Good morning everyone. My name is Seth, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Blueprint Medicines Second Quarter 2021 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise.

After the speakers' remarks, there will be a question-and-answer session. .

Thank you, operator. Good morning everyone, and welcome to Blueprint Medicines Second Quarter 2021 Financial and Operating Results Conference Call. This morning, we issued a press release, which outlines the topics we plan to discuss today.

You can access the press release, as well as the slides that we'll be reviewing today, by going to the Investors section of our website at www.blueprintmedicines.com.

Today on our call, Jeff Albers, our Chief Executive Officer will discuss Blueprint Medicines' Second Quarter 2021 business highlights; Christy Rossi, our Chief Commercial Officer will provide a commercial update; Becker Hewes, Chief Medical Officer will review our recent clinical progress; and Mike Landsittel, our Chief Financial Officer will review our second quarter 2021 financial results.

Before we get started, I would like to remind everyone that statements we make on this conference call will include forward-looking statements.

Actual events or results could differ materially from those expressed or implied by any forward-looking statements, as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our SEC filings.

In addition, any forward-looking statement made on this call, represents our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. Now, here's our CEO, Jeff Albers. .

Thanks, Kristin and good morning everyone. Thanks for joining us today, to review our second quarter performance. The progress made across our portfolio in the second quarter puts us in the strongest position we've ever been in as a company.

In January, we laid out our strategic priorities for 2021, which were, one, to accelerate the global adoption of AYVAKIT and GAVRETO; two, to advance the next wave of therapeutic candidates into the clinic; and three, to further expand our precision therapy research pipeline.

Underlying these three pillars is a single ambition, to build the world's leading precision medicine company and make real the promise of precision therapy to improve the lives of people with cancer and hematologic disorders. In June, we received US FDA approval of AYVAKIT for the treatment of advanced systemic mastocytosis or SM.

This was a significant achievement for Blueprint and the culmination of nearly a decade of hard work from our team and partnership with the medical and patient communities..

identifying patients, providing disease and product education, and ensuring best-in-class support..

Thank you, Christy, and good morning, everyone. Let's start with the PIONEER trial of AYVAKIT in non-advanced disease. As we celebrate Davis approval for advanced SM, we're eager to expand our impact to non-advanced disease, which comprises the overwhelming majority of patients..

Thanks, Becker. Earlier this morning we reported detailed second quarter financial results in our press release. And for today's call I'll just touch on a few highlights from the quarter.

Total revenues for the quarter were $27.3 million, highlighting our growing diversity of global revenue -- our global revenue base and positioning us for strong future growth. This included $11.4 million in net product revenues, as Christy discussed and $15.9 million in collaboration revenue.

Collaboration revenue was primarily driven by commercial supply shipments to our partners CStone and Roche to support our broadening geographic approvals. Collaboration revenue also included royalty revenue for sales of AYVAKIT and GAVRETO by CStone in Greater China.

Our total costs and operating expenses in the second quarter increased moderately compared to the first quarter of 2021. We saw an increase in cost of sales related to drug product shipments to our partners. In addition, SG&A expenses increased driven by our commercial infrastructure expansion.

As we increase investment in our promising early-stage programs over the next few quarters and expand our commercial efforts with the launch of AYVAKIT in advanced SM, we expect to see continued increases in future quarter-over-quarter R&D and SG&A operating expenses.

We ended the second quarter with nearly $1.4 billion in cash on hand ensuring that we have sufficient resources to invest in our growing pipeline of wholly-owned drug candidates.

Overall, with the recent approval of AYVAKIT and advanced SM, strong collaboration execution and a deepening pipeline, we have a solid foundation from which to drive future revenue growth.

Anchored by sales of AYVAKIT and the potential for several meaningful collaboration milestones, we anticipate that our second half revenue will more than double over the first half, which positions us to meet our 2021 revenue guidance of $150 million for the full year.

This second half financial momentum will then set us up for a series of important clinical catalysts in 2022, as we continue to build the world's leading precision medicine company.

So with that, I'd now like to turn the call over to the operator for questions, Operator?.

Question-and:.

Thank you. Our first question comes from the line of Salveen Richter from Goldman Sachs. Please go ahead..

Good morning. Congratulations on the launch.

What are your thoughts here on the trajectory of the advanced SM launch? Is there an initial bolus given the demand you mentioned? And then, at the 70 hematological centers what is the overlap there with the non-advanced SM total opportunity? And then, separately, if you could just comment on the accounting mechanics for next quarter when Roche takes over booking GAVRETO sales? Thank you..

Great, I can start. This is Christy and then I'll let Mike chime in on the accounting. So we've been really excited to see the initial feedback and interest we're seeing around the advanced SM launch.

I think what -- the thing that is particularly notable has been that, yeah, we're seeing interest certainly among those 72 centers, but also seeing a lot of organic interest in the community setting, which I think is a really good indicator of the potential for future growth.

It's early, obviously, so understanding exactly the dynamics around bolus versus not, et cetera.

I think we'll have more clarity on that as we emerge over time, but I'm excited about the potential for ongoing growth here, given that we are seeing broad interest and in my experience, the breadth of interest and breadth of prescribing is often really a key driver of ongoing demand growth over done.

We're also seeing utilization amongst patients that look like they're -- they've been previously diagnosed and treated, but also some uptake amongst patients with no indicators at least of another advanced SM therapy in their history, which suggest that we're seeing prevalent patients, but potentially some newly diagnosed patients coming on to therapy over time.

So we look forward to seeing how that continues to emerge as we go forward from here. The overlap amongst the centers, I mean the 70 centers are critical for treatment of advanced SM patients. Certainly, as we get into the non-advanced setting, we will be broadening out in TV allergy setting to a greater extent.

But those centers are going to be critical for both indications. As I said before, SM is very much one disease with a common driver, e-comm and mutation and hematology can play a critical role in the diagnosis of non-advanced patients as well.

So certainly getting established with advanced disease in these centers is going to be a critical part of setting us up for the non-advanced indication that we expect to receive over time. Maybe I'll let Mike comment on the accounting. .

Yes. So for the accounting, just as a reminder, in Q2 we recognized end-user sales of GAVRETO's product revenue and then there was a true-up to the profit sharing for the U.S. that flowed through SG&A. Starting in Q3, as Christy mentioned, Roche will be booking end-user sales under the collaboration.

And what we'll do is, we'll record our share of the collaboration profit or loss as one line item on our income statement. It will either show up in the revenue section, if the collaboration is profitable or in the expenses, if the collaboration is going to loss position.

We're also intending to continue to provide transparency in our global product sales at the end user level going forward..

Thank you..

Our next question comes from the line of Marc Frahm from Cowen. Please go ahead..

Hi. Thanks for taking my questions. One on -- to start with on AYVAKIT.

Just, was there any stocking impact from the launch of the new dose strength in the quarter, or is it kind of all demand?.

Yes. So, very minimal. We -- the advanced SM dose, as you know, starting dose is 200 and we already had 300, 200, 100-milligram dose in the channel. So there's minimal 25 and 50 in the channel, obviously, to be available.

Patients need it as part of their ongoing treatment, but we haven't seen a lot of utilization of those strengths and that wasn't a huge driver of what we saw in Q2..

Okay. Thanks. That's helpful. And then, maybe looking to the pipeline. Just for RET, you were able to kind of report initial data about a year after initiating the trial.

Do you think that's still a reasonable expectation for 945 monotherapy data, or do you think we should maybe expect you to wait a little bit longer for maybe combo data to kind of mature before you start reporting data out of the EGFR program?.

So, as we do every year, at the beginning of 2022, we'll lay out guidance in terms of sharing data and expectations, more specifically around timing. What -- as Becker highlighted, we think we're really well positioned now with this wave of new programs having either recently entered a clinic or soon entered the clinic.

And so, to me, the company fundamentally feels different now than it did, say, a year ago, getting the breadth of development candidates that we got had pulled through and the quality of those candidates, late last year early this year.

This advanced SM approval in the early indications, as Christy highlighted, that we're seeing in terms of uptake and giving us a better sense of the magnitude of that opportunity. I thought, Mike said it well with the -- we'll ride the launch into next year, but then we're looking to sort of lay out a series of clinical updates across these programs.

So I don't think we're at the point where we'll specifically guide to any one of those, but the breadth of those launches or of those clinical trials is what, for me, is really exciting..

Okay. Thank you..

Our next question is from Dane Leone from Raymond James. Please go ahead..

Hi. Thank you for taking the questions and congratulations on all the updates and launch in ASM. Just one question for me, following up on the EGFR question Mark asked.

Could you just maybe elaborate a little bit more in terms of the clinical strategy here? What you need to see out of the Phase 1 to then move into combination studies, which I think a lot of us think is the end game here? And again, as much as I can push you to give some idea of time lines on that effort. It would be appreciated. Thank you..

Yes. First factor, I'll take that. With respect to the overall strategy, you hit the nail head. The combinations are the key to providing those benefit with these compounds to patients. We are going to explore, as I said, single agent activity of both, and we will start combinations before we finish exploring single-agent activity.

Combinations, both with BLU-945 and 701 together, and then with each of those with other third generation type kinase inhibitors for EGFR mutant lung cancer. So, I think what you'll see there's a number of different experiments going on simultaneously in different patient populations.

We're also learning more about the mutation profile of the patients, how they present either alone or in combinations that is mutating. And so, we'll refine our strategy as we understand the biology more and the -- our ability to combine these compounds during the trial.

With respect to timing, as we've previously reported, we started the 945 dose escalation recently, and we expect to enter BLU-701 by the end of this year.

And the extent to which the -- as Jeff said, rather than releasing data piece meal, we have so much data coming out next year that there will be periodic update I hesitate to speculate or give about any specific thing individually..

This is Jeff. Maybe just combining the comments from Mark and Dane and comparing them to RET.

All of us when you're looking -- think about forward-looking statements are speculated, when we'll have data, how quickly you'll move through the dose escalation to get to an effective dose, as Becker just highlighted, understanding the biology and where there's likely to be the greatest benefit. Early signs are encouraging on this end.

The fact that with the first couple of sites activated we're already seeing, patients lined up with some of those sites patients willing to travel. So, the first marker is, are the patients there can you identify them and we're moving through that nicely. And then, for 701, as Becker said, we're looking to move into the clinic by the end of this year.

The enthusiasm from investigators and potential investigators there to get that up and running, is just one more of those markers. And so, tied together is why I think, we're collectively so optimistic about those two programs together..

Great. Thank you, guys. Congratulations on all the updates..

The next question comes from Reni Benjamin from JMP Securities. Please go ahead..

Hi. Good morning, guys. Thanks for taking the questions and congratulations as well.

Just one question on GAVRETO, regarding -- can you just give us a status update of what's happening with the application there? And kind of importantly, what's the rest of the world filing strategy for 2021 in terms of other geographies to look at? And just as a follow-up, I know Chris you talked about patient identification.

And I thought in the past we talked about digital PCR, NGS, and then your own sort of task I think, CStone is coming up with our own test as well. Can you just give us an update as to what's happening with your own testing product? Thanks..

Let Becker you take the first part of that with Roche's efforts outside the US, and then Christy, you talked a little bit about patient identification..

Yes. So, as you'll remember this GAVRETO outside the US is owned by Roche and they're at least in the filing, we've guided to having filed that and that's well under review right now. With respect to the strategy in other regions, they have a number of other regions lined up to shortly follow the European evaluation of EDASA..

And then, I can pick up the thread on patient identification and run. I think you might have been asking around advanced them, but let me know if I'm picking in a different direction than what you were..

I thought it was GAVRETO..

Are you asking about GAVRETO or... .

No. No, advanced SM, sorry. Yes. So first time..

Okay. So, yes, so the most important -- one of the most important patient ID levers across advanced and non-advanced disease, frankly, is for TAB in advanced disease, where I would say that becomes most important is in SMA where you're really trying to identify the FM component.

But clearly most advanced patients are diagnosed with something in non-advanced disease driving accessibility to highly sensitive blood-based testing is really critical. And there, I think we've made a lot of progress. So, the goal is it's not so much our own assay.

What we're trying to do is really enable capability among lab broadly in markets that we're going to be commercializing in, to have that available so that physicians and patients can access testing easily.

Over the last six to nine months, I would say, there's been good progress in terms of the number of commercially available highly sensitive test in the United States.

And then we are working as well with a few large lab partners to further develop that capability and make sure that it's accessible and available to patients and I'm expecting ongoing progress against that even as we go through the remainder of this year.

So I would say, generally speaking, we're in a much better spot even now than we were 12 months ago and would expect to see ongoing developments there from here..

Great. Thanks for taking the questions and congrats..

The next question is from Peter Lawson at Barclays. Please go ahead..

Hi. Thanks for taking the question. Thanks for the update.

Just on the preclinical update for 945 and 701, just if you kind of perhaps walk through what we should expect to see and the potential venue for that in the second half?.

So I assume what you're talking about is the combination of 701 and 945 in preclinical models. We haven't decided on a specific venue, but we are working on generating that data, identifying the proper models and animal models for these complex mutation profile is where we've gone. We are partnering in. We have internal models.

So you should just look forward later this year for a couple of different looks at that..

Got you. Thanks so much..

The next question is from David Lebowitz from Morgan Stanley. Please go ahead..

Thank you very much for taking my question. In the early run of the AYVAKIT launch in ASM, there's certainly been -- it sounds like there've been a lot of inquiries about patients with ISM that you end up referring to the PIONEER trial.

Are any of the physicians actually trying to take these ISM patients and put them on drug now at this point or certainly inquiring this ways they might be able to get patients on drug as you had elaborated in the past it is overall considered one disease?.

Sure. So the data that we have right now suggests that the patients are being prescribed advanced SM patients as diagnosed by their health care provider. Certainly, as I mentioned anecdotally and that's not the only slide, I will say, where we have seen both advanced and non-advanced patients being treated.

And interest in PIONEER, also potentially interest in HARBOR down the road. So I think it just highlights again the synergy that we're seeing in our engagement with this community. You're right, SM is absolutely one disease, subtyping is complicated. So I think we may see over time utilization.

But I think what we've heard is that early on we expect utilization to be in advance with the patients and we have no data to suggest anything differently from what we're seeing..

Thanks for taking my question..

The next question is from Benjamin Kallo from Baird. Please go ahead..

Hello. This is Benjamin on for Joel Beatty. Just a few questions for us mainly on AYVAKIT. I'm just wondering if there's a sense of the number of repeat scripts potentially in a number of new prescribers. And then I was wondering if you also could comment more on the demand from community physicians.

Is it more demand, or is there interest, or is there maybe specific examples you might be able to point to you to kind of provide a little bit of clarity on that. Thank you so much..

Sure.

So we are, I guess, at this point like five weeks in or so, right? So we are -- most -- I mean, the majority of the demand that I've been commenting on is new patients, where we would certainly expect with an indication like this and given the incredible duration of therapy that we see with AYVAKIT, which is I think one of the ways that it's really transforming care for these patients, we would expect long duration over time.

And so certainly seeing that revenue build as we see refills as well as new patients coming in. But based on where we are in the calendar, we've barely even gotten to the point where you would see your first results starting to come through.

In terms of the community, again, it's early days, but I think the market for us was that we saw interest really almost immediately coming from a broad number of stakeholders. And I would say a significant percent of our utilization already is coming from the community, which I think is a really good indicator.

And we'll likely be sharing more about that as we progress to the launch and continue to build that data. But this is a rare disease. And to me what this suggests is we are often the launch of a transformational therapy catalyzes changes in the treatment paradigm as well.

And so I would not be surprised to see that here and to see via really enabling broader care of advanced assumptions both in centers as well as in community practices. .

Great. Thank you. And then if I could sneak one more quick follow-up.

On the underutilization of the 25-milligram and 50-milligram dose, any thoughts there? Is that kind of surprising, or does that speak more to like your comments earlier about the early in the launch?.

Yes, absolutely.

So it's certainly not being underutilized in terms of what we would expect, right? I mean, our -- the starting dose for advanced SM patients 200 milligrams we expect the majority of patients to be treated at 200 milligrams, maybe 100 milligrams, 2750 are there certainly to enable appropriate dose adjustments to care on an individual basis based on a patient and a provider, but I wouldn't expect to see broad use of those dose strengths in advance SM.

So we're at -- there's nothing that I've seen so far that is different than what we would have expected. .

Got it. Thank you so much..

The next question is from Michael Schmidt at Guggenheim Partners. Please go ahead. .

Hey guys, thanks for taking my question and congrats on the progress as well. I had a couple on your CDK2 inhibitor program.

Just help us understand how your collaboration with MD Anderson actually accelerate the program as you mentioned? And then secondly just mechanistically, how should we think about the 222 activity perhaps in PPNE amplified or cycline amplified cases relative to other potential mechanisms that include for example one inhibition or PKM2 one inhibition in the print setting? Thanks so much..

Thanks Michael. Let me start with MD Anderson. So, I think as everyone knows MD Anderson is really a powerhouse with respect to translational research. Just identifying a selective CDK inhibitor is really just the beginning of the journey.

And you've seen in CDK4/6 development that identifying signals Pampa requires combination sophisticated preclinical models to understand how and when to use these drugs together.

And in this case, we're looking at 46 inhibitors combining two inhibitors and a number of other mechanisms including those that you just mentioned where novel combinations may really uncover amazing therapeutic advantage in different patient populations.

The other place that they have pointed angle on the science is that, there are so many patients that dose with MD Anderson.

So their ability to clear tumor banks and really deeply understand the biology of the indications such as ovarian and breast cancer and endometrial and beyond that we have identified and then calling additional tumors off the shelf to understand where there's a vulnerability that might allow us to either use Blue T2 or a combination that either we or they identify is really unprecedented when you look at the breadth of the tumor banks that they have and the investigators that are involved.

So we expect to enhance our understanding activity where we expect it. And -- but what I'm really excited about is what we don't expect. This was what happened with Pfizer and CDK4/6 where UCLA identified a signal that really transformed breast cancer. And so this collaboration there's one that I'm most excited about my entire career.

With respect to the other modalities, it's really posing to speculate about how the relative activity will compare.

We're looking at cycling amplified cancers expecting that a subset of these malignancies will be so dependent on the CDK2 pathway that we can futon apoptosis when we net the extent to which that achievable in other mechanisms, we're going to have to see.

But as I said, as we go into novel parts of the tumors biology understanding how to combine novel compounds and the more standard of care compound is going to be something that we're really focused on. .

Great. Thank you..

The next question is from Andrew Berens from SVB Leerink. Please go ahead. .

Thanks. A couple of questions for me on RET and then one on ASM. I was wondering if you could give us some color on the RET market as you guys are getting 45% of new patient starts. And I think previously you said it was around 25% in Q1, but we haven't seen that translated to the P&L yet.

Is that because of sampling in the new patients, or is it just not as many new patients as we had anticipated? And then what percentage of diagnosed patients are actually being treated with any RET inhibitor? And are you seeing any frontline usage, or is research predominantly after a. And then just a question on the ASM launch.

Should we expect to see any change in the gross to net adjustments now that you're expanding into a larger opportunity?.

Great. Those are all for me. So I can start with RET. And actually, the questions that you asked are all related. So the way that we think about this market is new patient starts being sort of the first indicator, total patient share then following over time and total patient share.

As total share approaches new share more quickly obviously the factor of the market grows. And so, we know that Lilly had a bit of a time advantage on us in terms of being the only game in town for six months prior to having both indications available.

And so as we've gained new patient share we're seeing our total patient share grow, but it will take time for a total share to catch up to where we see those new starts coming. So it's essentially thinking about like NRx versus TRx and it's an indicator of revenue growth. And I think we've seen that.

I mean we're continuing to see really robust revenue growth relative to what we've seen from certainly for Tableau over the last period of time. I think we would like to see the market growing more and growing faster to your point. And I think that's really where we're spending a lot of time focusing with Genentech.

Our best estimate right now is that maybe 20%, maybe a little bit more than that of potential RET patients are being diagnosed and then treated with a selective RET inhibitor. And so there's certainly a lot of opportunity and we think to continue to really grow patient ID and that the rebound post-COVID is happening in terms of testing et cetera.

So we're excited to see that pull-through. And we're seeing use across lines of therapy. Right now, but certainly there's an opportunity to get to patients earlier upon diagnosis. And so that's something that again we're focused on. From a perspective, I wouldn't expect dramatic changes from where we were with AYVAKIT.

Certainly, the strategy that we've been using to distribute the product in the United States is consistent and our broad access strategy is consistent there. So I would not expect dramatic changes as against system..

Okay. Thanks. Appreciate it..

Our next question comes from Arlinda Lee at Canaccord. Please go ahead..

Great. Thanks for taking my question. I was interested in the overlap of -- in ISM versus ASM. You mentioned, how much you've been able to get into the key ASM centers. I'm wondering how much overlap do you think there is with the PIONEER and the HARBOR ISM population? And then, if you can maybe talk a little bit about the disease education efforts.

Have you been -- is there any inbounds on ISM? And if you can maybe discuss, if you've been seeing increases in D816V testing? Thank you..

Sure. So the -- as I said earlier, the 70 key centers are certainly where we see -- we think a lot of advance SM patients being treated about half in the United States. They also play a key role for non-advanced patients.

And I think that, again as I shared we're seeing that in real time as we're out engaging with sites where we're seeing advanced SM patients being identified, but then also non-advanced patients who are interested in treatment.

Certainly, our goal at this point is to facilitate enrollment in clinical studies for those patients, whether that be PIONEER or eventually HARBOR. So we're going to be following up on that interest. And then as we get into the ISM market more generally, allergy as I said becomes a broader -- a more important call point.

But I think these 70 centers still will help really -- they play a role in diagnose is certainly as many patients and I think will be a good sort of foothold for us as we ride on into the nonevent market..

Great.

And then is there a way for you guys to track the D816V testing as kind of -- you mentioned that that was a bottleneck or one of the main levers for patient identification?.

Yeah. So this is something we will be looking at over time. I mean, the difference -- I think a subtle difference here, if I even compare to say GAVRETO where we're the -- I think the goal there is to get patients who are being diagnosed with lung cancer appropriately tested for a mutation.

Here, our label is obviously not specific to a mutation, but we really see the testing as being kind of the key to facilitating increased diagnosis, particularly for non-advanced patients. So it's obviously early. We're just in the market commercially. So I think something we'll certainly have a sense of over time.

And the way I think we'll see that play out is growth in the number of non-advanced patients that we can really identify and see. And so that's a place that we will continue to focus in terms of disease education, market development et cetera between now and when we have a anticipated approval there..

Great. Thank you very much..

There are no further questions at this time. So I'll hand the call back to Mr. Albers..

Thanks, operator, and thank you all for taking the time to join us today and for your continued support of Blueprint Medicines. And we look forward to updating you again soon. Have a great day. Bye-bye. .

This concludes today's conference call. Thank you all for joining. You may now disconnect..