Q1 2021 Epizyme Inc Earnings Call
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Today's conference is scheduled to begin shortly please continue to standby and thank you for your patience.
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Hello, and welcome to Amazon's Conference call at this time, all participants are in a listen only mode there'll be a question and answer session. After the prepared remarks. Please be advised that this call is being recorded at episodes for questions I'd now like to turn the call over to Dale Saturday June you may begin.
Thank you operator this morning, <unk> issued a press release, providing a business update in addition to first quarter 2021 financial results.
That press release as well as slides to accompany today's call can be found in the investors section of the company's website at <unk> Dot com.
On the call with me today is Rob bays, Moore, President and Chief Executive Officer, Paolo on Betsy Chief Financial Officer, Vicki for Qunar, Chief Commercial Officer, Matt Ross Executive Vice President and Chief strategy and business out there and Doctor should Folly Agarwal Executive Vice.
Didn't and chief Medical and development Officer.
As a reminder, today's discussion will include forward looking statements are related to episodic current plans and expectations, which are subject to certain risks and uncertainties.
Actual results may differ materially due to various important factors, including those described in the risk factors section of our most recent forms 10-Q, 10-K and other SEC filings.
These forward looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date, we undertake no obligation to publicly update these statements.
At this time I would like to turn the call over to Rob based more Robert.
Thank you Bill and good morning, everyone.
Right to be here with you to provide an update on our Q1 results and how we see our business progressing this year.
As we moved from March into the second quarter.
We began to see some very encouraging signs that things are slowly beginning to return to normal for.
Even a bit earlier than we expected.
Vaccinations are now much more broadly available.
Officers report that Theyre busier and they are starting to see more patients than before.
At the end of March we ease the travel restrictions for our vaccinated field based employees and are allowing them to travel again to reach their customers for in person discussions and the institutions in the offices that allow us.
Some accounts have reopened to representatives, calling on them. Although this is still more the exception than the norm.
And so on educational program and just beginning to return to in person like regional medical conferences.
All of this is happening slowly and it's happening in pockets of the country at very different rates.
It is encouraging to at least begin to see these changes.
However that was not yet the case for Q1 of this year, but we were still dealing with a second wave of infections that started late in 2020 and resulted in the extension are heightening of restrictions in some areas.
As a result in Q1 up is on continued to execute almost entirely virtually as we had been previously and.
On the significant challenges, we experienced last year due to the pandemic persistent.
Despite these challenges we continue to build positive momentum on the metrics that we have control over that will ultimately be important to test the Eric adoption.
Slide for us on awareness for the number of accounts prescribing.
On continued broad unrestricted access as coverage was renewed at the beginning of the year.
We continue to see quarter over quarter and month over month growth for Tesla, Eric adoption with March 2021, representing the most successful month, yet in terms of Tandberg bottle sold.
Total revenues for the first quarter were $7 6 million of which had net revenues in the U S for $6 2 million or 37% increase over Q4, 2020, which was driven primarily by increased adoption in follicular lymphoma for F. L.
Epithelioid sarcoma or Es sales continued to contribute to total revenue at approximately the same level as Q4.
Commercial bottle demand increase quarter over quarter by 31%.
For the remainder of the revenue booked in Q1 was collaboration and other revenue of $1 4 million.
In early March up is on hosted a strategic vision calls entitle the next episode.
Where we unveiled our strategy for how we will create value for patients and the physicians who treat them at the time shareholders for the next five years.
I encourage you to listen to the event webcast. If you haven't already but to quickly recap. This strategy for long term growth relies upon our execution across four pillars.
Obviously, the first and most important focus in the near term is maximizing our commercial effectiveness to ensure adoption of pets Derrick amongst many eligible S. L E S patients as possible.
Including our development efforts to bring tests Derek into earlier lines of therapy by combining with other agents or as monotherapy.
Second continuing to build on sales pipeline in the drug potential, including moving our programs into additional solid tumor and Hematological malignancies and.
And produce a steady stream of data over the next five years and beyond.
Third expanding our pipeline and portfolio beyond Ted Barrett for.
<unk> novel epigenetic therapeutics into clinical development.
And for leveraging all available options to expand our patient reach and increase shareholder value both resource Lee and responsibly.
In the first quarter, we made good progress across these four pillars.
As I mentioned earlier, despite the COVID-19 headwinds persisting in Q1, we continued to build momentum on metrics needed to ensure accelerated adoption once the pandemic challenges begin to subside.
On the clinical side during our vision call, we outlined a comprehensive and innovative clinical development plans for tests Barrick.
For which we anticipate a steady stream of data beginning in 2021 and over the next five years.
And we highlighted some encouraging early data from the second line FL and prostate cancer studies.
We plan to further explore tazemetostat as both monotherapy and in combinations across multiple new hematological and solid tumor cancers, and two basket trials, which are on track to initiate during the second half of this year.
Finally, our novel <unk> inhibitor, which addresses the long sought after pathway and was introduced during the vision call remains on track for planned <unk> submission mid 2021.
I would now like to turn the call over to Vicki <unk>, who will provide additional color on our Q1 progress and Ted Barrick adoption in <unk> and then <unk> will provide an update on our Tazemetostat development efforts.
All about pallet, who will briefly review our first quarter financials before we open the call for Q&A.
Ricky.
Thanks, Rob and good morning, everyone cash.
<unk> continues to gain traction, while we navigate the unique environment presented by COVID-19.
Adoption is steadily increasing and we saw sequential month over month growth with March representing our highest demand to date.
We continued to add new prescribing accounts in both the academic and community setting increasing 38% in the first quarter compared to Q4 of 2020.
Aided and unaided awareness among our ethanol treating physicians improved and <unk> continued to lead in share of voice related to other therapies in the <unk> space.
Cadbury aided awareness among our physician is now over 70%, which is in line with other agents that have been on the market for years and our market research suggests that physician intent to prescribe remains high.
Commercial bottle demand with 31% in the first quarter compared to fourth quarter of 2020, while total revenue grew by 37% for $6 2 million.
We didn't see any changes in payer coverage policies at the start of the year and as we expected there was some transition from patients utilizing our patient assistance program, because I know in the fourth quarter the commercial patients in the first quarter.
As a result of our efforts.
For Keith is coming from all lines of relapsed refractory therapy in both Follicular lymphoma, and epithelioid sarcoma.
With NFL the largest growth in share has been in the third line and later treatment setting and we continued to see some utilization in second line <unk>.
And 60% of our sales now come through the specialty distributor channel, we have limited visibility to utilization split by mutant and wild type of untapped debt. However, based on market research. We know that we are seeing utilization in both.
As Rob mentioned <unk> sales for patients with Es in Q1 contributed at the same level as Q4, we continued to see new patients start therapy in the first quarter. So some of the early patients treated in later lines of therapy cycled off treatment. Our focus for this year is on gaining broader adoption of pads, Eric and earlier.
Your line in order to provide the most benefit for patients living with debt extremely rare disease.
As we alluded to on the fourth quarter call in late February the environment. We operated in during Q1 did not substantially changed from the end of last year.
The two distinct challenges that have persisted early this year include first.
Decreased frequency in patient visits to their treating doctor following the onset of COVID-19, which has been accentuated the net fell compared to other cancers did the inherent nature of the disease and the general age of the patient population.
And second our field team limited face to face access to treating physicians on their staff.
In the first quarter data have shown that extra on new patient treatment starts on any therapy remain depressed approximately 20% to 30% compared to pre COVID-19 level consistent with the fourth quarter.
While secondary data sources has yet to confirm that the epidemiology of FL has fundamentally changed.
Results for COVID-19, the number of patients receiving any new treatment has been suppressed now for many months.
We do anticipate that as vaccinations continued to increase patients will slowly return to in person visit and expect we will see new treatment starts begin to rebound.
We are beginning to see positive signs that the opportunity for live customer engagements are improving and are happy to share that following vaccinations and appropriate consent, we have eased restrictions and allowed our field team to travel again and does it accounts in person wherever possible.
This is particularly encouraging because it has taken more time to get traction with physicians virtually than might otherwise be the case in person and compounding. This while our approved label allows for very broad use of <unk> in patients with relapsed or refractory FL. It can require explanation to prescribers given.
The two distinct indication statements.
We expect that improving direct access to our customers will particularly benefit our ability to properly define the use of tests Barrick and earlier treatment line and easy H two wild type patients.
We continued to see an increase in new accounts prescribing has barrick and new patient starts in Q1 at the same time, we have also seen some patients discontinue their therapy within the first few months of treatment.
There are a variety of reasons for why this may occur, but some of it appears to be driven by later line treatment where patients quickly dropped off therapy. We saw the same phenomenon in our phase II clinical trial as you might expect with any new launch in oncology for patients most in need of new treatments are often very late.
<unk> stage with high disease burden and they've been through many other drugs.
In order to ensure that physicians utilize test barrick in earlier patients in need of new treatment. We recently rolled out marketing tools to assist our sales team with identifying the most appropriate patients for <unk>.
As physicians continue to gain experience for <unk>, particularly with using because they are earlier in their treatment journey, we expect duration of treatment and satisfaction with the drug on true enhancing adoption as a result.
Overall, we're encouraged with the field team's performance and reaching physicians and driving awareness for cash Zurich under the current circumstances as.
As we continue to gain feedback from our customers. We see that physicians are increasingly more likely to test for each two mutational status as part of their patient treatment plan.
Market research indicates that approximately 60% on physicians now test for each H true, but they're not testing and everyone. We're still only about 37% of FL patients being tested it's.
It's also important to note that easy to testing is often being done at diagnosis or.
Before initiation for their patients first line treatment.
While most physicians have access to next generation sequencing the other institution or other commercially available panel around one quarter of physician noted that they would like to test and we'd like to have an easier way to do so.
Physicians are interested in understanding easy to mutational status for multiple reasons, including a better understanding of the patient's cancer and helping set expectations with patients once prescribed <unk>.
We will continue to support that physician community with regards to their inquiries around testing and providing unique solutions to make testing easier.
Looking forward, we are confident in our ability to execute commercially and continue to find ways to expand the adoption of cash Barrick.
We are optimistic that with broader vaccine rollout, we will have more and more opportunities to engage face to face with our customers.
The patient physician interaction will also began returning to normal.
At this time I'd like to pass the call. This for Folly, who will provide an update on our ongoing clinical trials and development plan I look forward to addressing your questions during Q&A.
<unk>.
Thanks, Nikki and good morning, everyone.
During the vision cause we shared preliminary safety and activity data from a consummate. These phase <unk> study is a clear pathway Inc.
Combination with us that there are lots of attracting participation. That's the lights on released proposed that this could be a meaningful combination approach for treating patients in the second line on later.
As a provision calls on the total inflation and dose in the study on.
Our southern Nevada patients responded to treatment with three patients having a complete response and for patients having a partial response.
DSD for himself and adverse events with consistent with the safety profile of the individual Inc.
We plan to provide an update to the 50000 datasets at the Ash annual meeting later this year that we expect to have additional data on the patients treated and the follow up.
As a normal procedure of any safety study.
After completion of planned enrollment of the 57 day stomach as opposed to cause the selected recommended phase two dose for the FDA for debt of here.
We are aligned with the agency on an important change to the protocol to allow for the potential efficacy readout at the second interim analysis.
Once we have the 55% of PFS events in the phase II portion of the study.
On opportunity to conduct an efficacy analysis and the second income as long as the pay defined treatment effect in the protocol as it cheap.
Net provides an opportunity for stopping the study early and data availability earlier than the completion of all PFS events.
Although the selection of the 800 milligram dose as an Aussie Treaty was endorsed by an extended 50 company and scanning for imaging during the W. The agency requested additional those optimization efforts to support initiation of the randomized phase two portion of the E. P. S. T O two studies.
This was to ensure that is well characterized the effect of combining tazemetostat that ask that given that day in adult only a small number of patients on to date since we observed no dnp's in our pes despite stays on beta site.
Based on these discussions with the agency episode has expanded from B cohorts of 600, Mcdonough D. I T and 800 milligram B I D to include a minimum of 15 patients total total.
Which will allow for the collection of additional patient data at these doses, including PK exposure safety and efficacy.
It's important to note that at flat for additional patients at these two dose levels.
It's on center mute eslick dose optimize and not for any particular concerns of safety signals observed in the safety gentlemen of the easiest senior to study.
Due to the fact that we have continued to enroll the study we have nearly completed enrollment for those two cohorts the debt at fly fishing on but at both the dose Netherlands.
<unk> by the agency.
Once it is why data has been collected and analyzed after three months of other real promptly submit their findings to the agency.
In the meantime, we continue on efforts to complete all operational startup activities for <unk>.
The initiation of the global safety study to minimize the impact of the study enrollment completion.
We expected for updated safety and activity data from the 50000 and at Ash later this year.
Separately studies, such as E. P. S 14 O one evaluating tests a day.
Then in the relapsed refractory FL.
For LIFO sponsored trials evaluating Castlerock and front line highest F L and deal Bcl.
And the easiest one concentrate to study it.
E S continue to move forward as tight range.
Look forward to sharing 15 preliminary activity data related to easiest tier one study as part of a poster presentation that asphalt in few weeks.
Additionally, our true propose basket study evaluating multiple combinations the test in both Hematological and solid tumors remain on track to be initiated second half of this year.
We also continue to work with E. On me to define the registration path for test for it in Es and FL in Europe and.
To have alignment by the end of the pit.
During the mission cause he also provided an update on data from the phase <unk> study of Tazemetostat in metastatic castration resistant prostate cancer on Mci SEC called easy at 11 O. One.
In the safety that in portion of the study the protocol allow patients for doors, let's see let's see sales until it might aperture on for installation and Danville chipset for therapies are shocked with chemotherapy.
In this study patients received either other tranches tazemetostat plus prednisone on.
Insulet and lifeless tazemetostat.
In this population of prostate cancer patients for the need for new options. Besides chemotherapy substantial we are encouraged by the early data we have generated quite a journey in combination with <unk>, where we saw six out of 13 patients at the PSS. If you just pause.
Just dose patients having a decrease in the BSA upgrade then for.
50%.
Also highlighted one patients particular, other investigators and from peers with a fetus pause after assuming tazemetostat and until the device also has it been from day to go after this path for the 26%.
And Todd admission Demeter, Inc.
Accordingly, we are on a list of combined both the drug without any additional safety concerns and the phase two dose of pleasant everybody's on CIB, Inc.
Sales to a portion of the study.
I'm betting on Suezmax alone lessons and Susan My plus Tazemetostat is actively enrolling patients and we expect to share updated based on the data on the patients treated and longer follow up at a medicine for instance, later this year.
Lastly, we introduced on knowledge <unk> inhibitor during a division called <unk>, which remains on track for Uptime 90 submission mid 2021, and I intend to move into the clinic by year end.
We are planning our first in human trial in relapsed refractory <unk> and multiple myeloma, they dose escalation to evaluate a maximum tolerated dose and status to a proof of concept in three cohorts, including T for 14, relapsed refractory multiple myeloma.
Non people 14, relapsed refractory multiple myeloma, and then lots of factors going into this year.
And the near term, we look forward to sharing pre clinical data on <unk> at the European Hematology Association Congress in June.
At this time I'd like to pass the call to Paolo <unk>, who has the view on first quarter financial results follow.
Thank you Stefan and good morning, everyone.
We ended the first quarter with 298 for $9 million from Egypt, and cash cash equivalents and marketable securities. Our total non-GAAP operating expenses for the first quarter 2021.
$63 $7 million of which RMB SG&A accounted for approximately $33 million and $31 5 million respectively.
Thirdly to revenue, we recorded first quarter 2021 revenue of $7 $6 million, which includes $6 2 million of cosmetic Es and FL net sales and one $4 million and collaboration and other revenue.
We are reiterating our non-GAAP adjusted operating expenses guidance in the range of $235 million to $255 million for the full year 2021, which would support additional clinical development and continued investment in our commercial launches including investment in manufacturing.
Ability to ensure uninterrupted supply of Pittsburgh for commercial patients in our clinical trials.
As a reminder, we are not providing revenue guidance given that our launches continuing their early stages and uncertainty related to the evolving COVID-19 pandemic.
Finally, we remain where things two day with cash and cash equivalents to support our current operating plans into 2023.
Over the past few years, we have deployed multiple strategies to maintain sufficient caveat from important value creating initiatives.
We will continue our prudent expense management and make a new investment with a stage gated approach based on the evolution of our studies and revenue.
We also have a number of options available to us to enhance our cash runway to support our operating plans for growth into the future.
And with net I'd now like to return the call back over to Robert for closing comments Rob.
Thank you Paolo for volume Vicky.
As we emerge from the first quarter, we are encouraged by our positive momentum from we're optimistic that some of the dynamics that have complicated our launches we will start to improve in the second quarter and beyond.
Looking forward, we expect a number of important milestones for the company for the remainder of the year.
We will provide quarterly updates on our progress with the U S has barrick adoption.
We will present updated data with longer follow up on a safety run ins and easy H three O two NFL and easy age 11, a one in prostate cancer at upcoming medical meetings.
We plan to submit our R&D percentage Youtube and eventually initiate the phase one study.
We will initiate the two basket trials in heme malignancies, and solid tumors and finally, we expect to reach alignment with the EMEA on registration path for test there in Europe.
Above all.
We remain optimistic for the long term potential of Tesla, Eric to change the lives of patients living with cancer.
Operator, we'll now open the line for questions.
As a reminder to ask a question you will need to press star one on your telephone.
To withdraw your question press the pound key.
Our first question comes from Michael Yee with Jefferies. Your line is open.
Hi, Rob good morning, and thanks for the update that was very helpful.
We had on two questions.
First was just on the commentary about the I guess.
Precision offish or patient visit environment getting better in March being much better can you maybe just.
Talk to how you think that will lead to perhaps accelerated sales do you have confidence in accelerating sales or do you think it's sort of a general trend of increasing <unk> incremental growth quarter over quarter, maybe just talk to that as you think about the sales trajectory in 2021 and.
Then second question is on the R. Squared study may be fresher Folly I thought there were two interesting things one was the comment about a futility or ICB efficacy analysis at 65% event for us that the first efficacy and then make a comment on the 600 vs 800, because I think thats very interesting and new and is there a chance you would actually have to use.
600, thank you.
Certainly so Mike let me start I'll ask answer your first question around just how we see the year unfolding with regards to the COVID-19 dynamics that we've talked about as I said on the call. We were encouraged to see that.
First quarter, we continued to grow the number of accounts prescribing tests here and we continue to grow debt.
We use the number of bottles, we saw our commercial adoption of 31%, which was actually up quarter on quarter compared to Q4.
If you just go back to the two things that we said that have had the most significant impact on our ability to launch this drug and remember we've launched an entirely virtually from the beginning the two things that have made the most difference had been our ability to get some physicians face to face and access them and have conversations about the data have conversations about the label that's just always more in.
When you have to do it virtually so we're encouraged that with two things happening us putting the reps back out on the field now, allowing them to travel when they are vaccinated and comfortable doing so and the majority of our revpar impact from the field.
It is going to allow for.
More substantial access a more substantial interactions from conditions around the label and the data. The second is always been the fact that patients just aren't they're seeing their physicians. We've seen that this has been down visits had been down as well as new patient starts have been down since the beginning.
First quarter was no different in the fourth quarter. So we're encouraged to see that that's starting to change we're starting to see patients come back in the office for starting to see physicians bring their patients back and obviously for a new drug that just launched you can't get adoption, if the patients out there and the physicians aren't making switch decisions and as we know they typically don't change patient's therapy.
They're not in the office. If you are just seeing them remote. So we're encouraged about both of those things being the leading indicators.
Seeing adoption continue to grow over the course of the year. So has it been the tumors substantial barriers that being said, it's not the same nationally I think like.
We saw with things closing down is happening regionally you see pockets of where some areas are opening more quickly than others.
Some areas have better access where we are able to go back into the customers' offices already and then there are other superbaby close for a bit longer so it's not.
For them across the country, but again, we're encouraged that we're starting to see that happen already.
Sooner than we had anticipated we thought by midyear, we'd really start to see that start to open up and change and Fortunately based on the availability of vaccines.
That started to happen even sooner. So that's why we encourage that because those are the two things that really are most going to help drive the adoption of Tesla Eric in both of those are directly influenced by how quickly those changes happen with respect to our access in patients getting on to see their physicians.
And I'll turn it over to tissue probably to answer your question around 300 to Mike.
Good morning, Mike. This is finally here. So I think just to answer your first question about the income as you recall the randomized study for the phase III has two interims the force.
First interim is based on objective responses that are strictly for futility. So that's just giving you a trend of how you know the studies going it does give you a signal, but it's not for efficacy the London meeting Cynthia line with FDA is about the second interim which is based on PFS events and you are absolutely right at 65% of PFS event. This <unk>.
As an opportunity to actually stop the study early on and you don't have to do all the PFS events. So you know you could have the D debate ability to as long as you have met the predefined events of the study. So it's a it's an important alignment that we had with FDA for the tier two study.
Gosh to your second question about the Dallas. So you know as you recall, we actually had a line with empty on the study.
Design at the time of day approval for the 50 day. Then however, we did complete the 50 done and very quickly without any D N T.
In order to well characterize the combination.
Combination of cosmetic with ice clear even on the agency assets to enroll additional 15 minimum 15 patients at 608 hundred milligrams.
Is not a safety issue. This is basically to get more D day in terms of PK in terms of all the other characteristics, including P. D B.
The safety profile that we observed in the study was consistent with both the package insert. It wasn't there was no additional safety concerns we saw and you know and this is very similar.
Basically with other sponsors or other products that are being combined the dice credit. So the goal is to be able to to enroll these patients on as I mentioned in my in my script that we basically.
<unk> nearly completed a day enrollment for these 15 patients and we are looking for what we're doing everything we can to do the startup activities for the phase III duo minimize any impact on the phase three and hope to be able to enroll that study quickly.
Thank you guys.
Thank you. Our next question comes from Mohit Bansal with Citigroup. Your line is open.
Thanks for taking my question on very good morning.
Just one question from my side, one on clinical side for Chipotle.
So this.
He is asking for.
Exploring 600 milligram B I D.
Is it something to do with USDA is looking for on a back end dose optimization, we saw that with Amgen does.
Something related to tax given that you did not see any significant on me.
In terms of covenants on the application.
Hi, Good morning, I think it does mainly as you said rightly very consistent with what other people are doing the goal is to ensure that there is a you know when we combined the ask where that has no impact on the ask their backbone and I think it's mainly those optimization, it's not a safety signal as I mentioned, we didn't see any day and teams have been able to go into high.
<unk> was up 800 made bad debt task without any DMT. So I think the idea is to be able to look at two doses, which are you know 600 anytime day minimum of 15 patients and do those optimization not a safety signal.
Got it very helpful and the other question is related to.
In response to prior question, you kind of mentioned debt.
Things start opening up a little bit bad debt.
Just trying to understand.
Is it better than your expectations going into the year in terms of how physicians are coming back to the offices.
And how.
Housing start tightening up and then the second part of this question is.
Can you comment on.
The user to test.
Is it.
Is it for the strictly on the users on me two mutations patients on.
If you could provide any metrics on how many how much on.
Would you say is in English.
Deviation return such as body type patients. Thank you.
Sure no.
I'll start this is Robert I'll ask Vickie to add on if theres anything that I missed.
First of all with regards to our view on how things will progress this year and my comment was specifically on the timing of how early this is starting I.
I think just for to be conservative, we'd assume debt, we'd really start to see.
A mass amount of immunizations, and therefore things starting to return to normal around middle of the year, and then slowly progressing and improving over the second half of the year. So it's encouraging to see that things are starting to open back up as you see many states have removed their restrictions around COVID-19, whether that's a good thing or a bad thing youre seeing a lot of states that are now doing that lifting there.
Our restrictions.
I think in terms of how that progresses.
I don't want to give guidance on it because it's happening in pockets as I said you have some accounts that are opened already some that have not.
When we talk to physicians about patients coming back in many of them save for their offices are very busy again.
Some of them say that they have had patients not come back in because they didn't want to put them at risk that others have said, it's the patients who actually canceled because they didn't want to be at risk. So I think theres a lot of things at play here.
Obviously with things like that.
On the J&J vaccine being pulled for a period of time that affected the supply chain of vaccine dose for kinds of things that we can never anticipate so ive tried not to be too specific on.
However, thinking about the year other than the fact that it seems to be starting sooner than we thought.
There seems to be a real desire to go back to doing things more normally we said I think 57 per script in the pre recorded remarks debt.
We're starting to see even regional medical conferences go back to face to face because they desire to hear from industry. They want to be educated they wouldn't know about new drugs that are coming out and so some of the regional medical conferences are also starting to go back to being.
Face to face meetings as opposed to virtual so those are the things that encourage us into other things that we think are most going to be.
Useful to the increased adoption to test there because those things return to normal.
With regards to testing I'll start and Vicki can add to it but the testing as you asked this a barrier for us.
Tests, Derik and I think one of the things that we've observed in our research is the testing is an alpha even done as a part of the decision whether to use has bearing on in fact about half of for patients who are tested are tested in the frontline of diagnosis before theyre, even treat it. So some of that is for prognostic reasons. Some of it is against this just just wanted to understand the type of Follicular lymphoma.
The other patient passed so that accounts for almost half of the testing.
The other half from testing is coming in patients who have relapsed refractory disease or.
Our research says, it's not because they're they're looking to use it to determine whether or not to use has barrick theyre just trying to better characterize the type of patient and perhaps debt treatment expectations for patients who are on <unk>, but I think it's.
The use of the test is actually being done for a number of different reasons across different lines of therapy and picky I'll ask if you want to comment further on that yeah.
Yeah, I think the only other point I would add as you now are seeing testing increase. This is the first time really in Follicular lymphoma that these physicians have had an opportunity to really understand this particular mutation on the disease and so theres a lot of interest.
We've done a lot of focus groups on a physician is consistently say you know I just want to know what the status is for the patient I mean, not necessarily use that information to make a treatment decision.
But it certainly is helpful for setting expectations, if I'm going to treat them attached Eric.
On other things, where we want to make sure that physicians have access to other testing if they choose to do so and while on the next gen sequencing panels are available for most physicians. There are group I mentioned that about 25%, let's say you know on I, just don't want to run a full panel when I only need one.
Non.
Th two mutation results so well some of the institution is a handful that have COBOL testing available.
Which is the PCR test, we're looking at opportunities to bring an innovative solution for these physicians granted we just want to meet their needs.
And make sure that there's not any significant reason for them not true prescribed <unk> and make sure that we're bringing every solution possible for them.
Got it.
Some things soon in the near future.
Got it really really helpful. Thank you Robert making video for Citi.
Thanks Mohit.
Yes.
Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.
Thanks, Thanks for the update and good morning.
Adjusted EBITDA.
Just.
<unk> Melissa is that getting better are you seeing that kind of similar trend for.
For scripts for revenues.
Any color around April would be great.
Well I think our commentary is not so much on scripts on revenues.
It's probably too early to comment on that Peter but I think it's on things that we see that are happening in the market that we've always thought of being very positive leading indicators to our ability to continue to drive adoption of test Eric and that is again, our ability to access the customer.
And our ability and the ability for patients to get back in and see their physicians and to see that trend that we've seen pretty consistently on new prescriptions that have been trending down 20% to 40% depending on the line of therapy.
Actually start to write itself those are both very important to achieving adoption of any new product, but Tesla Eric in particular since we launched just in the middle of the pandemic last year. So those are the things that give us optimism that this is going to bode well for our ability to access the customer, but also their ability to see their patients and start to change the.
And patients who need to change and many of these patients keep in mind they've been away for some time.
Not on all offices, but there are patients who have been away from their office for many many months now and so I think it's going to be imperative for just for physicians to get those patients back in.
As they can because many of them are likely either because of they've dropped off on treatment. They progressed.
It will be important that they're able to get them back in and make that treatment change.
Got you. Thank you and then the basket study for <unk>.
I guess the expansion for Tazemetostat.
Indications could read out first.
Yeah. So hi, Peter this is a poly for the balance of the study is.
Innovative design, that's basically on looking at the safety data and then you're looking at all the indications together. So it's basically all the different cohorts for different indications starting with the heme basket study the indications that we're looking at the credit the lymphoma, DLD, Seattle multiple myeloma and mantle cell the goal it would be able to actually look at on the.
Cohorts together because it's open label you can enroll patients in each cohort and look on look at the cohort on itself. So you don't have to really see which one is for us because they could they would be enrolling simultaneously and then you know we are using a basal metabolic by looking at total number of patients on understanding what the biomarker data.
Alright population holiday bidding in terms of efficacy and we'll be able to eat that day that out regularly starting from 2022. So that's the goals both for heme and solid basket studies.
Good day. Thank you. Thank you switch it back into the queue.
Okay.
Thanks Peter.
Thank you. Our next question comes from Joe Thome with Cowen and company. Your line is open.
Hi, there. Thank you for taking my questions and good morning, everyone.
The dose optimization questions just to follow up on the basket trial in the heme malignancies. If you do see a signal in one of these combination baskets do you anticipate there's going to be sort of substantial additional dose finding work with the combination.
Like you said to sort of optimize that.
Efficacy of both aspects there and then in the study to initial study.
It's going to be a monotherapy study or is this also going to be in combination and how are you thinking about the necessary dose in those two settings. Thank you.
Yeah. Thank you <unk>, let me start with the heme basket studies. So I think just to reflect on the dose optimization I just wanted to kind of clarify that we have studied more than pas on patient at 800 milligrams sellers on the optimized for delivery in the monotherapy study of course, you look at the combination of his study the two of those together so the <unk>.
We'll have to be able to do the 50 dundon with these combinations early on and then be able to do a dose escalation cannabis.
Just on the data on based on high School combination studies that we have done like R. Chop being blamed the doxorubicin you know me.
<unk> showed that with a checkpoint inhibitor the different combination that we have done so far they've been showed that the income line at the highest was up 800 milligrams. They showed that the das credit as well. So I think the goal would be able to dose escalate in this combination and the heme basket study and once we know that we can see the signal expand that to defend and multiple cohorts as they.
I mentioned in terms of different indications.
In terms of <unk>. The first in human study you know as you know the first in human studies any to optimize the dose from the beginning to understand the RMT D. Our maximum application until it. So the goal would be able to escalate and monoterpene, because we have to find the dose plus in monotherapy and then expand particularly for 2014 and division called assured.
That you know there's great data pre clinically that we believe that it may be really effective and people protein, which is a big unmet need in multiple myeloma. So we would expand on the T for <unk> multiple myeloma and also study.
The non people 14, as well as CIBC on as monotherapy once they have information about the signal in monotherapy, we absolutely will look at different combinations and in those indications on them anymore. So I think as I said, we have a big lifecycle plan not only to those optimize both for Cadbury as well as per said day too, but also have a <unk>.
Late lifecycle of pad I think overall I want to say that based on the day W. Have so far we feel comfortable debt 800 milligram debt matures in a safety than it is the optimized dose but of course, they look at the combination of let's say.
Perfect. Thanks, so much.
Thank you. Our next question comes from David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking my question.
Hey, David.
Hello, specifically with respect to vaccinations.
How is the dynamic with.
Ah patients.
Getting multiple myeloma patients are getting vaccinated is there a resistance within the population itself.
And how do you see that dynamic going forward.
Yes, it's a great question, David I'll turn that over to Sabawi, because she's been interacting with physicians about this both from a commercial point of view, but also from the standpoint of interaction in our clinical trials, so I'll turn that over to <unk> to answer.
Yes, good morning, David side, it's a very interesting question you know I believe you were paying debt all patients are all especially on any patient file for lymphoma as well as other multiple myeloma heme malignancies fluid to be able to get back to Nathan I would want to get back the nation I think what I'm hearing from physicians as the majority, but not all because there is a concern about the immune therapies as well.
The Italian on some of them are having a getting a touch on lab and as you know other concern is about having antibodies or they have to stop the drug for glad you have to ensure that you have antibodies that though with the vaccine. So like we are heading is that there's a there's an increase but not all patients that actually getting vaccinated because of the five for them. They don't want.
Stop that's happy they wanted to continue on the therapy. So I think it may change in future and eventually patients may be comfortable I think it's more in in like less interest in diseases and positive going on but if you look at microphone line Omar Bcl debt very aggressive, but they don't want to stop that happening, especially the ones that they have to stop to get the vaccination. So I.
I think it's it makes me think it through debt or how it changes.
How long do you think I guess for <unk> you could take on this dynamic shifts.
I think it's hard to comment you know as people get comfortable about the logged on data with vaccination in that channel even if they stop the medication for a couple of things like the Tulsa lab, it's still okay. I think if it becomes better it's hard to comment on now, but I've seen that as a doctor physician they feel that it is increasing and gradually.
We see that improvement this year and again something else yes.
Doctors, given some sort of vision or estimate on how many patients.
Had that level of resistance.
Yeah, it's very anecdotal because I've talked to the position of aspirations, but what this is.
I would say majority on the patients want to get vaccinated, but some subset they want it's like they they don't tend to give the quantification number they just kind of give like anecdotally, but as you know it all depends on individual patient, whether they want us to stop canopy or not and take the vaccination, but I'm, hoping as a person myself that eventually this will get better.
And people will start thinking vaccination.
Thanks for taking my questions, but we havent seen David.
Just to follow up on that David maybe you should comment on this as well, but even so for example in the 302 study.
Where are we left enrollment open because we were in discussions with the agency about potential ways that we could finish the dose optimization work, but there has been a great interest in enrolling positioned Rowan enrolling patients in the 302 study and as we left it open Chipotle mentioned, we're nearly complete with even the additional patients that the FDA wanted to see is a part of that dose optimization. So.
We've not seen that had a significant impact on the ability to enroll three or two for example, so to your point about many patients are being vaccinated physicians for more comfortable with treating these patients.
That is what we're seeing in terms of how it's impacting 302, which would be really relevant and should probably be you want to comment further on that.
Absolutely I think we are seeing a lot of enthusiasm in the Asquith study with Dr. Study I think Oh My God. If your question is whether the physician will come that other patients that have come back and take the kind of be absolutely I think it will be gradual change and people are cycling that he is seeing no impact on the tier two study actually we had patients who like Rob said.
For the safety done it even before.
<unk> asked us for.
For the numbers. So I think we have seen debt interest in patients are coming for that therapy is effective vaccination on us.
Excellent. Thank you very much for that.
Thank you. Our next question comes from Andrew Burns with assets SBB Leerink. Your line is open.
Hi, Thanks.
Couple of questions on testing Hi, Rob a couple of questions on testing on a follow up on <unk> questions and then one on the pipe.
How long is it taking to get patients tested.
Or is that actually being done when conditions warrant a sequence for patient with on <unk> status, what's the bottleneck.
You alluded to in the prepared comments and then you said in the Q&A session. A fair number of patients are now being treated in the frontline for easy H two.
When did that actually start happening.
When do you think those patients will be presenting would be candidates for <unk>.
And then on.
Also I know you said you have limited visibility on.
Wild type vs mutant patients are getting pads America because of the channels, but I thought usually that gives you better access for that type of information. So just trying to get a sense of.
What percentage of patients that are actually getting the drug a wild type vs mutant.
Absolutely.
The other question on the interim analysis, if I can do that on our cluster.
To answer those questions why don't we.
We address the questions on testing first and I'll.
Let's go through them on that one and then I'll ask you to comment as well if I Miss anything but your first one was how they're doing how are they doing it now on what's the bottleneck for the 25 or seven percentage that you spoke about.
They are actually a number of ways that they can test many institutions have their own test. So if a physician is an academic physicians many of those are using their institutions panel.
There are other panels available day or commercial panels quest diagnostic panel. There is a foundation medicine, all that have <unk> on them.
And so there are many different ways physicians can choose to test patients for <unk>.
I think what Vicki had indicated his community physician youre not in a in an institution you don't have access to the institutional panel.
Those commercial panels have many many tests on them and so what they really are desiring a test that actually just specific for <unk>. So that you don't have to do that complete panel.
They do have access to panels today is just not ideal and so one of the things. We're looking for is to see if we can make things simpler for that group of physicians, who choose one adjusted is specific for easy H, two but I wouldn't say, it's a it's a bottleneck for.
Getting tested or bottleneck, even for patients going on tests there.
That's not always the reason that they're looking to test patients.
I think your other question was how how quickly when did we start seeing testing in the first line.
And I just want to restate, what you said or make sure I heard you right.
Starting to see used in the first line I didn't comment on making on seeing <unk> used in the first line patients are tested there.
<unk> is one of the part of the flip the severity index and so there is a reason that physicians will be testing in the newly diagnosed patients for front line.
Because it is a part of that and they are testing as a part of their severity score but it also is just because now you said its when do you test. It's one new piece of information about the disease that wasn't relevant or wasn't well known before.
We bought <unk> to market and now its one more piece of information that can obtain around the disease.
Vicki anything else you'd add to those two things no you covered it well yes, okay.
Could I just I didn't mean, the patient is being tested on the frontline it'd just be treated in the front line I'm just curious.
When they started being tested and obviously there is a period, where they will be responding to that.
And the second line treatment for wet when do you think you'll start seeing patients with known easy H two status being candidates for Tesla Eric.
Well, it's a great point.
And so I think we've seen testing in the front line.
For some time and then some physician that's starting to grow because again, it's a part of the slippage severity index. So it's been tested for some time as long as it's been a part of that panel.
But I would say growing in terms of wind and we're encouraged that we're seeing more frontline testing because it means that when the patient relapse because our label allows for use of cash Barrick as early as the second line.
It's good that they could already noted the ESG mutational status, particularly since in the second line with other combinations that have full approvals like R squared and Bendamustine rituximab for.
Particularly for <unk> mutation patients as a monotherapy, we think that test there could be very attractive in the second line setting.
And so that's a that's a good thing it's just continued to grow but it didn't just start because he can just how to choose from a prognostic point of view.
And in terms of how long you would expect I mean patients in the frontline setting.
Often they go for many months before they relapse and then you have 24 patients which are the ones who tend to progress within the first 24 months. So theres a pretty wide variety of how quickly those patients progress from frontline for second line.
Depending on the response to their initial treatment.
And your other okay.
Was about Eaton vs Wild type.
I'm happy to answer that so what we've seen as I mentioned amongst us the.
Nominate use right now for test for Eric is in the third line plus setting as long as we are still seeing used in second line as well.
And when we look at the split vs. Wild type, we actually don't get that data from the claims data because it's the diagnostic piece right isn't in the claim the claims for the drug. So what we have to do is we do pretty extensive market research with providers that are prescribing and what we're seeing from that research is that we.
We are seeing more on mute.
Utilization in both the second line on the third line plus setting vs Wild type.
Does that answer line.
But I think for more okay.
That would be good andi think we'd always assume debt as a monotherapy that we would see a higher share in the mutant population. So that's entirely consistent with what we would've expected and then the other group that Vicki as Rick mentioned, which is on tested which is we actually don't know their status because the physician didnt feel the need to test the policies don't required to test.
So would you say debt of the patients that are getting because Eric because it is at 75 per cent are easier to see positive or is it a number less from us.
I think it's hard to say, Andy because they've been tested patients and you don't it's difficult to know for those which they are.
Okay.
That does.
Moving the claims data for great.
Right.
Okay and then just a question on the second interim analysis for the R. Squared trial is that going to be an easy it's true wild type for mutant patients and how should we expect the control arm to perform just trying to get a sense for how high the bar is for Tesla Eric for the R Squared Regiment.
Yeah, No. That's a great question on is there for.
Chipotle so the way we have the income is actually to ensure we have the success on the study. So we are doing a hierarchical testing so that there's a value for the alpha spend so we are starting with easiest to mute and once that is positive then moving on to what else population. So the goal is to be able to test for the easiest commute and then what are popular.
The study is publicly this generic to ensure that we have enough bartlett and events that weekend.
Wanted to we can look at these guests on mute on its own on overall population both of them. So that is the goal looking at the income income and in terms of the the hull will the debt.
The experimental on behavior. So it's a little different that's why we did the adaptive design and I think because we know that the augment study only indoors.
For most sensitive patients because that's what their competitor on the odd enrolling just touched on lab refractory patient population.
Because you know that's the real was about 30% of the patients. So you know.
We are going to see.
Debt adaptive be they in the interim how the competitor on is behaving when he'd anecdotally from the physicians had believed that they'd behave less because those patients are in a nod that responsive to treatment, especially for the R. Square. So we will as we look at the study as well because they didn't really have an opportunity to look at how this how this expand Mcdonald a day.
Compared to the test the fast quick and another important component that's different than the augment study is also that we have maintenance on them and we believe that that will benefit the overall PFS because the PFS is not up there.
Tasked with US clip on here is actually on the maintenance of cash and the maintenance arm of placebo. So it's a very innovative design you have an opportunity to look at all these things other than the interval and be able to assess an adaptive trial accordingly.
Okay. Thanks for letting me hog on the balance I appreciate your answers for that certainly.
Okay.
Thank you and I'm showing no other questions in the queue I'd like to turn the call back to Rob based Moore for any closing remarks.
Okay. Thank you operator, and thank you all for joining US today. Thanks for all the questions. We hope that you all stay safe and healthy and have a great day take care everyone.
This concludes today's conference call. Thank you for participating you may now disconnect.
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