Spectrum Pharmaceuticals, Inc.

Thank you, operator, and good afternoon to everyone. Thank you for joining us today for Spectrum Pharmaceuticals third quarter 2020 financial results conference call.

Our third quarter financial results press release was sent out earlier this afternoon and is available on our website at www.sppirx.com. Joining me on the call today from Spectrum Pharmaceuticals will be Joe Turgeon, President and CEO; and Dr.

François Lebel, Chief Medical Officer. Before we get started, I would like to reference the notice regarding forward-looking statements included in today's press release.

This notice emphasizes the major uncertainties and risks inherent in the forward-looking statements that we will make this afternoon. These statements are not guarantees of future performance and undue reliance should not be placed on them.

Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such forward-looking statements. With that, let me turn the call over to Joe Turgeon, CEO of Spectrum.

Thank you, Kurt. Good afternoon everyone and thank you for joining us today on the call.

As always I really appreciate your interest in spectrum. I'm pleased with the progress that Spectrum has continued to achieve over the course of this entire year.

And that's despite the challenges to the pandemic and the impact it's had across our industry. While Spectrum isn't immune to the impact of the pandemic, our staff has demonstrated dedication, resilience, and focus to position the company for a strong finish in 2020.

We have a number of key milestones coming up in the next couple of months. We'll be meeting with the FDA to review a filing strategy based on the positive results we announced earlier in the quarter for poziotinib.

These data demonstrated that poziotinib met the pre-specified primary endpoint in patients with non-small cell lung cancer HER2 exon-20 insertion mutations. This is a positive outcome and is significant for Spectrum and for the patients with this devastating disease.

We’ll also be providing an update on the overall poziotinib program, including dosing strategy and top line results from Cohort 3 prior to the end of the year. Last week, we announced that the FDA was deferring action on the BLA for ROLONTIS.

The reason for the deferral was the agency's inability to inspect the Hanmi Bioplant in South Korea due to travel restrictions related to the COVID-19 pandemic. The FDA confirmed that this was not a complete response letter, otherwise known as a CRL.

This means that our file remains active. We have answered all the inquiries from the FDA, and we're not aware of any outstanding items other than the inspection.

We will be prudent with our financial resources and have gated certain activities pending further feedback or action from the FDA. Regarding the ROLONTIS plant inspection, our partner Hanmi Pharmaceuticals is a well-established global biopharmaceutical player with a world-class manufacturing facility.

Hanmi is the second largest pharmaceutical company in Korea, behind only Samsung. They're prepared for the inspection and willing to be accommodative to the needs of the FDA as it strives to meet the regulatory obligations.

They've been a great partner and are working in tandem which Spectrum to obtain an approval for ROLONTIS as soon as it is possible. I'm real confident in our ability to meet our corporate objectives in advance of programs with the aspiration of bringing new treatments to the patients with cancer, who needed it.

With that, I'm going to turn over the call now to Dr. François Lebel, CMO for an update on our clinical development progress.

Dr. François?

Good afternoon, everyone. It's good to be with you today for a short update.

We have discussed previously the positive outcome for Cohort 2 of the ZENITH20 clinical trial. We remain very excited by these results and look forward to our pre-NDA discussion with the FDA in the near-term.

Let me remind you that there is no approved treatment for patients with HER2 exon-20 insertion mutation in non-small cell lung cancer, and we believe pozi has the potential to fill an important therapeutic gap in an area of great medical need. Patients enrolled in the ZENITH20 Cohort 2 receive 16 milligram of poziotinib once daily.

Most patients were heavily pretreated, including chemotherapy and immunotherapy. The primary endpoint was objective response rate as defined by RECIST 1.1.

The intent to treat analysis demonstrated an ORR of 27.8%. The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17% with a 95% confidence interval.

At the data cut off, with a median follow up of 8.3 months, the responses were durable with a median of 5.1 months, and seven patients continued to receive drug after one year. Progression free survival was 5.5 months with a disease control rate of 70%.

The safety profile was in-line with the type of adverse events seen with others second generation tyrosine kinase inhibitors. We also presented the results for Cohort 2 at the European Society for Medical Oncology or ESMO at their Virtual Congress in September 2020.

This was the first presentation of the medical and – to the medical and scientific community of the positive result for this large registrational trial. We are preparing for the pre-NDA meeting with the FDA for pozi, which has already been scheduled.

We will discuss the path forward to registration seeking initially an indication for the treatment of patients with previously treated locally advanced or metastatic non-small cell lung cancer with HER2 exon-20 insertion mutation. Additional cohorts are still underway in this pivotal trial.

Results for both Cohort 1 and 2 have been reported, and Cohort 4 in the first-line HER2 exon-20 insertion mutation is now actively enrolling at 8 milligrams BID. We plan to update you further before the end of the year on our poziotinib dosing strategy and a fully enrolled Cohort 3 in first-line EGFR non-small cell lung cancer patients that received 16 milligrams in a single daily dose.

The exploratory Cohort 5 is enrolling well with over 110 patients to date and successfully provides us data to further define the minimal effect of dose. We have recently stopped enrollment in the 10-milligram per day dosing arm as during safety reviews it demonstrated and [enhanced] safety profile, but sub-optimal anti-tumor activity.

An indirect benefit of this early action is to accelerate the enrollment in our 6 milligram and 8 milligram BID dosing arms. We will be providing additional data in a future scientific meeting.

Now let me shift to ROLONTIS. Our BLA for ROLONTIS is supported by robust clinical data from two large randomized clinical trials.

ROLONTIS met the primary endpoint of non-inferiority in duration of severe neutropenia and met all the secondary endpoints. The safety profile was similar to pegfilgrastim.

I should mention here that we will be presenting a poster at the San Antonio Breast Cancer Virtual Meeting taking place this coming December 8 to 11. The poster will be available for viewing prior to the meeting, and shows the pool and analysis of two Phase 3 trials demonstrating the strength of our clinical package.

As a reminder, enrollment in our same day dosing study continues. This is an exploratory study that evaluates the dosing of ROLONTIS on the same day as chemotherapy.

We expect to have data by the end of the year that will determine whether we move to an expansion phase of this study. As to the deferred action, on our ROLONTIS filing, we have answered all questions from the FDA, related to the review of the BLA, and we've had advanced labeling discussion.

On the manufacturing side, we have conducted multiple mock inspections of our plant and are exploring ways to expedite the inspection, possibly using alternative methods to ensure the earliest completion of the review of our BLA during this COVID-19 pandemic. We look forward to updating you on important program milestone in the next two months, including the outcome of our poziotinib registration discussion with the FDA.

I will now turn it over to Kurt for some insight into our third quarter financials.

Thank you, François. Our SG&A expense for the third quarter of 2020 was 15.1 million versus 13.1 million in the previous year.

R&D expense was 24.5 million versus 17.2 million. The increase in R&D expense relates primarily to a purchase of $8 million of ROLONTIS drug substance in the third quarter, compared to no purchases in the third quarter last year as we kept the manufacturing facility in a state of readiness for an FDA inspection.

Recall that the accounting rules require us to expense this inventory as R&D expense until the product is approved, but when we sell this inventory, it will be at a zero cost of goods. Other income expense for the third quarter was a loss of 9.1 million, compared to income of 2 million in the period a year ago.

The loss is primarily related to a decline in the market value of our equity position in CASI. Our net loss for the quarter was 48.5 million versus 26 million in the comparable period in 2019.

On a non-GAAP basis, which primarily backs out stock compensation costs, and the change in value of our CASI securities, our loss for the quarter was 35.2 million versus 24.5 million in the prior year period. We ended the quarter with 198.3 million in cash plus marketable securities.

The cash balance reflects the proceeds from our financing in late July that raised a net 82 million. Operating cash burn, which is the best measure of our ongoing cash flow was 28 million for the third quarter.

This is consistent with where we've been the last few quarters. And as you can see, we are well positioned financially with plenty of runway to continue the development in commercialization of our late stage assets.

With that, let me now hand the call back over to Joe.

Thank you, Kurt and thank you Dr. François.

I think you can see from everyone's remarks the spectrum continues to make strong and steady progress on our pipeline. In the coming weeks, we'll be doing all that we can to facilitate the completion of the inspection of our ROLONTIS manufacturing facility.

We look forward to updating you later this year on our FDA discussions on the registrational pathway for pozi, and is sharing additional results for our ongoing cohorts in the ZENITH20 clinical trial. Let me remind you that we will be participating in several upcoming healthcare investor conferences and hope to connect with many of you at that time.

Once again, I'd like to thank our entire team for their hard work, their dedication in these unprecedented times. We look forward to keeping you informed on our future progress.

And with that, I'd like to open up the call for questions. Operator, if you could open up the call, please.

I'd appreciate it.

Hey, everyone. Hi, Joe.

Hey, Maury.

Hi. Thanks for taking my question.

So, first question is on ROLONTIS. So, François mentioned label discussions, just wondering if you can elaborate on that.

And then you mentioned the mock inspections, and I'm wondering if that's something FDA asked for and how that could help move the process along. And I guess is FDA considering potential to do a virtual inspection?

Yeah, François why don’t you take and I’ll jump in after. There is really three questions in there.

Let’s start with the label question you asked. François any comments there?

Right. Sure.

So, as we've indicated in my remark, and Joe's, the – look to our knowledge, right, we have received during the review of this file many questions, we believe that we've answered all of them. And that the FDA was satisfied.

But of course, we don't know that until, you know, they approved this drug. To our knowledge, the only thing outstanding right now, is the inspection of our manufacturing, a main manufacturing plant.

I think the second component was, would they consider a different alternative form of inspection? So, actually, I was just reading earlier today that the FDA has actually issued a statement yesterday, that they're in the process of developing guidance for interactive video, GMP evaluation.

So that's one thing that we certainly would be open to. We have not specifically talked to them about that yet.

And as you may know, the European agencies are conducting plant inspection using technology like that. FDA had issued guidance for priority drugs that they were considering that, but now, the news of yesterday is that they are in the process of developing guidance for other drugs.

So, we look forward to hearing more from that. And I can't remember the third component of your question.

Yeah, I'll take that François. I'll just add one thing to what Dr.

François said on what he said to this time, it's important to understand that the agency certainly has the authority to conduct an inspection in a variety of different ways. And, you know, keep in mind, to that, like for example, this plant has been inspected by the Korean authority.

So, maybe that's something that can help, we don't know. But bottom line is we're going to try everything we can, and it's good news that in unprecedented times, they're looking to change the way they do business, because you kind of have to.

And I want to stress another thing, we are absolutely ready for this inspection. We are ready for a long time, we welcome it.

Matter of fact, the third part of your question was the mock inspections, was it required? They're certainly not required by the agency.

We do that to make sure we're ready. And I can tell you, we have Spectrum boots on the ground there, we have Hanmi, which I mentioned, is a world-class manufacturer with a world-class plant.

Their people are ready, and we work very closely with them with these mock inspections. And we have a third leg to the stool, we have outside experts, we've hired to run these, not only run these mock inspections, but also help the readiness.

And these are people who have done this for a living. They do this – they know exactly what the FDA is looking for in an inspection.

So, we feel we're ready. We welcome the inspection already, you know, we can't wait.

Got it. It's all really helpful perspective.

And second question was on the pre-NDA meeting, just wondering if you can provide some insight into the case that you're going to make to try to persuade FDA, I guess, will it include post hoc analysis in reconciling data from Cohorts 1 and 2, or will the argument be more around having FDA factor in new data from Cohort 3, and Cohorts 4 through 7 as you get the data from those additional Cohorts?

Sure. Well, obviously, we're pleased that Cohort 2 and you know met its primary endpoints, and that's the critical ingredient that you need to have a discussion with the FDA.

So, our request to the FDA, as I indicated in my remarks, is that we're seeking – a period of first approval for that particular indication for that cohort, which is in previously treated HER2 exon-20 mutation in non-small cell. Those cohorts were all pre – as pre-specified endpoints they're all independent.

The FDA had agreed to that. So, a positive outcome in Cohort 2 is not in theory, not affected by, you know what happens in Cohort 1, 3, or 4.

So, you know, that's the good news. That's what we're asking at this time, and obviously once we've had the meeting which will be soon.

We will update you on the outcome.

Got it? Understood.

Thank thanks for taking my questions.

Sure.

Thank you, Maury.

Hey, Michael.

Hey guys. This is Charles Zhu on from Michael Schmidt.

Thanks for taking the questions. I had a couple regarding poziotinib, I guess, the starting off, the ZENITH20 Cohort 3, that should be reading out by your-end, given that this is a less heavily pretreated population relative to Cohort 1, how should we think about, I guess, patient willingness or ability to tolerate [indiscernible] side effects at the 16 milligram dose?

And what could this mean for those interruptions, discontinuation, or overall drug exposure? Thanks.

Sure. Look, we – and until we see the data and present the data and share the data with you, at least the top line data I can't presume at this point of what we're going to see totally in the safety profile.

Clearly, we monitor safety on all our studies, including these cohorts, and, you know, for signals that would be out of the ordinary, and as you know, we have not, you know, had to make any announcement of that sort. So, we're going to have to wait for the complete analysis that, you know, it's not that far away, or we're saying you're going to have it before the end of the year.

Got it. It makes sense.

And then my next question is on Cohort 4, in treatment-naive HER2 patients, I think you made some prior commentary around this cohort, having a mix of patients either receiving the prior 16 milligram once daily dose, as well as more recently enrolled patients receiving the BID dosing. I guess, on this front, my question is, if the alternative dosing schedule doesn’t de-result in a different clinical profile, how would clinicians or the FDA interpret the results coming out of the scope of given that it is independently powered?

Thanks.

Yeah, sure. So, you're absolutely correct.

Cohort 4 was started at 16 milligram once a day. and you can think about it in the sense that probably roughly after the patient originally intended more – enroll at 16 once a day, the – currently we're dosing patient at 8 milligram BID, as you can imagine, 8 milligram BID is 16.

So, we're still dosing at 16, but we are administering it twice a day, you know, 8 BID. So we think actually, that will be helpful for us to understand better in that pivotal, arm or cohort.

You know, is there a difference between when you give 16, but if you give it once a day versus twice a day. So, we think that could play in our favor.

And we are – we have plans to continue the enrollment for a full 70 patient at BID, if necessary, but as we've indicated, we are going to be meeting with the FDA in the near-term, and we'll have to gauge with them what they would prefer we do here, but from our perspective, you know, we're dosing patients in Cohorts 4 at 16 milligram per day.

Got it. Thanks for that clarification.

You’re welcome.

Hey, guys, thanks for taking my questions. Maybe a couple.

You know, can you give us like any kind of more detailed color on how you're thinking about potential timelines of being able to [kind of thread the needle] on a re-review at Hanmi. Also just can you talk a little bit about your confidence of a broad ROLONTIS label?

And then lastly, just can you just talk a little bit about like, since Cohort 3 is coming up pretty quickly, why not maybe just wait and have a dual conversation with the FDA or is it just you know, generally, you kind of want to do these in sequence, because you just don't know when you can book the meetings. Thanks.

François, do you want to take that or?

I'm sorry, I – can you repeat the question? I think, I wasn't …

Sure. So one is like, on the estimate around like, kind of can you give us a tired view on the timeline for ROLONTIS like, you know, do you think it’s six months?

Do you think it’s six weeks, like, I know it's hard to tell, but just in your best guess, you guys must have a [basic]? Second one, your confidence on potential broad label for ROLONTIS?

The third is on poziotinib at I just wanted you to talk a little bit about why not wait for Cohort 3 data perhaps, you know, in addition to Cohort 2 and then go to the FDA? Thanks.

So, the first question is on ROLONTIS, when do we expect the inspection? Is that correct?

Just like if you could give a little more color on the timing, like, is it months, weeks, like…?

So I think Alethia, I would agree with you that it's hard to tell. I think we've told you as much as we can.

And as I've just mentioned, you know, the FDA, release yesterday to the Pink Sheet that they were looking actively into virtual inspection. I don't know how and when that will occur.

And we don't have information at this time, obviously, we're actively, you know, working to try to make sure that we're ready, as we've indicated, but as well, we are, you know, following up with the FDA to make sure that, you know, they understand how important this is for us and patient.

On that part and that question Alethia, I'll just add two things for color. We are not going to sit around, we want to try and do what we can to push this forward or nudge it, I’ll tell you that.

We’re not going to just sit and wait, I can assure you that. But secondly, I'll just mention the pandemic in South Korea is doing very, very well.

I just, you know, we update with the Hanmi team quite often, and they were saying they're down to like 100 cases a day, in the whole country. They’re really way down.

So, I'm hoping that plays to our favor. And maybe we'll I believe and do it live, but otherwise, it's good to see the agency moving forward and realizing, hey, like Europe is still – and we've got to, just like we're doing in all our businesses.

We have to get better with doing these in another way. So, we won't sit back.

We’ll try and nudge them anywhere we can, and we'll work with them aggressively to try and do whatever we have to do as will Hanmi. So again, I wish I can give you an exact date.

But that's the best we can give you. But François you want to go ahead with the broad label for ROLONTIS and also the pozi waiting [for three] on the other two questions.

So the labeling discussion, I don't think we can get into the details of it. I assume this is labeling for ROLONTIS because, you know, obviously we're going to have to wait until – normally when you have a review of a BLA or an NDA, one of the last thing you do once you, you know, that answered all the questions, you get into a discussion about the label.

So, I've communicated and shared with you that we have been in those type of discussion. So that's a positive from our perspective.

Clearly, we still have this inspection issue that, you know, we think we'll get addressed in a timely fashion, but you know, we don't have an exact date. On pozi specifically, Alethia, can you repeat the question?

I mean, Cohort 3 is not far behind, and like, you know, if it hits, it might strengthen your argument with Cohort 2 why not just wait and have that meeting in the first quarter, maybe rather than immediate?

Well, I mean, you know, what I can tell you is that, we had agreed, you know, Type C meeting, we agreed with the FDA some time ago as to what we needed to do to declare victory on a Cohort and we've achieved this. So, we're not going to wait.

We're going full ahead. As we've indicated to you, you know, schedule, we're going to have the meeting.

Clearly, we have shared with them the timelines around all our cohorts, and they are aware that Cohort 3 and 4 and – they're also aware of our exploratory Cohort 5. So, you know, they're fully aware of all that.

And at the meeting, I'm sure it's going to come up for discussion. And if they want to see it before, well, you know, we may do that, but you have to remember, they're independent, though.

Cohort 3 positive or negative should not influence Cohort 2 here.

Okay, great. Thank you.

Thanks Alethia.

Hi, Ed.

Sorry. Hi guys.

I was on mute. So thanks for taking my questions.

I have a few. First, on the ROLONTIS launch, last quarter when you were getting ready, you said you were looking at hiring in about 60 FTEs before the launch.

And I think you had commented that 21 were already hired. Are you continuing with your hiring now?

Are you getting closer? Are you putting it off until you hear more about the timing to potential approval?

Tom, you're leading now. Why don't you answer that?

Hi Ed. How are you?

So, your recollection is correct. We currently have 21 of the 60 FTEs and the remaining FTEs are gated to that PAI being scheduled.

So, the 21 that are onboard are really focused in the [indiscernible] area, market access national accounts and field leadership. So those folks are actively engaged in our preparation efforts.

We want to make sure, we're on the ready and can pull that trigger in-line with the FDAs inspections. So, we want to mitigate our [indiscernible] spend for the remainder of the customer facing staff, but we do have the 21 FTEs that are actively finalizing our preparation efforts and will be ready to go when the agency gets to the facility.

Great. Thanks, Tom.

And so maybe a couple of questions on pozi, one, François just for the Cohort 4, you know, when can we expect to see data? And will that data be on 70 patients at the [16 milligram] or is that going to be data on 70 patients at that 8 milligram BID?

I mean, they are both [16 milligrams], so I'm just wondering how to think about the data and the timing?

Yeah, so we – on the basis of the pharmacologic modeling the fact that we had seen in Cohort 1 and 2, some, you know, fairly I – dose interruption and dose reduction, we decided that we would explore some other way of giving the drug and the data is coming in as we speak, if you want. So, the original ends for Cohort 4, I believe with 70 patient and we were half enroll, maybe a little more than half enroll at 16 once a day.

And, you know, we're going to, we are currently on track to add 70 patient BID on Cohort4. So, in other words, the same assumption would stand.

We will discuss with the FDA at the pre-NDA meeting. If they, you know, continue to agree with what we're doing or if they would prefer for us to do otherwise.

So, I can't answer you today. Other than say, we will have definitely more than the original end at 16 milligram, you know, one way or the other.

And if we need to go back to 16, we will do it after, you know discussing the matter with the FDA.

Okay, thanks. And maybe on Cohort 5, you know, you mentioned you have over 100 patients to date, and you stopped the 10 milligram dose as sub-optimal.

I'm just wondering, now looking at the 6 milligram and 8 milligram BID dosing, where do you stand for the number of patients? So, you know, when we do see data, and if you have any timelines on when we'll see data, but, you know that would be appreciated, but how many of them were in that 10 milligram dose that was suboptimal?

Yeah. So, we you got to remember Cohort 5 started by randomizing patient to 10 milligram, 12 milligram, or 16 milligram once a day and then we amended it.

It stopped enrolling at 12 and 16 once a day, and more recently, we've been randomized patient at 10 milligram, 12 milligram and then the BID – I'm sorry, not the 12. The 10 and the 6 and 8 BID.

So, you know, we're – so that's what I'm reporting to you here that we have 110 patients. The reason that we're mentioning the number is simply because a number of company have, you know, indicated that COVID had affected negatively their enrollment, and we did see a, you know, a transient impact on our enrollment, but you know, it's going pretty well now.

And the fact that we have stopped 10 milligram, and we didn't issue a number, but let's just say that there's enough patient for us to make a decision as to that, you know, some certainty around the 10 milligram dosing. And, you know, we will obviously have what we need, in terms of the BID dosing.

The exact time of giving you information, though, probably be before the end of the year, we'll be able to make comments, mostly on the safety side, as you know, efficacy takes a little longer, because we want to assure not only responses, but the durability of response. So, you know, we're going to update you in the next two months on what's going on, what we're seeing in the various dosing cohorts and including some preliminary information on the BID.

Okay, great. And maybe just last question for Kurt.

That $8 million for the drug substance that was tacked on to the R&D expenses this quarter, will there another charge for drug substance, you know, next quarter or, you know, is that really hit and we go back to the run rate without that? Thanks.

Yeah, thanks, Ed. So, we, you know, we had started and continued to be manufacturing product, you know, as we exited the third quarter into the fourth quarter, so there will be some expenses for ROLONTIS drug substance in the fourth quarter.

I can't give you a number on how big that will be, but as Joe kind of mentioned, we are going through a process right now in evaluating every piece of spend that's related to ROLONTIS and making sure that, you know, is this an activity that needs to happen now? Should it be gated?

When should it happen? So, we're going line-by-line to our budget to make sure that we're going to be prudent with our spending.

So, you know, short answer is there will be some spending, but we're taking a hard look at manufacturing and figuring out exactly how much we need to go do? We obviously want to make sure that plan stays in a readiness mode.

Okay, thanks Kurt.

Thanks Ed.

Hello Reni.

Hey, good afternoon, guys. Good afternoon.

How are you? Couple of, I guess a couple of questions.

You know, I should probably know this, but how many products does Hanmi manufacturer worldwide? And I guess, how many are in the U.S.

and has the manufacturing plant been inspected by the FDA before?

How many – I can't tell you exactly how many, they have multiple products in South Korea and other places in Asia that I can tell you. It's a full-fledged manufacturing.

They started out for a long time as a generic company, manufacturing generics. And then they expanded several years ago into drug development and that's when we got involved with them and got both drugs actually, as you know from them.

They don't have any drugs in the U.S. today, but they were inspected.

My understanding was for a device with the U.S., but no drugs in the U.S. at this time, but certainly several drugs that they have throughout Asia.

Got it? And when you mentioned that, you know, there were activities that you're gaining to manage the cash, of course the delay in hiring the sales force, you know, for sure.

Is there anything else that you are actively managing, at least from, I guess from [a want this], you know, rollout perspective, you know, that we should be aware of?

Yeah, Reni, this is Kurt. I think the key things here would be, you know, mostly focused on the commercial side of the business.

So, as Tom mentioned, on the sales team, you can think about some pre-launch marketing spend as well. We're going to make sure that we maintain a state of readiness for the facility.

And you know, François also spoke a little bit about some of the continued development efforts that we have with ROLONTIS and those are some activities that will continue.

Okay. And then just one final one on ROLONTIS, we're off as performers [indiscernible], what's the kind of cadence of discussions with the FDA right now?

Because this is, I think this is like one of the first times I've heard of a deferral, you know, is there a back and forth or do you just kind of have to wait until they get back to you?

François you can add to this, but obviously, you know, we're not going to sit back and wait. They have the authority to do things.

So, you know, like in anything else, you contact the agency, they have so much time to get back to you. Kind of that's all laid out.

And then we you know, we certainly can have discussions on what's next, how can we work with you, we're willing to do whatever it takes. As Dr.

François said, just yesterday, they issued, you can see movement on their part for the first time in this because this is new to them. And they issued the statement on moving forward.

Europe's doing it, as you heard already. So I think they're going to have to just start moving forward.

And all I'll tell you is, we will do anything we can to, I’ll use the word nudge them. You know, you have to do it properly, but we every right to talk to them, we're ready to go and try and figure out how to do this as quickly as possible.

Got it. And then just one… go ahead.

Look, they’ve given us the deferral. We have had, let's just say some representation to them to seek clarification.

I'm not going to get in. I'm not going to get into details of how many communication etcetera, but clearly we're working closely with them.

Obviously, it's a problem. We're not the only manufacturer here who has that problem, and the FDA is very aware, as I've indicated, they’ve issued some new information about development of guidance yesterday.

So, we think it's a very active topic, subject. And clearly, we will, as Joe has stated, we will continue to, you know follow up with them as to what to expect here, especially in timelines.

Got it. And just switching gears to pozi real quick, you know the FDA meeting that's coming up, I may be incorrectly just assume that, you know, with the trial being a registrational study, and the endpoints kind of agreed upon that, there likely wasn't, you know, much more discussion needed until you just kind of file the application.

So, what exactly, I guess the long winded way of asking, what exactly kind of looking for here, what additional clarity Do you think we could we could possibly get?

Yeah, so this is standard – whenever you think you're going to file an NDA or BLA, it's usual to call a meeting with the FDA, and then you go over either your plan, like you agree on the data set. So, I'll give you a specific example.

We obviously would provide the efficacy and safety on Cohort 2, but the question would be, for example, okay, how much additional data on safety did they want to see? Did they want to see all human exposure?

For example, in our case, that's over 1,100 human beings whoever receives the drug. So, we have an extensive database of safety.

We need to know from them, do they want to see all the studies that we have done that our partner has done? Did they want to see?

So, you know, it's details like that. Then, you know, you have preclinical work, like, safety, toxicology and animals.

We clearly have done quite a bit of it. We need to know, okay, do they agree that, you know, what we've done is what they want or they want something else.

And, you know, then you go to pharmacology, and so anyway, it goes on and on. So, and then you can ask them very specific question about you know, anything in the submission, then you agree on the format.

As you know, there is for these mutation driven tumors, you need to develop a companion diagnostics. So, you know, you have to come to an agreement with them as to what kind of companion diagnostic you're going to have, etcetera.

So, there's lots of questions. And that's what we're going to be discussing, but there's nothing unusual.

This is standard for a pre-NDA or pre-BLA meeting.

Yeah, Reni, our goal is to [indiscernible].

Thank you, guys. [Indiscernible]

Hi, Mayank.

Hi team, thanks for taking my question and resilience is the appropriate word. And I understand you're very far from being done for the year.

So, my first question, if I may on, you know, the term you used about pozi dosing strategy update by the end of the year? Could you just talk a little bit more in detail about that?

You know, I think you said that in the context of Cohort 4 and I’m trying to understand if your Cohort 3 does not have, you know, the kind of limitations we saw with Cohort 1, I mean, you can really, you know, move along with the [16 mg] dose with a higher confidence level through the rest of the program. So, I'm just saying to, you know, connect the dots in follow up to all the questions have been asked before, and try to understand what can we learn from you by the end of the year?

You know, that boils down to a pozi dozing strategy update.

Sure, let me try to address that. So, let's start with Cohort 2.

So, Cohort 2, we had agreed prior to doing this study. We had agreed with the FDA as to what we needed to show to make it a meaningful outcome.

And we have met that. So that was done at 16 milligram once a day.

So, in other words, you have a positive trial at a 16 milligram once a day. So, and that is the – that is the main discussion point for the pre-NDA meeting.

In other words we’re saying look, we had an agreement, we’ve met what we needed to do, and now we would like to discuss, you know, what kind of data do you want to see, etcetera? And then the dosing strategy, it’s simply because we knew, in Cohort 1 that we had analyzed before Cohort 2, we knew that we had a fairly high level of dose interruption and dose reduction.

So, we decided we did some [Technical Difficulty] modeling, and we decided that we probably could reduce what's called a Cmax, and still stay above the [EC-50]. So, in other words, it's not that 16 once a day doesn't work, it's just that we may be able to improve on it.

And that's why we're doing the BID, and we'll provide data in near term, but also, we have looked at 10 milligrams a day, 12 milligrams a day, simply because we know what dose, you know is effective, and as some degree of toxicity, and that's 16. But what we don't know is, what is the minimal effective dose, like how low can you go?

In other words, you might be able to reduce some of the toxicity, but still maintain anti tumor activity. And what we've announced to you today is that 10 milligram as a starting dose, is just possibly a little too low to start.

In other words – and has to be higher than that. So that's great news.

I mean, we're learning what is the minimal effective dose, and remember, we have done 12 milligram. We have data that's maturing, and we and we have 12, once a day, and we have 6 and 8 BID that will be maturing as well, right?

We're enrolling. We need more data and a little more time to analyze that data.

So, all of that together will obviously be discussed with the FDA. They will see 16 once a day works, and they will see that maybe we can improve on it.

And we'll have that discussion with them. I hope that answers your question.

It does and I really appreciate you laying it out. So, you know, just to clarify, so we'll have some sort of apples-to-apples, you know, same population data between 16 mg once a day and then 12mg once a day and then also 8 mg BID at some point, you know in first quarter or by the end of the year, is that fair?

So I think what I said is, we're going to definitely be able to make some statement about safety, the efficacy, you know, you have to follow patient longer. So, we may not, you know, we're not going to have final analysis on the efficacy on some of these Cohorts in the next two months because we have to follow patient longer, but you know, we will get a very good indication of, if we're on the right track with BID.

Yep. And safety is obviously the most important question because we know the drug works.

So, then my next question on ROLONTIS same day dosing, could you just give us a little bit color? It seems like it might be important for, you know, commercial purposes.

So, could you just remind me, how does that fit in your, you know, longer-term plan of including your differentiating against biosimilars?

Joe, I assume you want to take that.

Yeah, it broke up. Could you ask the question again?

I was trying to make sure I answer the right question, it kind of broke up. I'm sorry, Mayank.

Sure. Sure.

No worries. On the same day dosing for ROLONTIS, I was just curious, two parts to the question.

One is, how does this fit in your longer-term plan to you know, compete in a in a market that will have biosimilars? And then the second part of the question was, you know, what do you expect to learn before the end of the year that will, you know, really give you confidence that, you know, you really need to run with this formulation, and again, keeping the commercial implications in mind?

Yeah, okay. First, first of all, let's – just to make sure I clarify.

The trial is – that we did to face the reason, and we're trying to get – a label that is non-inferior, I want to be clear on that, as you well know, [indiscernible] so that that'll be the launch label, so to speak. What same day dosing would be, would be expanding the label down the road, and Dr.

François was saying is, is by the end of the year, we'll know if we get to expand this and go further with a bigger trial to try and get something like that on the label. We would launch without that and what having a say, the dosing would mean.

And I can tell you that in the past, other companies have tried to do this and it didn't work. What the advantage would be is, now what happens is, when you get your chemo, the next day is when you get your white blood cell factor, you can't do it the same day.

It would be a tremendous advantage and a differentiating factor from all the other white blood cell factors in the market today, the biosimilars and the innovative product. If our product worked, and we were able to say, listen, this is the one drug you can give your chemo and on that same day inject the patients, the nurses, the patients, and the physicians would really love that and it would be a point of differentiation.

So what François was saying is, later this year, we'll know where we go with the program. I think François is that all you want to say on that part of it?

Yeah, no, exactly. I mean, the submission that we have in front of the FDA that, you know, we're waiting for the inspection of the plan, as you know, what's called traditional dosing, which is you give the growth factor the day after the chemotherapy.

And, you know, so that's what the data that was positive and in front of the SBA. Separately, because this is not a biosimilar, and it has difference in what's called pharmacodynamic that means that that particular – our drug ROLONTIS goes preferentially to the bone marrow, and stays there longer.

So that opens up some opportunity for us. So the first, you know, we are exploring, can we leverage those pharmacodynamic advantage?

And we're trying to give the drug the same day. So, it's important for management of patient, but obviously, we need to test this and that's why we're doing.

We're in the process of testing that and that would be a very important differentiator, but it has nothing to do with the current submission if you want, and the approval that you know, we opt to obtain very soon. This would be further down, you know, modifying the BLA later on.

I understood, thank you. And my last question, just quick reminder on the status of the Phase 1 open label study in lymphoma patients is that up and running or is that impacted by COVID?

Yeah. So, you know, we – good question.

So this is obviously an early asset, so as you know, we have discussed today, we're obviously very focused on our late assets. But nonetheless, we remain very excited about the [fifth technology].

We've had a number of regulatory hurdles that we had to resolve, you know, updating various documentation, and as we are going forward here at sites, we had to deal with COVID-19. As you probably know, most IRB and many centers, you know, are dealing with COVID-19, and they're not particularly enthusiastic right now about the new Phase 1 study.

We're getting there. We're making progress, but it's obviously a lot slower than we want.

Great. Thanks for taking my questions.

Sure.

Thank you, Mayank.

Thank you, operator. And listen, this concludes the call.

I want to say thank you to everybody for your interest in Spectrum. And if you have any further questions, please feel free to contact us in between.

And again, I'll mention we'll be dealing, being part of some upcoming financial conferences that we hope to connect with many of you at ease. So, with that operator, we’ll conclude the call.

I'd like to say thank you for everybody's interest in Spectrum.