So we had done extensive population PK and everybody in our CIN studies and also in lung cancer study, everybody has a population PK. So we have rich data for almost -- over like several hundred patients on those data. So currently, we have submitted those data to the regulatory agency and this is not -- the PK comparison data usually is not in the presentation or for the registration study or in the publications. Of course, if everyone is very interested, probably in the future we should have some kind of public review on this later, but this is not -- it's not going to be discussed in the ESMO, but it is consistent, and we're very confident with.

[Maurice Raycroft:]

Got it. So you're confident in the consistency that you're seeing between the patient population?

[Lan Huang:]

Yes, yes. Yes, they are comparable, they similar in the population PK in Asian versus Western patients. We have shown that in many studies. And all the PK data came from Covance, right? We use Covance as our central lab.

[Maurice Raycroft:]

Okay. And then one other question just for the CIN NDA that's under Priority Review. Can you talk more about the regulatory interactions and feedback and whether you've had a mid-cycle review communications and any label discussions yet?

[Lan Huang:]

Yes. Thanks for this great question. Everyone is eagerly waiting for the final date, which is November 30. Yes. So as the FDA has been communicating with us in frequent manner and very supportive of our submission because we did have AOM meeting before the document has been successfully received by FDA. We also had a mid-cycle review. And we haven't got to the label discussion yet because it usually is 1 to 2 months before the PDUFA date, then there will be a label discussion.

[Operator:]

Next question is coming from the line of Andy Hsieh with William Blair.

[Andy Hsieh:]

So I have 2 questions really kind of related to Jason's questions before. One is, is really, Lan, maybe you can comment on just how DUBLIN is conducted from a quality control standpoint, data integrity standpoint? I think there's a lot of questions regarding that. And also since, Lan, you talked a little bit about the P-values, I wanted to kind of get your clarification in terms of the P-values listed in the presentation back several weeks ago following the DUBLIN-3 top line results. I noticed that there were a lot of the P-values that basically provided a range and not basically like a single number. I just want to clarify that, that is due to the fact that analysis was still ongoing, and that was kind of like the topline results, and we'll basically get detailed exact P-values at the ESMO conference.

[Lan Huang:]

Yes. Thank you so much, Andy, for your great questions and also always your great support. So let me answer your 3 questions in sequence. So number one is, we are very confident with our quality of the data because we are using the quality CROs to conduct the study as what Ramon just related to you. So our global CRO is ICON, which in charge of entire selection and patient enrollment and also the monitoring. And secondly, we are also using Covance Central Labs to look at all of our blood samples to evaluate the PK and also blood chemistry, including the A&C numbers, because you know that A&C actually is important for our secondary endpoint, looking into the Grade-4 neutropenia reduction in plinabulin versus the docetaxel arm. And thirdly, we also used ICON PV to actually do the SAE reporting and also collect all the AE data for all the studies, including DUBLIN-3 and also CIN studies and all the ITT studies. And the last but not least, I also want to mention we also used CRT, which is a central lab company, and they actually sent all the ECG machine to all the sites to look at -- to take triplets for the ECG to look at cardio safety for the drug. So all of this is well validated CROs and also our conduct is under U.S. GCP. So that answers your first question. And number 2 is the data integrity. So actually, we do use independent statistical company to do the analysis of the data. And so -- and also it's also a single-blinded study to the patients, right? So when you look at the quality of live data, it will be very trustworthy because patients do not know which arm they are on. So that's the second question. The third question is a great question, a clarification for the P-value in all the -- some of the primary and also the secondary endpoint which we actually had released in the topline because this is a topline, right? So -- and really, we cannot disclose much because we are saving it for a big major medical conference which is coming up in ESMO. So that's why it was just only showing a range.

[Andy Hsieh:]

Okay. Great. Thanks for all the detailed explanations, Lan. Maybe just one more, kind of heading into the ESMO conference, I wanted to get your perspective on how you would view the PFS data. Obviously, whenever you look at OS, it's always kind of confounded by subsequent therapies. So maybe kind of a 2-parter. One is, maybe can you comment on based on the geography, what are some of the subsequent therapies that patients could get on DUBLIN-3? And also, how would you kind of interpret and look at the PFS results in the context of the positive OS?

[Lan Huang:]

Yes, that's really a brilliant question because for all the clinical studies, I think the gold standard is OS, right? Because in the end, we want to provide long-term survival for patients and that is what all the patients and the FDA and also physicians are looking for. So OS is the gold standard. But in the end, in addition, we also want to use PFS and ORR also to look at the drug effect, right? And there's no noise from the later treatment. So that is what you are getting at. So do we see a drug effect adding to the benefit of docetaxel in the PFS? And as you see, the P-value is less than 0.01, right, from the directional P-value, which we shared in the topline. So we are seeing better improvement in plinabulin adding to docetaxel, not only in the PFS benefit, right, but also in the ORR, which also showed statistical significance. And your last question also asked about what's the later treatment after the patient is out of the study? As you know, both -- it is a randomized study, so both arms are balanced and patients, after they get out, of course, they will do have a desire to live, so have a good therapy to be treated. So afterwards, they usually use TKIs and also they do have PD-1 or PD-L1 exposures, but limited, and also they are balanced.

[Operator:]

The next question is coming from the line of Joel Beatty with Baird.

[Joel Beatty:]

For the CIN indication, there's been recent attention among investors that most of the patients in the trials were from outside the U.S. Could you discuss if FDA is okay with the number of U.S. patients in the CIN studies? And then also, could you discuss how closely the chemotherapy regimens used in those CIN studies resemble what's currently used in the U.S.?

[Lan Huang:]

Well, thank you so much, Joel, and thanks for initiating the report for us recently. Yes. So this is a great question. So for the CIN indication, as you know, we are going after a broad label for plinabulin combined with G-CSF in preventing CIN in -- for chemotherapy and all solid tumor, right? So it is a broad label and Study 106 Phase 3 or PROTECTIVE-2 is a pivotal study, which supports this label. In addition we'll also have 5 other clinical studies to support this label, right, from a safety point of view and also from plinabulin's pharmacology in its working in protecting neutrophil in week 1 after chemotherapy as what Rich... …96% to 100% according to literature, right? So there's a lot of room to improve there. And so -- but then -- so in a way, it's not so relevant to show if TAC is still used in the U.S., it's more like it's using as a template to evaluate the drug effect for plinabulin in combination with G-CSF or any new current -- any new agent in development for the CIN prevention. So coming back to the 106 Phase 3 patient population, it is mainly coming from the 2 countries, right, around 50% in China, 50% around in Ukraine. So Ukraine patients are representing the Western patients and they’ve agreed with that, China versus Asian patients because U.S. is just really use TAC because TAC with G-CSF still have such harsh integration for neutropenia as high as 100%, but it's not really used that very much, a lot of targeted therapies are used for breast cancer. And then for the Western -- for the Eastern Europe and China still TAC is used, that's why you can't enroll patients to really evaluate plinabulin drug effect. And so far FDA hasn't had any issues with this breakdown because they have seen our raw data. They also look at our clinical conduct and also look at the eTMF and everything, and then this has not been an issue, and they have successfully accepted our filing with Priority Review and also with no ODAC.

[Joel Beatty:]

Maybe one more question related to discussions with potential partners for the U.S. and other countries. How much of the focus on those potential partners is on marketing versus on clinical development of additional indications?

[Lan Huang:]

Well, so I think this is probably -- it's still ongoing with the potential partners for the U.S. global market, potential partnerships. And this is -- of course, it's a combination of all of that, right? Because it is -- very importantly, plinabulin is strong as potentially now has this dual benefit in anticancer benefiting extending survival and also in reduction of chemotherapy in neutropenia. So with that profile is really is a gateway into multiple indications, we believe in the IO combination therapy. So of course, partner will be very interested in those additional development, which will give a lot of potential for plinabulin and in the end is to help many patients. Of course, commercialization is near term, right? So that's also in the discussion point. But as you see from our recent partnership deal with Hengrui, which is a very, very respected company in China in the oncology space, and we do think the synergy is also giving us 1 plus 1 with the 2 in their discussion, as you see from the terms, right? So commercialization, we are very much grateful to their support because they have top sellers of PD-1 and also top sellers of docetaxel and top 3 seller of PEG-filgrastim, but also, they have a lot of other agents in their pipeline, actually, which could potentially also in combination with plinabulin, because plinabulin is a very interesting and multitalented child in our way. So those are going to have more indications and more differentiated therapy regime potentially for patients in need.

[Operator:]

. The next question is from the line of Joe Pantginis with H.C. Wainwright.

[Joseph Pantginis:]

Thank you for all the details. And I think you've done a good job really in addressing a lot of potential concerns that are out there. So thanks for that. So I actually have a couple of logistical questions. First, with regard to Hengrui. Just wanted to see what are some of the rate-limiting steps right now? I mean you have some tech transfer to do. What other things are outstanding to make sure that they could efficiently launch plinabulin efficiently?

[Lan Huang:]

Yes, that's a great question. And that's what we are currently actively doing with Hengrui. Our China team is working with them starting from the second day from the signing. So from August 26 we have been working daily with our partner at Hengrui, and they are very eager to get all of the medical science, as on team, on Board, understanding and also making the messaging right.

[Joel Beatty:]

…is just regarding like the milestone payments, how are you looking to account for these and amortize or recognize upfront or what have you?

[Elizabeth Czerepak:]

Yes. Thank you for that question, Joel. And we are very actively discussing that with EY, who's our global auditor. And we, for sure, will be booking all of the monies that come in. We've not given up booking of revenue. And yes, we'll have to go through the dance with them on deciding how to book the revenue.

[Joel Beatty:]

Understood. And thanks for all the details, looking forward to ESMO. Sorry, please go ahead.

[Elizabeth Czerepak:]

Yes. And I was going to say, and as far as the milestones go, of course, those will receive, I'm sure, very normal accounting treatments, and hopefully, some will be problems of booking that we'll have to deal with sooner rather than later. We expect that.

[Operator:]

There are no further questions. And I will now turn the call over to Dr. Huang for her closing remarks.

[Lan Huang:]

Thank you, operator. Thank you again, everyone, for joining us for the call today. Your time is precious. And thank you for being on this meaningful journey with us to support us and together, our partners who help many patients in need. Thank you, and have a nice day and have a nice weekend.

[Operator:]

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.