Q3 2022 Blueprint Medicines Corp Earnings Call & Investor Day

Yeah.

Okay.

Okay.

Yes.

Okay.

Okay.

Yeah.

Yes.

We can say H senior Vice President, Mr relationships, which Jim Baker.

Good morning, everyone.

Thank for joining us.

Oh boy.

His birthday.

I suppose that you are in your morning with us.

Our board and.

Employees, who contributed with Apple pay.

And a lift pump.

Yeah.

Good morning, without planning for thoughts for the third quarter.

Great presentation today.

Excited to share a number of projects and our vision.

Keeping precision at scale.

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Kathryn <unk>, our Chief Executive Officer.

Collectively our chief commercial officer.

Or he used our chief Medical officer.

Doctor food.

Hi, Bonnie.

R&D.

Firstly Parker, our Chief Scientific Officer, and Christy Rossi, our Chief operating officer.

Our Chief Financial Officer.

Zipcars available from Keybanc.

Once they come off.

<unk> at this point.

The swing procurements divided up to two seven.

First of all talk about sprint.

Frankly to get to patients the semi test and protection will conclude with a panel discussion and Q&A with breakthrough disease experts.

We'll then take short 10 minute break.

After the break or partnerships, which will include presentations by pre.

Grams per Egfr mutant lung cancer, and a portfolio of restriction for focused strategies.

As part of patients will have to spend with company leadership.

<unk> is on track from time perspective, we ask the people for your questions. So we got six minute period at the end of October .

For any of our subsidiary <unk>.

My questions are.

Directly during Q&A and we will.

Dennis.

No.

Who can make important papers effect.

And Mr Stroup skewed, our SEC filings, including our recent April .

Risk factors.

Our 10-Q filings for the third quarter, which will be fine.

S markets.

Now I'd like to introduce at Hopkins, our Chief Executive Officer.

Good morning, everybody.

The voluntary.

Okay perfect.

Most likely extend a warm up to offset the size.

And thank you for that.

It has been.

Okay.

With just over 10 years ago.

And hopefully that preceded it.

An improved and extended.

Right.

Sure.

Yes.

Thank you.

I guess my flippant.

Yes.

This is maggie fiction.

Too much space and beverage sector.

Holiday.

That target the.

And.

Okay.

Oh wait.

Falcons improve outcome for patients.

At the same time dramatically.

Good luck.

Bye.

Difficult.

Sometimes it's tolerable side effect.

<unk> occupancy.

Thanks.

Perfect.

Let me now.

We are very.

Todays commentary.

Please elaborate.

Great.

Okay.

Patients directly.

Yeah.

Could we go back and what would the cheeks.

I deliberately.

Right.

Kip.

At the right time.

That's understood.

Individual picture, we have been active.

Excluding the PCC pictured here.

David Skippy, Switzerland anyway.

At this time I'd like to.

Right.

Yes.

Stupid travel.

Yeah.

Max out to the east.

Yeah.

Jennifer Fritzsche burckhardt supported with us.

Okay.

It just started.

Talking about.

So stupid a context.

That was one technical backup to pack away from you.

Sure.

With til Tucker-bag.

Capital.

She felt metrics too.

Each of proportional debt.

That's opened up different protests.

Telling them.

Mitchell and their lives.

Jeremy.

And I'll turn.

Oh <unk>.

The first chip lockups attached to ever happen.

It came up so quickly.

She can do before she lost consciousness.

With texture.

Okay.

But I'd be happy to talk.

Mr.

Are you able to locate her quickly.

He fostered CPR, where she could sweep.

With this influx of tax.

Her diagnosis.

And systemic mastocytosis.

After her checkout that she.

As you'd expect.

Isolated.

Talk about excuse me license on.

Some spot definitely.

And as to repay processed work like it used to be before.

Thanks.

Joe talked about the impact of that.

Assembly.

Germany had a tougher if blackstone.

Very quickly.

Okay.

Mr. Avi Petrohawk.

Her technical nonwovens.

Superior activity despite the political.

Political cycle.

Scratch project.

So park.

Average commission defied the Doc.

Secondly, a relief.

As she desperately wanted to have a lot of it.

For the travel sector.

Two questions.

Quite a feat.

He told me that she could have.

W. R Berkley speaker accounts.

She felt strongly this.

Mr wanted to meet.

Hey, guys.

Yes.

Sheila Mcdonald's for the first time.

Sure.

Yes.

Peter Congratulations.

Pope.

If you look at it.

And.

Yeah.

Okay.

Once it get next year.

Right.

Events.

School event.

She could go grocery shopping.

She is going to impact we would have done it.

Importantly, she'd like to divest.

Anthony Perkins the child Tabak.

Or they are no longer committed here.

Sure.

And losing them.

We will get directly from 50 shortly.

Yes.

Lucky.

Mark It's Tony here.

Talk about cities clinical catch a few of the investigator.

I want to keep it.

And the partner clinical platform.

Two key storage historic let's start it.

What motivates us every day.

It keeps our tablet print.

The foundation of innovation.

Yeah.

Shifting to shake out.

Difficult at important medical problems.

Okay.

Sure.

Health care providers.

No.

If treatment options.

For Richardson Eplex disconnect mastocytosis.

Baxter.

One more.

Alright, guys.

All right.

That's a pretty important the first one on the pretreatment pursued big Temptation Fletcher.

In fact, it's sandeep.

Patients would not affect us.

A tremendous near term growth opportunity for Abbott.

But it's a really important topic at once it will skip some details at this point.

But another goal we have for today.

Understood.

The treatment.

One potent blueprint.

Prediction.

Yes.

Did it second.

Victor.

Perfect.

Understood perfect in early November 2019.

We have significantly paired subject.

And we can build on.

Enterprise capabilities and infrastructure.

We will check with you today.

I believe our blueprint.

Peanuts at the old company.

We believe differentiate us.

We reported leprosy pathogen to.

Due to its impact on patients globally.

And we will also kept with you today, our vision of what we are aiming to achieve.

Five years.

Okay.

And my first secure C O blueprint medicines.

With opportunities to Catherine.

And with Topeka capital.

I've never felt more of an effect.

But what we can achieve.

Okay.

Sprint form to outcomes.

Thousands of patients globally.

So let's start the conversation.

What would you have achieved in the last 10 years.

It's remarkable.

Sure.

When it's time to each one.

One of these.

We have been nominated.

Therapeutic development candidates.

She footnotes of bottom line.

Benefits.

Eight.

With development.

Our team.

Or.

<unk> collaboration.

It's for feedstock for Berry.

But shifting market opportunity.

We've kept a cottage.

Industry.

With 80% et cetera.

Clinical proof of concept.

We are particularly serious medical conditions.

And we have developed important data.

That is electric five mbps.

<unk> definition.

It can be.

Yes.

Unless it's for years.

Our first patient.

And yet.

Okay.

We know that the one thing patients with breast cancer and rare diseases.

Yes.

We have no history.

By bringing to introduce two approvals from our labs and spirit.

Since our company.

Excuse me Mr Richards.

Vince.

Five.

FDA approvals.

That's like ours.

In this industry.

You're very perceptive.

This accomplishment.

At the poorly.

The confidence that we can impact more lives.

This portfolio of indications.

It also superbly anymore transformational medicines in the future.

Above and beyond our research and development capabilities. We have now also established commercial infrastructure.

Commercial stage company has been an important evolution for us at Blueprint medicine.

These are well positioned for near term commercial growth.

Thank you Keith.

Yeah.

The first is the opportunity.

We are pursuing.

We are ready to scale.

Mkay exactly at the medical needs of a substantially larger proportionate and updates.

Potential label expansion into narcolepsy and in adult care.

The markdown opportunity for AMETEK.

Across the spectrum of <unk>.

But it would be.

The opportunity we're pursuing today.

This could have blockbuster opportunity.

Currently is also our specialty markets.

We can ask better much better opportunity to economies of scale.

Only a modest increase in our field.

Yeah.

The same time.

<unk> and.

<unk>.

Great.

Two reasons beyond the deficit.

Strip luxury directly owned if Europe .

With partners to bring innovative medicines to patients around the globe.

The second key distinguishing factor you see them at all.

That's right.

We have three commercial experience expertise.

We have established cadence.

Surgeons professionals.

With disease awareness.

Appropriate factor.

Treatment option.

Picture.

We have the right team of people and it was aimed at supporting that I spoke to Cowen.

<unk> impact.

Okay.

Okay.

And third we have deep expertise.

That will enable us to particularly.

Our leadership in this area.

We are definitely in the direction of innovation in this space.

Subsequent solid square Gilbert.

CB defense.

And we are not mixed Arizona.

Interaction of our field based teams.

Cannot underestimate how important.

It is painful.

<unk> group of the patients were treated with Vascepa.

She came to us that we play both understanding.

5% occupancy.

And typically and understand the digitally.

A precision for treatment of patients.

And we bring them back into work parity with development.

First to.

Developer.

Tom.

Okay.

It was published in <unk>.

And relevant data.

For all of our health care partners.

Okay.

These pages.

Yes.

We can go.

There is a commercial stage company.

We need to fix.

Every single day.

Okay.

We are pursuing.

Okay.

Reasonable and achievable near term.

<unk>.

And by consistently municipals.

What we will be focused on doing.

As we drive our store performance.

Steady for you today.

Offered.

It's incredibly compelling value proposition.

We will also provide details that support the value proposition.

And our strategy for driving growth and delivering value to all of our stakeholders.

Thank you.

<unk>.

With our existing commercial portfolio.

With each to drive the revenue acceleration with potential expansions.

Mcnabb the sector.

Do you have a certain type of Bellevue.

Tangible near term opportunity.

Okay.

Today, we announced our Q2 results.

Our overall polak opex.

Which is the high end of that range.

A revised upward our rep.

Our revenue guidance for the year.

<unk>.

Felipe will walk you through the reason for our data shortly.

Portland.

The second.

Value proposition is.

This portfolio.

Best in class.

He spoke therapies.

I think that's important.

Important medical problems.

Infrastructure groups of patients.

This portfolio will enable us to scale our impact on patients.

I think we're still clinical portfolio.

Drug discovery platform.

This of course generate new programs with higher than industry average probably success, we saw in the previous slide.

It will.

We continue to drive long term organic growth.

The diversity of our fundamental value drivers creates numerous opportunities for growth.

<unk> perpetual.

All aspects of our business.

As a fully integrated company with critical mass, we just amplify shortly.

Relative to that getting the treatments for patients.

At a larger scale is just the beginning.

Okay.

What do you think will talk about precision at scale.

This is gil.

We will double our impact and Pat.

I want to zero in on the global spot.

In the next five years.

Please open without being able to have four approved medicines.

There are very few companies, who have been able to achieve that.

And a quick why positions with precision.

To meet or exceed this goal.

And it's a product suite into established leadership position to have additional therapeutic area.

Okay.

We doubled the number of programs, we are pleased with clinical development.

Yes.

Im pleased with number of therapeutic development.

Daniel.

What can be achieved with both mean infill Brooks sharps.

If he thinks it will be surfaced, almost 20 times for patients with gene.

Since there are no.

I just wanted to pick up and still get to that.

With the confidence.

These goals because of the population.

Another way to think about our types of attack at the objective we have put together it's been the practice before all have been asking us over the past few months.

And a quick.

The key question.

Martin.

Perfect.

What is the opportunity.

Magnetek notebook and tablet current experience.

Mcnabb launch and formats.

The second.

Did you have a winning approach.

Sure Chad.

For patients with Egfr driven.

And the third.

How do we leverage our expertise and infrastructure to drive continue installations bankrupt over the long term.

We've answered all of your questions to share with you today.

The children.

Yes.

We are well underway.

Able to treat the majority of patients with FX.

Yeah, we are.

David will be.

Therapeutic category.

So Peter Becker.

For detail.

Our conference has ended.

From opportunities to expand it impacted indicated if nothing bad sector.

Because the deeper default market insights with mckechnie.

And importantly, based on our strong clinical profile.

From the pioneer study.

Federal protection.

FERC practice in April .

Patients with moderate to severe asthma.

Your next opportunity to hear from St.

And to treat patients with it.

Including Doctor practices.

The project photography, and particularly <unk>.

Second question.

Do we have a winning strategy.

Just a couple of patients with Egfr mutant lung cancer.

Yes, sure as best we can.

We have some egfr egfr opportunity if our sites it was our strategy our emerging data.

These capabilities.

We are progressing our comprehensive portfolio.

Digital has transformed the treatment.

Part of it the non small cell lung cancer.

Who will provide an updated overview of the portfolio.

If you're a big girl, who can get bid opportunities.

Importantly, our strategy is comprehensive.

But it's also modular.

He can achieve significant commercial success with each quarter.

It took them off the books.

Welcome.

W.

<unk> treatment.

Through a combination of both compounds at the first line standard of care.

As for a third question.

We will turn to recharge and how we're building on the track record of success.

Firstly would describe help yourself.

Separate efforts.

Given the range of significant pursuit.

It took our offer is very impressive research purposes.

Critical also described how we are integrating in a robust scientific discovery.

With our clinical expertise and our commercial.

Commercial capabilities and infrastructure to build a portfolio with synergies.

A great example.

It's a new program.

Pardon me.

I want to thank you all for joining us today.

Excited to share with people our perspective.

Dry blueprint success over the next five years.

Before I hand, it off to him with his background luxury directly from patients.

Two P M.

Thank you Mike.

Okay.

Yes.

Uh huh.

Uh huh.

Please go ahead Sir.

Jesus.

And we have people working.

Thank you.

I started the FCC, Mr. Traynham editorials Mr Pittman.

So they are now concluded.

Next please.

A bunch of work.

H E B.

Understood.

Yeah.

Revenue for the company.

Super.

Sure.

Mark to market.

Okay.

Thank you.

I was told.

Scott or Jim.

Yeah.

Okay.

Albert.

Probably just won't rehash.

Okay.

Okay.

T V.

But his hospital.

Okay.

And.

In critical care and <unk>.

Yes.

Because every street corner.

The doctors who today.

I will comment on that.

Bruce.

Good luck.

Newspapers.

Olivia.

Suddenly snowball at least.

Hum.

Yeah.

To put as much as you said.

Okay.

That's helpful.

Great.

Farquhar.

Our renewed.

The next piece of it.

Right.

It took interstate of fear, Arizona Irina histamine.

I was on heavy doses of steroids.

No.

We had to keep <unk> at all times, because you never knew what was coming next.

Your new.

What new thing I would be reacting to that cause anaphylaxis.

The youngest daughter was eight <unk>.

It's not our responsibility for an eight year old.

Pretty much all the doctors and nurses are on Google.

Looking things up I also carry some literature with me in my purse that I give them and Theres some materials for MA Mr. Sentosa Society.

I give them so they can look over.

So challenging is a lot of time getting proper care. The biggest challenge that I have faced with us them is being.

Being forced to retire before I officially wanted to retire.

I know a lot of people who work in the hate their jobs.

I'm going to love my job when I had the sub worthiness before my long term visibility and social security disability kicked in I have to go to Nok Spanish.

So why was no pay for three months, so I have to rely on the help of moms My Grandma to a little bit degree and my fiance emotionally at fuse.

It's like a grieving process.

You've lived this normalize for 35 years and then suddenly.

Just a few times.

You can't know enjoying things used to your Missingham things with your kids.

They agree he agree for.

The normalcy the east.

We are terrified that you're never going to happen again.

Your old life did.

You Miss it.

There are so many mills.

Uh huh.

You can't get back.

But.

I'm trying to make up for them.

I decided to participate in the trial because my disease had progressed, which we found on the bone marrow biopsy, Berkeley symptoms have gotten.

Much more unmanageable.

To speak because.

Didn't have any hope any other medications.

Treatments to many times.

There was nothing.

I was just.

Waiting like I said waiting for that last time initially.

Initially when you start the trial drugs, a little bit of an adjustment period. So I did have like some nausea.

So we had to easily zofran Dreamer, but then once my body got used to it. It was it was great my triggers.

Certain ones are better certain ones are about the same I can eat tomatoes, again, which is miraculous because they lows battalion booth so there's that.

But I still have the same issues, so I still have problems with the perfumes.

Cleaner.

Since I've been on the trail drug I have not had any influences. So we're going three years now knock on wood with no influences. So I. It took me several months.

But.

I'm feeling so much better my bone pain.

Is almost nonexistent.

Phil.

I'm not 100% back to my old now, but I'm.

I'm not having anaphylaxis.

Uh huh.

Hi.

Pad.

The spot all of them my body.

And now probably have eight or 10.

It's a pretty big win.

Pretty good outward expression of what I know is happening inside my money.

I'm proud of the fact that I'm able to attend live music events.

And I have my mom is actually my best friends. So we hang out all the time and do a lot of Huntsville, I only get three or six months out a year because she leaves me for the winter photo Marsh's here, we do a lot of Huntsville is like rock concert.

I'm not speaking of mobile.

I want to move down.

Yes.

It comes in a lot of people take for granted.

And I don't know how long ever Jacobson Brandon again.

Okay.

<unk>.

More than I have words to express.

[music].

Good morning, everyone.

My name is Selena Lee and I'm, the Chief commercial officer.

That patient video we just saw today is an incredibly important anchoring moment of our day.

This is the type of patient impact, we aspire to achieve for patients living with systemic mastocytosis.

Susan Melanie story provides a great example of the debilitating impact S. M can have on patients and families.

We first shared Melanie story three years ago at our Investor Day.

And since then advocate has truly impacted her life.

We aim to make this type of impact on many more patients living with systemic mastocytosis.

And today, we're going to share how we're going to do that.

I've been involved in Ava kits development and commercialization since the beginning.

And from the start we've partnered closely with the S M community.

Resulting in a winning product profile that addresses the needs of patients providers and payers.

By targeting Chip V 816 V F.

<unk> has achieved profound disease modifying activity.

Enabling deep durable responses in advanced disease.

Clear symptom improvement in non advanced disease.

And a favorable safety profile that opens up the potential for chronic lifelong treatment.

With the strong product profile now in hand, we feel a tremendous sense of responsibility to deliver on this promise for patients.

So here are the most important take home points I'll speak to today.

Eva kit has the potential to benefit patients across the spectrum of systemic mastocytosis.

This represents a compelling commercial opportunity with blockbuster potential.

We are early in this journey.

Beginning with the advanced SM ongoing launch.

With a strong higher readout, we're now well positioned to move into non advanced F M with the anticipated approval and launch.

We are very well positioned to launch Ava kit for non advanced SM.

And then my 15 years of commercial experience I can't imagine a more exhilarating moment, then where we stand today.

The culmination of many years of development effort with that early optimism to seeks to address patients across the spectrum of S. M.

And yet we're still only getting started and what truly inspires me is the opportunity to work with our commercial and medical teams, who are out there living their patient focus and persevering everyday as they engage with providers to change this treatment paradigm.

And so we are early in this journey, starting with advanced SM.

And we are moving in parallel to prepare to capture the much larger non advanced SM patient opportunity and there are several levers for continued growth over time.

Before going into this in more detail, let's just step back and take a moment to examine some important differences between advanced SM and non advanced SM.

Advanced of them is managed primarily by oncologists.

An ideal treatment goal is to improve the overall survival of these patients.

The disease is highly heterogeneous with three distinct subtypes and most of these patients have S. M along with an associated heme neoplasm or a H N.

We're a proliferation of additional self creates complexity in the management of these patients today, it's a highly medically complex disease.

Non announced S. M is much more prevalent it's manage primarily by hematology oncologists as well as allergist immunologist, who are highly attuned to patients' symptom burden with a treatment goal of improving their quality of life.

Non advanced SM has a much more homogeneous disease biology, one disease, one cause chip D 860.

There is heterogeneity that results in terms of the severity of symptoms and the types of symptoms that present from patient to patient.

And so let's dive in first by talking about our efforts in advanced SM.

In the context of our performance.

And so taking a look at our first year of launch of Eva kit in advanced SM.

We have established <unk> as the standard of care in patients and patients who are treated for their advanced SM and our first four quarters of growth illustrates this.

We've reached a point in our launch cadence where continued growth requires on the requires the ability to grow the number of treated patients most of whom have S. M as well as that concomitant H N and will speak to these challenges in a bit more detail.

In Q3.

We generated net product revenues of $28 6 million.

This represents 65% growth over Q3 of last year.

But not the same degree of growth we had seen in the first four quarters of our launch.

If we laser into the key drivers and challenges behind our Q3 performance in more detail.

On the driver side.

We have in fact further strengthened <unk> position as the standard of care in treated advanced SM patients.

We have grown the market share of patients who are treated from slightly over 50% to approximately 60% within Q3. This type of market share growth is impressive within one quarter.

Our team has accomplished this by growing the share of treated patients starts and switches to 75%.

And importantly, the number of advanced SM patients on therapy continues to grow.

Finally, we continue to broaden and provider experience with Eva Kid growing the number of total accounts treating to 350 since launch.

Adding more than 50 new accounts.

During Q3.

The key market challenge, we are focused on is that the initial penetration and patients with S. N. H N has been lower than other subtypes.

And this goes back to the complexity of SMH Ed.

We're today providers must decide between treating the S M.

We're prioritizing the HN.

Which there historically used to doing due to the lack of effective treatment options.

We are up got where with these market insights in hand, we are updating our full year revenue guidance to $108 million to $111 million.

This represents two fold year over year growth.

And we expect this growth to be able to continue.

Albeit at a more measured pace within advanced SM.

There are three important reasons to believe in this continued growth within advanced SM. The first being as I mentioned, the total number of treated patients continues to grow.

Secondly.

The majority of S. M. H N patients are anticipated to be addressable with <unk> overtime.

And finally, the real World experience has been very positive with duration of therapy trending still towards 18 months and.

And importantly in the patients who have recently started Ava kit treatment. These.

These patients are trending towards an even longer duration of therapy.

These patients are also primarily PKI knife.

We have taken time to assess the market dynamics at play in this S. M. H N highly complex patient subset and we are applying these insights to an action plan.

Our team is redoubling our efforts focusing on this enhanced action plan and the plan has three important components.

The first is provider education, using both the efforts of our field team and peer to peer education.

To inform on the rationale to treat b.

BSM the urgency to treat the S M component, especially in these SMH on patients.

Secondly.

We have rolled out enhanced real time patient level data alerts to enable our field teams to understand exactly where there are advanced SM patients in need of a new therapy, who are much more likely to start an Eva kit therapy.

And finally, we continue to drive forward our data generation efforts to follow long term follow up on advocate.

As well as to embark on combination studies that will be important to treat the S. N H N components.

In addition, we are incrementally expanding our field teams in preparation for the non advanced SM launch.

And this will broaden our reach to address an additional number of providers, who are treating advanced SM patients today.

Let's dive into two of these key initiatives and a little bit more detail.

On the left hand side of the slide you can see the significant overall survival benefit Ava kit has shown compared to best available therapy in a retrospective study.

This data was recently published and just this month actually I should say just in October .

With added to the NCC guidelines, which will further increase the awareness of these important data.

Over on the right hand side.

We have leveraged machine learning to increase the predictive power of our patient level data alerts.

That we equip our field teams with.

And using these tools now we are able to identify patients who are now more than tenfold likely to start on Ava kits.

Importantly.

This enables us to continue to move forward. These types of tools enable us to continue to move forward with and highly efficient and effective commercial model because our teams know where to go to engage with providers, who are engaging who are managing these patients in need.

So looking forward.

We expect to continue to grow it.

If we applied pattern recognition from other rare disease launches, we wouldn't be surprised to see some variability from quarter to quarter.

But the year over year will be strong.

And most importantly, our key inflection point that we anticipate next year.

The anticipated approval and launch into non advanced SM select now dive into that in more detail.

The pioneer readout in August has been one of the truly most rewarding moments in my career.

We are now shifting our strategy to prepare for non advanced SM.

And let's remember those key differences between non advanced SM and advanced SM. The first is size non advert nonevent. This M is far more prevalent.

The second is there's little to no disease heterogeneity in terms of the underlying cause of the disease.

And the third is that goal of treatment is to improve symptoms and quality of life and we have not only hematologists oncologists, but also allergist immunologist, who are heavily involved in managing towards that.

Okay.

In my years at Blueprint. This opportunity has never felt is tangible as it does now.

And let me tell you why.

So one of the questions that we commonly get from investors is how many patients with non advanced at them could be amenable to treatment by Eva kit.

So we've looked at this question closely using the most comprehensive claims data set in the industry.

And what we have found is that we can see within the U S 7500 patients diagnosed with moderate to severe non advanced SM.

Who are diagnosed actively seeking treatment and receiving therapy with symptom directed polypharmacy today.

We can look further using the resolution and the power of our claims data to further stratify. These patients into two disease segments more severe as well as more moderate disease presentation and we've done. This looking at factors that include the degree of burden of disease. So the frequency of anaphylaxis organ involvement.

As well as the degree of polypharmacy burden, so whether the patients are using more teekay is side of reductive therapies or long term use of steroids crumlin or antihistamine.

We anticipate the earliest adoption in our launch will come from the more severe.

Severe segment of these patients.

Followed by adoption into the more moderate patients overtime.

This level of resolution into.

Ah patient population, who are in need and seeking new treatment options.

This puts us on a clear path to achieve the potential for Ava kit.

So let's dive into these data in yet more detail and so what you're looking at here.

Is individual patient level journeys with systemic mastocytosis.

And so we've shown the journey for four representative patients with advanced SM on the top followed by a severe non advanced SM patient journey, a moderate non advanced patient and another non advanced SM patient.

And so every single Dot youre looking at represents an interaction with the healthcare provider.

Or a change in therapy, a tuning of that symptom directed polypharmacy to try to improve symptom control.

There are also dots that indicate acute events such as ER visits.

Or multiple additional prescriptions of Epipen I'll direct you to the second row, where the severe non advanced SM patients has had multiple episodes, where these patients had to be prescribed additional epipen.

And in the third row of moderate non advanced SM patients, who had multiple interactions to adjust their symptom directed park polypharmacy, including Epipen prescription.

The first important take home message from all of this is how it illustrates.

Credible high burden of disease within these patients.

And the second important take home message is how actionable. These types of insights are.

Again by having this individual patient level resolution, we are able to provide actionable alerts to our field teams.

So that they know when and where to engage with providers who are treating these patients in need.

Again, maximizing the efficiency of our commercial build.

This is part of our blueprint edge.

Let's move next to talk a bit more about that launch strategy.

Our launch strategy is focused on the ability to drive growth across every single phase of the launch.

We're actively engaged in prelaunch preparations and we're getting ready for launch anticipating mid 2023.

Beyond this there are several levers to continue to accelerate growth deepen provider experience and broaden adoption is a broader patient segment overtime.

The three core tenants of our launch.

Our highly targeted provider engagement in order to build the disease awareness the.

Agency to treat and the rationale for Ava kit.

And secondly to leverage our strong access foundation to ensure unencumbered patient access to therapy.

And the third quarter Tennant is patient engagement, we know that patients are at the center of their care and so educating and empowering these patients to seek more information about their disease and about treatment options will be critical.

So let's dive into each of these in a bit more detail.

On the provider side, our strong analytics once again enabled us to segment the providers, who are treating the 7500 patients visible and claims data today into three distinct segments.

And there are three ways that our go to market model is going to enable us to interact and engage these providers in a highly targeted and efficient manner.

The first is in the prelaunch phase, where we're focused on engaging these top 350 providers, who are sort of on the top of the peak. These providers are managing 1500 patients who are actively seeking care today.

Upon approval will equip our field teams with patient level data alerts that enable them to engage with providers across all of these segments, but at the right moment in time when they are treating these patients in need.

And finally to address the tail of the providers who include additional referring specialties like Gi and derm.

We'll apply methods such as non personal promotion and other cost effective approaches to educate interact and.

And engaged with the scale.

So turning to patient access.

So two questions, we get frequently from investors or how are you going to price advocate and how are you going to ensure good patient access to therapy.

What patients and providers truly care about is access and affordability what will be the cost of this medicine to my patient how easy will it be for me to get this medicine and how quickly.

Importantly, our model is set up to address both of these important drivers.

When we look at the advanced S. M. S N market today and engage with payers, we see that payers don't currently distinguish between advanced F M and non advanced of them.

That's an important point as the access to <unk> today.

For advanced SM is extremely favorable and provides a strong foundation.

And so let me walk through four important points when it comes from an access perspective.

The first is all five doses of Eva kit are available on the market today.

And they are being reimbursed.

They are being reimbursed with virtually unencumbered payer coverage.

The third point is that we see an exceptionally rapid time to fill Ava kit in less than five days.

These types of metrics are among the best in the industry.

And the fourth important point comes from our early research and engagement with payers.

That show us that payers understand <unk> is a rare disease.

They understand that Eva kit will be the first and only approved therapy for non advanced SM at launch.

And they don't anticipate managing this category in a way that restrict access to appropriate patients.

The bottom line is.

We expect strong coverage.

And building on this are your blueprint patient support program.

Dreamliner the access process for patients.

When we look at the number of patients who are receiving <unk> approximately half are enrolled in your blueprint the succeeds standards for oral oncology.

We also see that the majority of patients receiving Ava kit receive co pay assistance when they qualify whether or not theyre engaged in your blueprint.

And so the bottom line of patient access is a critical priority for us at blueprint.

And the access capabilities, we already have in place provide a strong foundation for non advanced SM.

Moving towards patients and caregivers.

And educated patient can be a catalyst for treatment. We saw in the patient video how Melanie was carrying literature in her purse. So that she could educate the providers who are caring for her and so it's incredibly important to engaged with this patient and caregiver community.

One example of how we've done this is our it's something patient and caregiver education campaign, which launched earlier this year in March and has secured industry leading metrics in terms of the outreach and just this is truly an illustrates how highly engaged this community is and how hungry they are to seek more information.

Beyond this we are also engaged in long standing partnerships with patient.

With patient advocacy groups, such as the mast cell disease Society for many many years.

And so stepping back.

There was a highly tractable path to address the needs of these patients who are diagnosed that we can see today.

And beyond this.

There are multiple opportunities to drive further growth and patient impact with Eva kit.

I'm proud to share some of the metrics that we've seen as blueprint has partnered with the S. M community over many years, resulting in a steady growth in the number of SM patients who have been diagnosed and who are visible to us in U S claims data.

One of the things I'm. Most excited about is the ability to help these patients who today are wandering through the healthcare system looking for a diagnosis, helping them get to that diagnosis faster and helping them find better treatment options.

And so in close.

We see a clear path to a highly compelling opportunity.

While in the near term we're focused on the advanced SM ongoing launch and growing that treated patient population. We're also focused on the far greater non advanced SM opportunity.

We are exceptionally well positioned for this launch.

With a winning product profile.

Leadership experience from nearly a decade of involvement in the SM disease area.

And finally, a highly experienced team who are in the market today already for advanced SM and engaging with providers.

So thank you for your attention and with that I'll transition to Becker and our key opinion leader panel, we're going to share more about why we're so confident in <unk> profile and non advanced SM.

Thanks Serena.

Yes.

Good morning, everyone and Becker Hughes Chief Medical Officer.

It's good to be back in New York I did my training here, how is that New York Hospital for residency and I saw my first cancer patients at Sloan Kettering, What I appreciate about New York is give me the facts and I know Thats Whats you are here for so today, we're going to take a deeper dive into non advanced systemic mastocytosis, we're going to look at some pioneer data.

Putting a bit of new data and this is to help you put into context.

Did you hear about from our.

Physicians that have treated systemic mastocytosis mitosis for many years.

But before we do that I wanted to provide my perspective on this program.

So I've been developing drugs for 17 years, and I've had the privilege of bringing two patients three drugs that have been transformative for breast cancer leukemia and lymphoma.

I'll tell you this is different and the reason it's different is because for the first time patients in an underserved population has an option or will have an option that modifies the disease and improve their lives and what Youll see is this is a serious debilitating disease.

So.

In that process, we are defining how to treat the disease. We're learning a lot more about the biology and this includes the complex biology of the.

Advanced Assam, where patients would like to have two malignancies at the same time, and then a different kind of complexity in the non advanced SM, where a single driver drives a number of different types of symptoms and we'll get into why that is in a moment.

And so we're learning more about the disease and what we're really starting to learn more about the impact on the patient and you saw a couple of patients talking about this today, but what youre going to also learned today. This is not these are not outlier patients. These are typical non advanced patients and so we will hear from Eric our treating physicians to provide more evidence about that.

So.

In order to.

<unk>.

That's the understanding and make sure they're all on the same page, we're going to take a look at systemic mastocytosis. So we understand why such a devastating disease and how these mast cells are causing such difficult lives for these patients.

So first we got to think about what our masco is and why it's here Marcellus through the first line of defense for.

For all of us against really foreign invaders, and so there aren't many of them in the body, but they exist where you interact with the outside world. So theyre in the lungs in the Gi tract in skin and in the blood to a certain extent and they grow or they come from the bone marrow and so I think of these as <unk>.

The Navy seals of immune system, because they have to be ready for any attack and they have to be able to react very quickly and they don't have time to divide and migrate and so they have the most powerful armamentarium in the immune system in their granules and what they do is when you get an <unk> thing or you eat something.

Can you just should meet their only goal is to make sure that that substance is diluted and out of your system as quickly as possible and so youll get itchiness to get that figure out of the skin, you'll get data dilatation, and you get wheel and flare in your skin and highs and this is all to redirect this has been an outside away.

From where it's sitting in your skin and the GI tract you see peristalsis you see you see get pain from the inflammation from the release of the system means and leukotriene. These are the most powerful chemicals their immune system has.

And so that's the normal function, but then when <unk> kit mutation occurs in these myself the kit molecule. The <unk> protein is the control center for these Marcellus and so these with the mutation our always on they are releasing granules with the little of stimulation or sometimes no.

Stimulation and this becomes a chronic inflammatory condition because these cells not only caused visa dilatation, but they also recruit other immune cells to the area. So I'll show you in a moment how this shows up in patients that have had systemic mastocytosis and the non advanced form, particularly those who have had it for a long time.

So the first place that often shows up is in the skin as we've heard there'll be a little brown spots, but these arent just hyper pigmented lesions. These spots have a lot of mast cells in them and that's why you see dairy ursine barrier side is when you just caused physical stimulation of you Rob the scan you get a release of Histamines in it.

Yeah, Hi.

So these are massive in Marcellus and are poised to release their mediators in on the top right of the screen you can see the subcutaneous tissue and the chronic inflammation that you see in these patients.

And I'll talk about anaphylaxis Sue can you talked about having anaphylaxis that was the worst that any of the VR had seen and the reason that is so bad we all are familiar with people with peanut allergies or they get a lasting and they get the swelling in any difficulty breathing, but there is a particular kind of anaphylaxis for these.

Patient tab, which includes hypertension, so not only can you not read but you don't have any blood pressure.

And so it can be particularly scary, particularly life threatening and this can happen over and over again for patients. So they use multiple ipads in many cases and they have being variety of worrying about walking through department stores smelling, some perfume and having this kind of a reaction in the up either in just in the ER and Thats, a good day or in the ICU.

On a bad day.

So let's talk about the matter I said that these cells are prevalent in the Gi tract. So what that looks like if you see the bottom left of the screen you will see the coming of the GI tract and this is the chronic inflammation.

Turkey described when she would eat she would get belly pain, and then the diarrhea would come afterwards imagine trying to lead a normal life and go to work and you knew that when you went to launch youre going to spend the rest of the afternoon with diarrhea. Despite all of the medications that you might be taking so chronic inflammation in the Gi tract and really debilitating diarrhea nausea.

Pain in many patients.

So I said b cells are produced from the bone marrow. So as they continue to divide and if you don't stop the actual kit mutation from causing the cells to divide they will continue to divide in and go into other tissues and that's why this disease often gets worse every time, so what youll notice.

X Ray to the bonds is theres not a lot of calcium there's not a lot of white and thats because the Marcellus had started to eat their way through the bones in this patient with non advanced systemic mastocytosis and it causes bone pain than young people will have fractures as if they had osteoporosis as late in their life.

This is.

This debilitating and they can't do their normal activities of daily living they can't play sports and they experienced a lot of pain and it takes strong pain medications for it.

And then one of the most puzzling manifestations of the disease is the brain fog.

So.

Patients will describe and an ability to remember people's names to remember how to do activities that they do at work normally and so they can't function normally some of them are able to get by but they're nowhere near as sharp as they were before and for some of these patients. This has happened over the years before they are diagnosed.

And so they don't even realize that it's not just that they are getting a little older and a little slower.

Having rainfall from the disease and it's important to know so in this in this city scale Youll see some white marks these are white matter changes in the brain, we don't know whether it does or mast cells in the brain mass cells into <unk>.

Or it's just the mediators or some combination and blueprint we are going to figure out whether you need a compound that crosses the blood brain barrier to deal with these brain fog symptoms.

And then patients lose weight, they're tired all the time and as <unk> said some of them quote unquote living in a bubble. So they don't not only do they not have a normal life. They don't engage with our family with their friends with their colleagues. So it's a really devastating disease.

So with blueprint done about this.

The pioneer study was an ambitious attempt to do a few things one is to show that a targeted kit inhibitor that targets <unk> can reduce the disease burden can reduce the activity of these mast cells can therefore reduce the symptoms and therefore, it will change the quality of life for these patients and to begin.

To establish <unk> as a standard of care. These standard of care in non advanced systemic mastocytosis.

And we've done all these things so let me show you how we did it.

So on this slide you see the pioneer study pioneer.

Pioneer study was two parts. So on the top left what you see is part one part one was it was testing three doses 100 milligrams 50 milligrams and 25 milligrams of <unk> and non advanced systemic mastocytosis patients.

And the point here was to determine whether there was a dose response and what the safety of each dose was so that we can pick the best dose for Optum optimum efficacy and long term use.

You can see in part two in the middle of the Slide we took 25 milligrams randomized patients two to one to either <unk>.

Eva kit plus all of the medications that they were on already so best supportive care or placebo plus that's the fourth point of care. So it's not an inactive arm.

And we randomized patients two to one and then we looked at six months and we compared the mean reduction in symptoms between those two arms as our primary endpoint and.

And importantly, after that six month period patients who were receiving.

Receiving placebo plus best supportive care, we're able to rollover and received <unk> at 25 milligrams in and continue on that as long as they need it.

So today, we'll look further into the data and we will answer questions about dose selection.

And whether we left efficacy on the table and I can tell you now we didnt and I'll show you why and why the placebo arm did better than in part to then in part one and whether this was a typical SM patient or not and our clinicians will help us understand that and also whats clinically meaningful what's meaningful to prescribers and what's meaningful.

The patient.

And as Keith said I will show you a bit more data from the pioneer study and it's to bring into context, what you hear when you hear about the cases that are clinicians will present and also to help answer some of these questions.

So let's talk about the top line efficacy. So what you see here is the primary endpoint and multiple secondary endpoints all of which were statistically significantly positive in the pioneer study. This is not very common and it's particularly not very common in patient reported outcome study.

So these measure not only that mean change comparison, but the depth of response in patients and multiple ways of looking at objective measures of disease reduction remember first time, we're actually reducing the disease in these non advanced patients.

And so let's dive a little bit more deeply into the efficacy.

Primary endpoint mean change in symptom score you can see on the <unk> arm is a $15 six reduction in symptoms and this is only within the first six months of treatment.

And these patients have often had this disease for many years.

In the placebo arm, we saw a 9.2 point reduction and I can tell you that that was primarily in the first month or two of treatment and then it always a plateau in that score.

So, let's talk a little bit about placebo effect and why this might happen. So first of all it's common knowledge that when you go from a small to a large study you often will have a larger placebo effect in our clinicians who've done. Many of these trials have have told us about that and can continue to can talk to you all about it as well.

The other thing and I think this is probably the most important part if you think about the world. When we did pioneer 0.1 of the time when people didn't know that advocate can modify the disease. They didn't know that there is symptom improvement when you did modify the disease and so patients came in kind of not knowing what to expect.

And then when we did part two we had already seen the data from the advanced program showing profound reduction of disease in the advanced patients we'd seen the part one data where we saw all dose is showing a reduction in the symptoms that we really market and dramatic in some in many patients and the patients pay close attention to what's developing.

Some of our clinic clinicians have said they come in every time, I'd say whats new docs, what's coming down the pike that might modify the disease and so they knew that there was a chance that they could have benefit here and then they were randomized two to one so the fact that there was a more pronounced placebo effect in part two is not a surprise when you consider the environment.

Then patients that went on in the <unk> arm to treatment beyond that six months period onto a year you can see a further reduction in their symptoms and so this is chronic inflammation. Some of the symptoms takes some time, we chose six months to look at that primary endpoint, but there has been improvement beyond that and that's really important because we will see these data emerge every.

<unk>.

So let's talk about the disease itself and objective measures of disease Tryptase is what we've talked about so far.

So in.

In part two so let me talk a little bit about Tryptase Tryptase is a good marker of kind of how many mass cells. There are not a perfect marker, but it's a decent market and so you need to see reduction in Tryptase to know that you are modifying the disease, but what I can tell you and I'll show you. Some data on this in a minute is it doesn't track with either severity at baseline.

And so it's really common knowledge among patients and providers that youre tryptase level doesn't mean, if it's high but youre going to be really symptomatic and flow that youre not theres not theres a disconnect one of the reasons that might be the case is that you can imagine a patient.

Small number of very mature myself that are hyper excitable that can help high symptoms and then as those mast cells divide more rapidly they don't stay as mature and advanced patients, they're not actually very mature at all so the number of or the amount of histamine than we could try and per Marcel can go down so the symptoms and the tryptase can be quite disconnected.

But what we've shown here is that over half the patients have at least a 50% reduction in their tryptase level and this shows that <unk> at 25 milligrams is profoundly.

Impacting the disease burden by six months.

So let's talk about safety.

So.

In part two of pioneer we saw a pristine safety profile really consistent with long term dosing and this is important because patients are going to be on this drug we expect for a very long time. So a few things I want you to notice about this first of all the adverse event rate on both arms was about the same.

This tells you the disease itself and the drugs that are used at best supportive care will give I will cause a lot of side effects or a lot of adverse events. So.

The thought of giving patients high dose anti Histamines you can imagine I'm sure most of US taken anti Histamines and tried to have a normal day at work after that and it's really difficult because it makes you Sleepy makes you groggy and these patients are not only taking these things routinely but theyre, taking higher doses than normal.

So the sorry, the adverse event profile in both arms was about the same there was a bit more low level mild grade one edema on the Ava kit on but this edema was not something that caused people to move to dose suggests so it really was consistent with long term dosing.

No.

This safety profile is one that we were very pleased with and we now will be consistent with long term dosing in these patients, but we see safety profile like this the first question that some people some of you have asked.

Did you do did you use the right dose did you give them enough did you leave efficacy on the table. Let me show you why we did not.

So I haven't shown these data before this is new and this is from part one to.

A deeper dive into part one so on the left side of the slide you'll see the symptom reduction score for each of the doses tested in part one. So we've got 25, 50, and 100 milligrams and at six months Scott symptom reduction was pretty much the same in all three arms. So there is no dose response curve here.

Now when you look on the right side, we're looking to trip days and you can see there are a few patients with a bit more tryptase reduction by six months at 100 milligrams, then at 25 milligrams or even 50.

But this does not correlate with symptom improvement and that's giving you some reasons why that might be the case. So there is no correlation here between Tryptase reduction and symptom improvement we picked 25 milligrams, which was at least as efficacious as 50 or 100 milligrams and took it into part two.

Now in part two I didn't think that the question was finally answered in part one so we looked again and I can tell you I've asked for a number of exploratory analyses to look at correlations between trip days and symptom reduction and this is new data.

But what we saw in.

In this case, despite the large reduction in symptoms, we took patients with very high trip day. So in this case about 50 and asked whether there was a correlation between their tryptase reduction and there is simply a reduction and this correlation coefficient of 138 is pretty weak.

A correlation coefficient of one would be perfectly correlated zero means there is no correlation between three eight is quite a weak correlation coefficient. So again showing the tryptase does not reflect the symptomatology in this disease.

So how can we measure patient benefit beyond just system.

Well quality of life is something that we incorporated has been trialing a number of different ways and here I'm showing you. Some data from I will show you some data from the <unk>.

And the reason I chose the <unk> was because this is a tool used across a number of different disease types and so it measures a number of different ways of looking at your daily living your health stay how you're feeling are you anxious.

Anxious can you move around so it's a series of multiple questions that come up with a score between zero and one.

And what I'm showing you in the middle is that the average American has the score of about eight and then theres the disease intermittent porphyria that doesn't include a great deal of symptomatology and those patients are not that far below the normal American score of just over $8.

Now you look at lung cancer, and that's in the southern Middle Southern range in.

This also shows you that it's a very sensitive measure of quality of life and so a reduction in that 0.1 points is very significant.

And then you look at the patients on the pioneer part two and you can see that they have a lower score in the mid 0.6 or low six range.

Lower than even the lung cancer patients so what happened on treatment.

So the placebo arm reported about a 3% increase in their quality of life.

While the patient is treated with Eva kit at six months, we reported an 11% increase in the quality of life and this isn't just symptoms, it's like how they're living their quality of daily life and I can tell you based on other studies at other diseases. This.

Increase of 11% here is quite clinically significant it will show you more information or more detail on that at a future Medical conference.

We've got quality life, we've got symptom reduction another way to think about benefiting these patients is reducing the number of medications that they are taken.

So here, we look at the typical medications that are used in these non advanced patients and these are high dose high dose is good or given multiple times a day.

I've talked already about the sleepiness that you can get from anti Histamines and we've got steroids involved and then the Gi drugs are particularly worth talking about because.

Oral Cromolyn for example is one of the most load drugs that these patients are on it so let's take a bigger deeper dive into that.

So cromolyn is a mass cell stabilizer it doesn't do anything to decrease of mast cell burden, but it keeps the granules from a leasing as rapidly and it was initially developed for asthma and it's been re formulated into high concentration vials and patients have to take those vial and they have to delete them in a large volume of water.

Take them four times, a day, hey, guys taken before every meal and at that time.

Can't remember to take things once a day, sometimes much less four times a day and the reason I'm showing you. The stacker boxes is because a lot of these patients will labor medications out and put them on the blogs and this is just to show how much they have to do just to get by.

And so in pioneer part two we had 58 patients who were taking oral cromolyn at baseline for their Gi symptoms and.

And this is also new data.

So what we saw is just within that first six months there were about a quarter of the patients reduce their or cromolyn dosing.

It is important that it was in the first six months because these are patients who were trying not to change much because they didn't want to impact the primary endpoint, but nonetheless. This is such an onerous job. Okay decrease their intake of Qualcomm and no patients on the placebo arm did that.

So quite a distinction.

So.

That those are the new data I'm going to introduce today and now I'm going to bring up our experts in treating systemic mastocytosis non advanced systemic mastocytosis.

A couple of cases, and then after that we'll have an opportunity to ask them questions.

About the cases they presented.

Okay.

Therefore these chairs.

Yes.

Alright. Thank.

Thank you guys for making the trip.

Why don't we first start with a brief introduction and maybe you can talk a little bit about your practice, how many non advanced SM patients you see and whether you've had experience with Teva kit or not so let's start here with Dr. William So my name is Jim Widner I'm, a professor of Medicine at Washington University School of Medicine in St. Louis.

Yes.

I just started my 51st year on faculty at Wash U.

We have about 100 patients overall with mastocytosis.

And have you used David catches were not yet.

Yeah.

Professor Stephen that Yeah, Hi, everyone. My name is Steven and the dermatologists and allergists by training.

I wouldn't necessarily Chi hospital in Berlin, we have found.

Found an interdisciplinary mastocytosis center, a little bit more than a decade.

Joe.

Belinda and since then we have seen a couple of hundred patients with systemic and cutaneous mastocytosis.

Knowing about 850 patients in Berlin, and we see them on a regular basis every year and we do have some experience with IV because our center took part in the pioneer trial.

Great and thank you very much Ronnie.

I mean assistant Professor of Medicine at University of Alabama, Birmingham, Alabama.

Im a hematologist oncologist by training.

And <unk>, if the UAB MTN in Mastocytosis clinic.

I have experience with evaporated for both non advanced assay as well as advanced SM.

In addition on this slide.

The gateway on the pioneer study.

Thank you.

Before we dive into the cases, maybe I can ask each of you what stands out to you in this data and what you think is most important so maybe Dr. With Johnny if you start with yes, absolutely I think the the first and most important pieces of course, the symptom reduction.

Both Melanie Suki.

Numerous other patients who we have never talked about who our rating out there.

With each other and Facebook groups. They are very symptomatic, sometimes the word non advanced doesn't capture.

How much the patients are suffering.

If it is in drilling but there is nothing in Durant about this condition. These patients are truly debilitated the living bubbles.

So any symptom improvement is a big win and evaporate and have actually improved symptoms significantly more so improved the quality of life of these patients. So that is a big but you maintain enough. It says.

In addition to that the redemption of Tryptase burden mast cell burden and these are very important findings and it tells us that the drug is disease modifying its not just improving the symptoms on sites.

An additional point that you touched upon.

Previous slide was the use of other medications are polypharmacy that is a big point as well.

Other medications each one inch two blockers Bpi's chroma lane steroids Omalizumab and.

Many of our patients are in many of these medications, bringing down the burden.

A very important point, both from cost effect of those other additional medications, but also from the adverse event profile.

The other medications as well great.

Yeah, well I can just echo that and there is one additional point I mean, not only the patients also be as doctors wish you waiting for.

For such a drug treating.

Patients with systemic mastocytosis over the last 10 15 years was just frustrating.

Not only for the patients also for the doctors, because we gave them a lot of different drugs and none of them in many patients were actually able to really bring down the symptom burden y.

What we had available as maybe antihistamines is Luke Bryan antagonist trying to block whatever domestic mediators that are released from the mast cells in these patients.

Housing their symptoms, but we don't have a drug to block all the mediators stay is about more than 200, maybe it is that potentially a good course.

Symptoms in these patients and which is not surprising that even we gave five six different drugs for these patients it was not able to control the symptoms and many of them.

<unk> is one of the first in class drugs that now comes a bit earlier.

Not trying to block whatever comes out of the mast cells. It pre wins mast cells to released immediate areas of degrees as domestic burden in patients more or less it's really disease modifying and we haven't seen such an action of the drug before in mastocytosis.

And Dr. Wei I know you haven't used David hit before and you've only seen the pioneer data that everyone. In this room is theme. So what was impressive I think the two things one is the symptom reduction I mean, these people whether or not we treat them and as youll see we have patients with five six some of them, taking seven different medicines and as I'm want to.

They have brain fog and yet we give them drugs, because brain fog, which doesn't make much sense, but it's the only thing up till now that we have and the quality of life is much better base.

Based on the data and that really makes a difference for patients. These patients are unhappy.

Don't like their disease like they have to take a lot of medicine and more importantly, they don't like the fact that they came out of exist in society. The same way everybody else does.

When you participated in a number of.

Studies like this with Piero outcomes, what are your thoughts on the performance of the placebo arm as well every study I've ever done.

Done many okay, probably over 50 has a placebo effect.

Talk a lot about the placebo effect, but remember some patients magnify their symptoms a little bit so they get in the trial.

We have patients who would love to be in another trial and advocate so that means that when they tell us their symptoms are up here there actually here and then when we asked them they get better. So that's the placebo effect and then there's the anticipatory effect.

People don't know, which drug theyre getting these are all placebo controlled all appeals look alike.

Physicians don't know, which drug so and so there is the anticipation that I'm going to get better and so just the anticipation makes them better. This data is not at all surprising what would have been surprising if there is no placebo effect then we'd start to think about it great. Thank you.

So maybe we can go into the first case now so professor Stephen R.

Just turn this over to you.

Sure. So this is one example, one patient that was under trial. He was a young man who is a young man and he actually started early even in his childhood with being diagnosed with the allergic diseases allergic rhinitis and asthma you suffered from from his early childhood and then.

Over.

As a dollar since more and more symptoms started being border in him and then finally when it was 20 years old you get diagnosed with non advanced systemic mastocytosis in our in our center.

So he was carrying the <unk> mutation is tryptase was elevated not very high. So it was below 20, which means it doesn't count as a as a criteria for diagnosis, but anyways.

You said it doesn't reflect actually the burden of symptoms and is burden of symptoms with.

<unk> a lot so mainly you suffered from Gi symptoms that.

Made him to currently suffering from unpredictable diarrhea.

He was brain foggy also headaches she had a large his skin.

More and more that are covered by these bumps and lesions and he also suffered from bone pain and as you have heard before also this patient was on several drugs that was even more of a drive that him. He was here for a while and leukotriene antagonist, even add some short course.

Steroids, which can be given long term, but it was.

What's taken off because they were just not effective and not do anything else to him then <unk> already was taken he also wasn't cromwellian Angie.

<unk> is most patients because you also had the risk of NFL axis.

What was most.

Intuitive and this patient is dead. He was diagnosed very young and he was lucky enough. He told me once that's when he started his professional career he was actually able to work from home. He is working on it.

He was lucky to have like a company in Boston, we accepted as.

Disease influences and he said you know if I need to use the bathroom I can have my bathroom by the way.

<unk> and foggy I can't just laid down for an hour and then continue working.

When you started the trial even said it was.

Difficult to him to lead the severity of his symptoms because he was so used to them and maybe you can go to the next slide and look at his symptoms. So on the left hand side you see his total symptom scores divided by the different symptoms and you see that the spots on the skin.

Fatigue.

Was among the most annoying.

And also then in the Middle you see his disease specific quality of life measured body mastocytosis quality of life tool.

And do you see that many of US most visibly symptoms improved mainly the fatigue and also the gastrointestinal symptoms and this is much most reflected by the improvement of quality of life. So the black lines are the baseline and the Red line is actually how we improve over there.

A study of this is really significant.

As shown by the <unk>, which is a more generic and not disease specific quality of life measure too.

Yeah.

And last but not least ultra his spots and his skin lesions disappeared. This for US is a clear sign of the disease modifying effect. So.

Explained how these spot soccer understand so is the market of having increased numbers of mass sales on the skin. All these reddish boundaries spots is kind of a necessary to match those ships and you know we were trying in the past to treat the itch to treat the flush.

Even <unk> irradiated patients ages ago, but nothing was actually able to reduce the number of sports too.

Proof depict.

The picture and the symptoms of the skin and Ava, Okay. That's able to do this or does it vary.

Representative example of a patient in which we see just skin lesions paving over time, which is a clear.

It's really reflecting the reduction of the number of myself in this game.

Thanks.

And given our U developed BMC cure. So can you just comment on the depth of the quality of life changes that youre seeing and maybe put in perspective, yes, well I mean, if you had mentioned for the EFI for Judy.

We are not at zero all of US you know there is some.

Something in our lives did also.

It impacts our quality of life. So you cannot just industry zero, but this patient, particularly having improvement of over 50%.

Really a significant so if you translate it to the severity of impact it means you come from.

Very severe to mild actually so this is what the patients also tell US you know it's the first time in my life that I actually realized how impactful. This disease is for my life now we can go and meet my colleagues more often in person I can go with my friends and does this what clearly also dented the questionnaire reflects improvement of logical.

What you just said reminded me of a term that I heard from a couple of patients and providers, which is a new normal.

These patients have lived for a long time with what they consider normal but then when they were treated they feel even better than that and Dr. <unk>, China have you seen that in your experience in Africa.

Newly so.

Patients both before and after treatment so.

Prior to going on the treatment of pain.

<unk> have had this condition for many years and they get used to a new normal at that point, which is.

Far away from from what we would be.

They are living in homecare made many adaptations.

For example, <unk> just decided not to go outside.

That became her new normal.

That's not what we would want to be.

<unk> been some low grade symptoms like for example, diarrhea, which.

If any of US had one or two episodes of Scott you have you would probably not be able to be here because that could happen anytime so thats.

Prior to going on treatment and then after going on treatment patients improve and this is very heartening to see they reached a.

A much better new normal.

Yes.

And Dr. Wagner. This case does it seemed the cohort of patients that you are saying this is a very typical case I mean, the only thing maybe.

Not typical as the time it took to get diagnosed which is like all rare diseases. It takes a long time for these people to get diagnosed as I told.

<unk> told you we had one patient in whom I was the 72nd position that they saw.

And we finally were able to get her diagnosed.

He told me that yesterday, but how did you know there were 72 people before he actually came with her entire medical records about that high.

Brought in several boxes and said this is what I have done you have to find out what's the matter with me.

Alright.

Alright, so maybe we can move to the next case Dr. Rashani absolutely.

Absolutely I think you guys all saw the video but this is my patients suki, She's a 39 year old mother afford as you heard.

Those symptoms in her journey began in 2017.

But if you ask Curt actually maybe some of the skin lesions did even before that.

In 2017, she had the episode of Anaphylaxis that led to the ER visit encoding an ICU stay.

And she was eventually diagnose stuff non advanced SM in 2019, so almost two to three years. After her initial presentation, which by the way is also a shorter time period compared to the seven or eight years. Dr revenue was that afternoon.

And she was found to have the <unk> mutation, that's a classic mutations for systemic mastocytosis.

I tried.

Out of desperation.

Variety of medications.

Allergist Immunologist colleague tried Midas start NBA tried interferon IV for marketing.

And seven or eight other medications.

And maybe they had for a brief smile.

Maybe to help us set and symptoms, but the effects with just not matched to the point that was raised before by decade, but also by Frank before the Tryptase level. It doesn't really correlate much like the previous case. This patient has had a tryptase less than 20, but was not.

Nominally symptomatic right so her.

Baseline symptomatology included chronic diarrhea, sometimes six to eight times a day.

And when she would each I think food that would lead to pain and the Gi system.

Rainfall gross constant she was a featured before she had to quit because if all of these symptoms, but in particular brain Fargo was one of those.

We heightened from How're you correctly that she had numerous skin lesions erupting sometime around 2016 2017 trunk in your extremities were full of these very fine dots like the picture that was shown before she had bone pain.

Was bone pain, and some of our big bonds like the FEMA.

Long bonds are the hips and shoulders.

And recurrent anaphylactic episode this is a big issue for patients with SM, we didn't see this data.

The top line information from <unk> Pioneer study.

But you know these anaphylaxis episodes.

What really concern us as physicians non advanced SM may not tell you directly but an anaphylactic episode can take your life. So.

So she had numerous episodes to the point, where one day for example, when she was working in the school.

Some other.

Children's paintings, where bang perfumes, and she had anaphylaxis in the schools.

To quit working eventually.

And the Polypharmacy list is right there.

First one <unk>.

<unk> got <unk> and you can read through the long list, which also includes Omalizumab Xolair Epipen use 19, nine epipen injections can a year every time you inject that's it that's a nasty medication.

A lot of good medication, you don't want to use it as bad cardiovascular effects as well so.

The dark Blue Bar, you are reading that she stopped working she stopped traveling she would just not go outside their home.

Our only real exposures, which she was always very concerned about was visits to see me and then she would come I would make sure that none of my staff none of our patients.

We're even getting food items, which you are allergic to that they were not wearing perfumes that we were not using detergent due to clean up our office space because any of those could be triggers and DAYBREAK previous quarter.

As yet to isolate.

Covid pandemic absolutely didn't help.

<unk> as you heard.

He was unable to attend to your kids as events and multiple episodes of life tightening anaphylaxis.

Many of these could have taken her life.

As shown in the previous case here to what Youre seeing is that she was very symptomatic. So if you look at the total symptom score under last night with the symptom assessment form she was already symptomatic on many domains.

Fatigue brain fog, diarrhea, nausea, dizziness, abdominal pain headache, itching bone pain, and then what youre seeing in the Spider.

Spider plot is the debt, which is what the symptom improvement was on treatment.

Now the first question.

Some of my Fellows and residents asked me as well, but it has not gone completely it's still there.

It may be.

What this means is that now you are better. This is not a complete response, but this is a great response, which allows people to get back their life. They can start doing things that they were not doing before including for example, a trip to Selina.

Selina and Keith mentioned, a trip to Cambridge, Massachusetts, two weeks ago.

You may or may not know, but that was her first trip in years and years.

So she is able to do those things with some improvement right and then in the middle one.

We're seeing the mass so quality of life.

IMTT scores here too you are seeing some improvements.

<unk> fit with our story.

On the right side, you are seeing the EQ five D scores improve so on the blank richest the black bar shows higher baseline. She was far away from the U S. General population by 38% increase is a tremendous increase for a patient who was accustomed to living masonite entry.

Normal new normal life for her.

This was great and.

I don't know, if there's a future slate, but what put together.

<unk> she has been able to get rid of some of our medications.

You showed data, but cromolyn. So she has got downhill Cumberland use.

Xolair she doesn't need it as of a couple of months of being on Ava platinum.

She was on it for two to three years prior to that and it still wasn't working but now she is gone and herself off of that.

So talk about polypharmacy use going down.

<unk>.

Most important to me at least has been how she has been able to function banking society and now she is doing what I have always wanted to do which is applying for the job and get back to where you were before right.

I'm, Matt <unk> as well and tell me. If this is correct, but she described continuing to improve after that six month period. Yes. This this is a very important point so.

Maybe two or three months into her treatment course, we started talking about this earlier use going down and she felt like she didn't need it.

But her symptom scores and higher overall, feeling though was not fully there.

What really.

Interested me.

And she noted herself was maybe around six months to eight months into the treatment journey is when the brainfart lifted so she saw that by being on treatment for numerous number of months.

There was a seven point around six months or so when things improve so deeper responses can happen, sometimes despite being on treatment.

For a long period of time.

Professor Stephen or in your experience with advocate have you seen that improvement over time, yes, definitely I mean.

We have to consider that you know even if you are for six months on Ava presented.

Your muscles are not zero youll still have mast cells.

And depending on where you would start at baseline in house CPU symptoms are.

It takes time to improve and actually we see all of our patients improving over at the time of six months.

So it's a continuous.

Improve of symptoms.

But even that last longer than the six six months time.

A nicer study.

So Dr. Veterinary as we said you haven't participated in the trials and so I wanted to get a better sense of how your what your practice is like and where you see your patients from and what unmet need still exist in those patients. So let's talk a little bit about your practice so.

I'm in St. Louis and we have a rather large growing area. So I have patients who come see me from the eastern border of Indiana to the middle of Kansas.

Some drive down from as far north of Chicago and up from Northern Louisiana. So we have a very very broad.

Referral basis in our referrals come from.

A large number of other physicians some of them are other allergists, who simply don't want to deal with the problem. We see gastro neurologist for patients who have intractable gi problems that arent responding to the standard therapies.

Astro neurologists use we have dermatologists to refer them because they have spots.

And maybe Theres something in addition to the swaps the sponsor very troublesome for many of our patients.

And then we have neurologist because they see patients who say there must be something wrong I can't think this is the brain flung.

And then the last group of patients who.

Symptom complex, they consult doctor Google and.

And Dr. Google says, maybe you have muscle disease, and they come to see us for that reason.

The case to show how difficult it is to control symptoms with what's available, but before we go there.

What do you think of as the some of the most transformative newer medications that you've dealt with in the past say five to 10 years. So the idea of whats called precision medicine, you've heard a lot of talk about it.

And that is to try rather than treat symptoms, which is what we do up till recently with many of our diseases.

Want to treat the cause of the disease. So if you think about it we have biologics for the treatment of asthma brand new there used to be one of them another five and more on the way we have spot.

Medicines for our patients with immune deficiencies that we give them back what they are missing I treat a large group of patients with the disease called hereditary angioedema and we've gone from literally no medicine for these patients to three prophylactic medicines and for on demand medicines.

All of them looking at the pathways that caused the disease and interrupting that pathway. So I think the idea in modern medicine is what's wrong with the patient from a genetic.

Or biochemical.

Abnormality and how can we fix that by attacking what we know cause of the disease, rather than just treating a whole bunch of symptoms.

And I've heard from all of you that treating the actual cause of the disease is important in these new medications, sometimes we've heard.

Questions about access to medications like that so Dr. Linda what makes the difference in terms of getting access for patients.

We have a large number of people in our practice, who spend their time getting access, but having a program where.

All we have to do is send the patients information to a central access.

Registry and they get medicine, what's called a quick start program, you've already heard about it and which they can get medicine in a couple of days rather than in the old days, a couple of weeks or even longer makes a big difference because now patients have the anticipation they come to see is when you say you've got this new.

You Wonder drug that's going to fix your disease or at least make it a whole lot better when they want it now they don't want it three months from now so the kind of program that you guys have is really going to make a big difference in getting patients on medicine and keeping them on medicine.

Dr. Rick Honey in Alabama, what's been your experience with access.

Let me first talk about access to other medications and then about this winter access to other medications can sometimes be an issue you have to go through prior authorizations.

Dealing with many providers and it's just not an ideal way of dealing with.

A single patient with with many.

Arguing system environment.

In terms of access to Ava Peyton and we have not really had.

Issues.

Our non advanced or advanced systemic mastocytosis.

The social worker Keene pharmacy team has always been able to gain access whenever we have wanted to get access to the medication great. Good.

So Dr. Right now, let's look at your case and then.

I have a couple of questions. After that so this is a very typical case for us. It was a 41 year old woman, who is actually referred to us by the local emergency room, because she had an unprovoked anaphylaxis.

When she saw us that was the reason she was there but.

Okay history, she had frequent stomach upset she had years of aging and Flushing. She described how people would say why your face is really red what's the matter with you.

And she had occasional shortness of breath.

When we looked at Hershey had skin spots. She was flushing literally as you were sitting in the clinic setting.

She reported nausea, vomiting, frequent diarrhea, which he attributed to food allergy.

Which I can assure you she had none.

She did have a classic <unk> sign when we spoke the skin.

She had a chest X ray which demonstrated osteopenia. Her tryptase was elevated at 42, she did have the <unk> positivity.

You did have a bone marrow, which showed Matt Nelson.

Some unusual shape the spindle shape mast cells. This confirm the diagnosis. She started off with a few drugs, which didn't virtually no. Good and she ended up on this list with superior zine Famotidine and Montelukast that didn't work very well. So she was moved to Zeiss Lowe CR.

She is on <unk>, which is a very very sleep inducing drug she.

He takes gastro come four times, a day and she has epipen and she has a lot of them. So she has one that she keeps in her purse. She has one that she keeps at home. She has one that she keeps it relative houses just to make sure that theres always one available.

And so you can at the bottom you have persistent symptoms Oh, yes, he's still living with us she lives with it.

And she's one of the patients. She is very active in Chi every time. She comes in she wants to know when is this new medicine that she's going to make or better coming in.

And that soon or you have the.

<unk> unique training in that year, both the dermatology and allergology as they call them in Germany.

You heard about spots in all of these patients when you think about patients that come referred for cutaneous manifestations. How do you think about that with respect to overlap with patients that have more <unk>.

Related disease, or <unk>, I mean, our systemic disease.

How are those populations really yes, well I mean.

First is that when you look at the adult population most of the patients that are diagnosed within mastocytosis into skin actually have a systemic disease.

You just need to look at the.

15 years ago people were in sets.

They have a systemic diseases, what's kind of a you know non dangerous skin condition more or less might be a bit itchy then you'll take antihistamines and you will be fine but.

So it turned out patients on upside in how we do all the diagnostic workup.

In the other patients diagnosed with mastocytosis into skin and beside 90, 598% actually indolent systemic disease.

These patients and when you ask them. They also most of them.

The other symptoms.

Excuse me that couldn't be explained before it wasn't actually counted for symptoms of mastocytosis.

But as a dermatologist is actually very interesting to see because you know.

Many patients you know they come because of their skin not only but they come because of the skin and if you imagine yeah.

Young female young men are you in your teenage time.

You know in your early twenties and you are covered by these thoughts and nothing helped before we weren't able to target. These spots at all and advocate is the first drug that is able to do this right and.

And Dr. Wagner you described some of your patients coming from Dermatologists and I think your point was that they ask about the skin and don't go beyond that correct.

Intelligence look at skin.

Definitely it doesn't go away.

Okay.

But when you take a history, what Frank said is absolutely correct all of a sudden you know.

But they have attributed a lot of their symptoms does something else its not unusual for them to say well, yes, I came because they have spots, but I also have allergies, the foods and that's why I have Gi symptoms and I flush cause I ate tomatoes.

So when you put it all together the vast majority of these patients have systemic master cell disease.

And Thats, what we have to treat it just can't treat the skin because they just don't get any better and when you think about the spectrum of patients that you see how do you bucket them in two patients that would need a treatment.

The benefit well a lot of them do if you think about those as Frank said a lot of our patients they have spots in the spots are getting worse.

Women in particular will ask me these spots going again in my face and we say well I can't guarantee or not but anything that could target. The mass cell itself Nomura. We know what causes the spots. We know why they are there anything that would actually target the mass cell is going to make.

Youre going to get a lot of people who would be willing to take this drug simply because you can see it's probably going to make your spots better. The fact that it's going to totally change. The symptom complex you have seen that now quality of life gets better symptoms get better we're going to have a lot of patients who are going to be up to us.

Advocate as a primary way of treating their disease.

So.

That's the kind of the Chinese what would you say to somebody who would argue that most patients are well served by available medications in this disease.

While they are not [laughter].

Anyone who has seen.

Even a few non advanced systemic mastocytosis patients will know that they are not well served.

Still ready symptomatic on numerous medications and adding toxicities of stores other medications be that drowsiness, b that the ugly taste and sometimes even daria from Cromwell and let's say.

The steroids, causing their own numerous other issues.

And to me what this Doug elaborate and re presence is.

One one <unk> with multiple targets in many ways you are controlling a wide variety of organ systems are multiple symptoms with a single treatment.

Well. Thank you all for your presentations.

We're going to open it up for questions for the clinicians and just a second but before we do that I just want to remind you. The things today that just to remember first of all this is a devastating disease I hope youre convinced of that now secondly, Eva kit makes a huge difference for these patients than it does so by targeting the disease and that the more day.

We look at the more into focus the profound dramatic benefit for patients comes into focus so let's open it up for questions for the clinicians.

We will have a more general Q&A session for the rest of the company later, but are there any questions out there for the and if you could please identify yourself and your affiliation.

Got a microphone coming around selling.

Alright, Jeremy.

Jimmy you got.

No.

Just a quick question for the clinicians are there any.

<unk> towards our referring physicians to use depending on severity of symptoms. So we see from the prior slides.

Oncologists visits Gi diseases, et cetera, et cetera, the more severe patients come to you.

Referred to by Gi Doctor or oncologist or yes.

Help us out with that.

Yeah.

Right now if you were to ask me I think a vast majority of my patients come from Allergist immunologist and all her dermatologist.

But.

We have seen patients from gastroenterologists already been pulmonologists.

Once a neurologist because how many neurocognitive issue but.

But I would say allergy immunology and dermatology are the two primary big practices from there to come.

Hi, Brett from Stifel. Thanks for taking the question over here.

For the pioneer investigators you discussed the reasons for the placebo effect, but I want to ask for any of the patients you had on placebo on the trial can you characterize the impact from Eva keeping patients rolled onto drug at the end of the study and then I have a follow up.

Well.

I think what is quite good and the study design of pioneer is that all of the patients in the edge rolled over to a real.

Drug treatment and you see we have seen this placebo effects in the very first weeks, which resembles what we think placebo effect is you know your attempts to raise yourself a bit worse to go into the trial and then you rate yourself a bit better because you hope you on drug but dessert.

Something which fades out Oh, it's out of the first couple of weeks and then you have these plateaus.

On placebo, but you have a continuous improvement.

On symptoms and quality of life on the patients that are on a drug and you also see this when it comes to the rollover than the placebo patients come in.

<unk> also come down to the same level of symptom improvement than the patients that have been already addressed before.

So I wanted to ask in terms of the clinical meaningfulness. If you look at the clinical benefit of <unk> on the basis of its absolute benefit which was about 15 points and symptom reduction or on the placebo adjusted basis, which was about six points.

Well I mean, we actually do this on statistics are the placebo corrected way.

But I think what turned out to even is that the disease.

Is more than we can capture is actually not an easy to capture disease. You know there's many many different symptoms and we have talked a lot of anaphylaxis for example, or osteoporosis with just not even captured by the symptom scores. It may be captured by the quality of life, which is a more you know look at how the patient is doing and <unk>.

<unk>.

But since there's not one single symptom that applies to all you know, it's very heterogeneous disease. When it comes to the symptomatology and therefore, the real improvement is even harder I would say one of the hardest diseases to capture in the setting of our clinical trials because all patients are more or less different right. So this is why we are.

Also look at the total improvement right because we know that there are things not very well captured by the by the bureaus, we have to use.

I just wanted to add two points due to the effects of viewpoints.

Patients don't care about the specific time point at of the primary endpoint for clinical trials.

So the $15 16 points that you referenced it in reality, it's more like 20 points for them with deeper treatment courses as we saw in the pioneer study. That's one and then the other thing I would add to it is that.

These mean symptom score reductions don't capture the entire story.

As an example.

Let's see if there was a patient who is.

With them.

A big burden of symptoms, but.

<unk> issued a one big symptom that is affecting them is let's just say the Gi symptoms.

<unk> been in the abdomen and diarrhea, instead alone improves that can make them more functional and have an improvement in quality of life. They may not necessarily have to have symptom burden improvement across all of the domains. So that single number of mean total symptom score it doesn't capture what happens for every individual patients.

Yes.

And maybe to add don't forget that these were all patients being on polypharmacy before nothing we're able to change or improve the symptoms and then what we see with average it is actually what what comes on top you know there's nothing we can compare this with but this is an improvement of symptoms.

Two patients that are taking six seven different drugs and nothing was able to improve them.

Some of them Richter Goldman Sachs.

<unk> segment of this market into three groups and the advances to them and then the non advanced september's severe and moderate can you just help us understand who the adopters of the drug or within these patient populations and what has played out so far with advanced SM at the bottleneck primarily been <unk>.

<unk> just given the heterogeneity and how do you think this might improve over time.

Maybe let's start with the question about advanced SM and death of the Chinese Hematologist.

If you remember the drug <unk> has been FDA approved for advanced SM only since June 2021, So it's what 14 months right now 14, 13 14 months.

So many of the community physicians are.

Now more aware about the drug as compared to maybe even six months ago.

That's one.

Other issue the other point that I want to address that.

There is far more a very nice about advanced SM and SME agenda.

Advanced SM has three subtypes of advanced SM.

So the field as a whole is learning more about these subtypes of advanced SM.

And that is a learning curve that I believe we have been through at this point.

Now in terms of treatment adoption as whats the point product before should we be treating systemic mastocytosis first are the advanced hematologic neoplasm, which is the biggest subgroup of the advanced systemic mastocytosis.

And then just one.

Good treatment options.

As with <unk> based on the explorer and Pathfinder studies.

We have also line.

The secret mutation is a multi lineage, which means it's found in both the mastocytosis.

Component of advanced SM as far as the other hematologic neoplasm component.

With this knowledge and now with more awareness about <unk> as well as advanced SM, we are seeing more and more uptake in the community for the use of <unk>. It is.

The undoubted.

Treatment of choice for patients with advanced SM.

And before we get into the non advanced I think it's important to remember that we had a lot of patients with.

SMA on the study patients.

Patients, where the <unk> component will improve as well.

That part of the uptake is a bit more labor intensive than the patients that have the pure advanced SM and so we do expect to make inroads both showing data that we generated and the Pathfinder explorer studies as well as looking at combinations in that area to address both diseases at the same time in the future.

In terms of the types of patients I guess is your question that in mild moderate and severe there'll be early adopters what are you.

Well I think.

Our advanced patients, we always treat in collaboration with our Hematologists oncologists.

The ones that are not advanced largely taken care of by Allergist Immunologist and I think that the uptake for if the drug is approved for the non advanced will be in the allergy and immunology community. We're very tuned to this is a disease and <unk>.

We're looking for better treatments for this group of patients. So I think you will get a lot of uptake once the drug is available.

The weather in the past you said to me that some people think of a new drug is being first given to the most severe patients, but I think you have a different approach no I don't think that's true I think there is a little bit of hesitancy about the ones that are most severe I wonder if theyre going to get better, but the ones that are the mild moderate or.

The ones I think where you're going to see a lot of use of this drug because you have a better chance of it working.

And as physicians, we want our patients to get better. So when you see a patient you really certain that you have this new drug they are probably going to get better theres going to be a lot of uptake there and then we'll move to the more severe patients because we will learn how to use the drug will learn that it is a very safe drug remember are more severe patients.

Have more symptoms so side effects would be more important.

Think that the uptake will actually be in the moderate group and then it will progress toward the more severe but non advanced systemic mastocytosis.

Yes.

Maybe what I'm going to ask completely correct, what you say the field of Allergists and Immunologists they were actually well prepared for this drug.

Most of diseases is between our.

Matt So driven domestic mediated.

<unk> awareness and.

Knowledge about what the drug is adding to the field is very well perceived Indiana communities.

Thank you have a question over here.

Thanks, Ren Benjamin JMP Securities can you talk a little bit about whether you see a complete resolution of polypharmacy the longer patients stay on therapy or is there just a new level of polypharmacy that you see and when youre looking at patients.

Especially easily called newly diagnosed patients do you put them right away on something like Eva or do you try polypharmacy first see if you can get it.

Joel and then eventually move to Dave.

So well.

From my standpoint.

Fact that you see from the pioneer data these patients are getting better or many of them actually on their own patients don't like to take medicine. The human animal is not a really good medicine taker.

So they will on their own start decreasing their medicine, and I think you see that I don't need my Omalizumab anymore, So I'm not going to come in and give my shot.

So I think that one of the things that will happen as a result of a targeted therapy will that individuals will stop taking their medicine.

We will work with them as allergists and how to stop taking them, particularly some of them you don't want to stop you know cold, Turkey, if theyre on let's say steroids, that's not a good idea, but I think one of your you're going to see is the fact that they don't need them means they will stop taking them.

I think it's important to remember that we do.

They often tried not to stop in the first six months and we will.

Is that more comprehensive data about the long term polypharmacy overtime, but with respect to your management of a patient that comes in newly diagnosed.

Professor Stephen or what are your thoughts about either optimizing well I think you know I think the situation will adopt to the management of other message driven diseases. We did before for example, chronic urticaria, we have a treatment algorithm.

International guidelines and of course, we always start with the antihistamines, because the availability of cheap and they're helping some patients in all.

But the vast majority of severely affected patients they will not help them immediately.

It's something you realized very quickly and then it's the points to go to the more advanced treatment options.

As we are expert for the disease, we see most of the severe patients. So I think our decisions will be very quickly and we have to experience that you had the estimates and other drugs doesn't work well. So we do the first drop but it just doesn't work we will come with the second shot rides right after that.

Also as our physicians we don't.

We don't really like to send our patients to four different specialists, where management. That's just a lot of burden on the health care system patients.

Ben to enforce specialist multiple medications medications at very high doses compared to what's usually Kevin.

Not just polypharmacy.

I much like what was mentioned before I see adoption.

Adoption.

Early phase in a patient's journey rather than using it after numerous other medications and what are the patients opinions about about whether they want to try other medications that they're interested in something that hits their disease.

But they definitely want this becker.

Welcome you to come to the UAV MTN clinic. After the pioneer study completed enrollment I still had patients who wanted to go on they are eagerly waiting to either get the drug once its FDA approved argon blueprints other clinical trials, which we can I'm sure that he will talk later.

Other questions.

Yes.

Yes.

Ice Kings wind investments.

It sounds like.

Diagnosis of the disease can take many years can you comment on.

We made typically see and do you think that now that there is a treatment that.

The timeframe to diagnose correctly.

Yeah well.

This is not unique to mass cytosis, it's unique to rare diseases.

For most rare diseases, the time from onset of symptoms to diagnosis is about nine years.

<unk>.

The hope is that as you have better and better therapies, one of the things that I, often say is nobody's going to ever make a diagnosis. They don't think of.

So the hope is that we will interact with the community with the physicians that we deal with and make their awareness of this disease greater so that we can shrink the amount of time from the onset of diagnosed symptoms.

Symptoms to the diagnosis.

Maybe to add to this I think this is even about to change, but we have learned so much more about the disease in the last 10 15 years and the experience we have now patients telling us. It took nine years to like a diagnosis is patients that are having the disease already 30 or 40 years, so at that time.

It was what it was.

But there was so much awareness about this disease in the last 10 years.

This mastocytosis.

As in the head of every allergist or dermatologist or even other doctors so I think.

Nowadays, even so it hasnt been catch up catch up to capture sorry body by numbers, but I think nowadays.

The disease is diagnosed much much more.

Yeah, great well. Thank you all for your time.

Thank you.

Thanks for your participation.

Trials and.

Your many years of knowledge about allergy.

Thank you.

We will take a short break right now about 10 minutes and then we'll come back with the next part of it.

Presentation.

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Sure.

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[noise] may I have your attention. Please the meeting will begin in five minutes. Please take your seats.

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[noise] the meeting is about to begin as a courtesy to the speakers and those around you. Please silence all devices.

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[noise]. Please take your seats in silence your devices the meeting is starting.

Now thank you.

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Yes.

Please welcome to the stage President of research and development Foulard pneumonia.

Hello, everyone as you heard from the voice of God, Amazon and then when you're president of R&D at Blueprint Medicine.

Two years with blueprint medicine, and I wish that with you today my perspective on our R&D.

And how our R&D is going to achieve the vision that Kate Haviland, our CEO shared with us for 2027.

I will also give us an update on our Egfr 94, five and all of the Egfr pipeline data and how are we setting the strategy for this.

<unk> really addressed a high medical need.

For this very complex disease.

I will invite Dr.

So firstly caused our chief scientific officer to come and take us through a full resource updates, including our new platform of targeted protein degradation and how at the blueprint we are using our expertise in this field to leapfrog. These new envision your technologies.

With two approved medicines in multiple indications with 14 development candidates with a high success rate from IND to POC and we'd five breakthrough therapy designation by the FDA blueprint.

As published a robust and productive.

Andy capability.

But the most important question I ask myself over the last two years why is that what are the drivers for such a robust and productive R&D capability.

And it was able to identify four key things.

One is the scientific rigor.

And the scientific decision, making that's what the teams have blueprint.

Number two is the focus on precision medicine.

And build a platform that is designed to give highly selective and yet potent.

Tyrosine kinase inhibitor with a discipline to look at target product profiles, but achieve high bars and stick to them or replace them through our.

Our platform.

Number three is our highly experienced research and development teams.

They are not only highly experienced within the research and development. They have been asking over the last many years as talent magnet I witnessed personally during the very difficult period of our industry. During COVID-19, how tough it was to be able to attract tenants and the team's up blueprint yet continue to do that on a regular and consistent basis.

The fourth one very important one is an efficient management of resources and accompany our age and our stage. It is important that we allocate our resources and finances, the right way, where we think we can make the difference and be very very much focused.

We continue to focus on high medical need diseases.

Now we are moving to doing it in more and more patients with scale in mind to help even a broader population of patients.

Few key things I would like to highlight on this slide.

Building on our kitchen mutation experience that you heard about earlier from a number of presenters, including neither an expert in the field of systemic mastocytosis, we are expanding our reserve to wild type kit to address.

In the space of allergy, some very important challenges such as chronic spontaneous urticaria.

We are building on our experience in lung cancer with the governor of Idaho.

To use our pipeline of agents and address the complex challenge of the resistance Egfr driven lung cancer.

In breast cancer in hormone positive breast cancer, we are focusing on one of the most exciting approaches targeting CDK too.

And we are also looking at CDK to outside of breast cancer in C. N E. One amplified tumors in the Gyn's spaceflight endometrial cancer and ovarian cancer.

In addition to our collaboration with Roche on immuno oncology.

<unk> will update us on where we are there. Our teams are studying multiple undisclosed and resource program covering a variety of targets on a variety of areas in medical with medical need.

How are.

Are we continuing to scale, our R&D and how are we continuing to prepare us for the 2027 high bar goals that we will be able to achieve.

In terms of platform and in support of our tires and kinase inhibitor platform that continue to give and gave highly.

Highly selective agents very important agents for geared towards the use of single agents or even with combinations with other agents.

We are adding targeted the traditional platform. So I mean does it go edition platform is a very crowded area. A lot of people are interested in this new approach to really drug very important targets 30 cover later on will show was how blueprint building on our experience. We think we can leapfrog the feed in this space.

We are using more and more translational data as they would take us from the Egfr experience as an example to really help us makes scientific or sinus driven decision to help us exited the cycle of development of our pipeline and to help us bring precision medicine to the right patients very quickly.

Our culture of innovation is key to us.

It is important that we continue our scientific rigor and depth and anything that we do.

The urgency to patients we'll see how we are moving fast with our Egfr and other program has been key to us and will continue to be I heard this morning from the prisoners.

Via diseases, whether it's oncology or hematology or rare diseases associated with patients who do not wait.

Okay.

Last but not the least.

As a company with our age and our size.

It is important for us to really use our resources in the most efficient way make some choices, sometimes some tough choices, but be scientifically scientifically driven be focusing and go for where is our highest ability to impact and to win for patients.

Let me move gears to update on where we are on Egfr look at the overall medical need area, where we think our pipeline can impact and set the direction for our Egfr molecule. So we know where what are we.

Focusing on moving forward.

Okay.

It goes it goes without saying that lung cancer is a devastating and deadly disease and with all the progress have been made over the years. Many many many patients continue unfortunately to die of the disease.

In the gym Viva space Egfr is the most frequent driver in this disease with about 60000 patients worldwide coming every year to first line therapies.

For statin therapies.

Regardless of the progress that was made in the first line space.

Egfr is not is it still a high medical need disease. There are two activating mutations driving the egfr as it is one in the eight and 858 are activating mutation for simplicity I wouldn't call. It L are during.

During the presentation and the other one is exon 19 deletion.

Regardless of the progress that we have seen an $8 eight hour alloy continuous to be high need in this space of Egfr driven not smaller.

Non small cell lung cancer.

At Blueprint, we are using our pipeline to address this complex and high end met need situation with a pipeline that is billed as a complement to complement complementary and synergistic pipeline, but also as you heard this morning, as a module or a pipeline with a number of medicines or number of molecules that could become impact.

<unk> medicines.

Regardless of the progress that was made with us emerging as a third generation <unk> in the treatment of non small cell lung cancer driven by Egfr. There are still a number of issues that we see and we will continue to see over time.

So do we key ones are first one the benefits in the L. R activating mutation population.

We continue to see a lack of benefit or a lower benefit in the LR population compared to the exon 19 division probably due to an incomplete inhibition of Egfr activating.

Activating mutation by the third generation tyrosine kinase inhibitors.

I wanted to treatment.

Continue with tyrosine kinase inhibitor, we do see more and more.

Resistance mutation emerging over time, driving the resistance in the Egfr crohn's or part of the disease.

Therefore, we believe at blueprint and working with our investigator that the most important thing.

Not to go I'm faced these mutations this additional information in the very late stage in a complex and heterogeneous disease, but it will go very early on in the treatment and try to prevent the emergence of these clubs.

In addition to the Egfr resistance there is what we call off target resistance and a number of driver genes as you see on the slides will be driving the resistance in the late stage population of patients and when I talk about late stage I mean second line and beyond which you don't see a lot of it in the first.

And setting of Egfr, driven non small cell lung cancer.

Let me zoom in here on what we learned from the <unk> experience in the 858, <unk> activating mutation or LR.

Clearly from the us emerging a registrational study in first line non small loss in non small cell lung cancer.

<unk> with <unk> activating mutations have a much lower benefit than patients with exon 19 dealers and have an activating mutation would a difference of more than six months and PFS being shorter on alloy compared to exon 19 edition and in fact.

Patients with <unk> have one year short our median overall survival compared to patients with the other activating mutation exon 19 division.

Data suggest that in incomplete inhibition that third generation kick <expletive> is probably behind this as you can see in two San line models, comparing exon 19, deletion and 858 off where we can see a full inhibition on exon 19 on the right side.

The slides and an incomplete inhibition with at all.

At blueprint, we develop our pipeline.

From our productive.

Okay.

Platform to address the complexity of Egfr.

Mutations.

It was through what we have been developing at blueprint blueline four five.

Has been designed to focus on the driver mutation and in particular with the high potency.

As an activating mutation to.

To also cover two resistance mutation <unk> hundred 90 M to third generation Teekay eyes, and to first generation <unk> and <unk> 7 million seven S. Two third generation to gas.

Importantly, this agent has also been designed as the best in class in terms of selectivity over wild type Egfr below 945, a selective almost 900 falls over a wild type Egfr in biochem and experiment and is more than 500.

Paul selective over Egfr wild type in seller experiments.

Blu 701, and its backup Blu 525 have been double up for full potency on the driver mutation or the activating mutation, but also a strong potency on the resistance mutation to third generation <unk> the <unk> mutation.

More importantly, it's probably the best in class strategy in terms of brain or CNS penetration as you have described it in the past so highly brain penetrant agent.

For example, 20 insertions, we have set the bar at the blueprint at a very high level and remember I just said when we go through our <unk> platform. We said profiles, we set the bar high and although we can make them or we try to find something that corresponds to the high bar we set two.

Our research team set.

We're looking for four criteria oral agents.

Covering measure insertions of exon 20 selectivity over wild type Egfr.

And solid CNS penetration of brain penetration.

Through the acquisition of language Therapeutics earlier. This year, we have been able to identify blue has become blue for five one that in the preclinical data fulfill all the criteria. We have described in our TPP and I'm happy to share with you also in addition to 94 five data some blue for five one very early signal.

From the ongoing concern to phase one.

So before we go to the 945 data from the Phase one trial Symphony.

I would like us to look at what are our key takeaways and how are we using the monotherapy data the preclinical data and the early observations from the combination data to really guide our strategy and how to help this population of non small cell lung cancer with <unk>.

As an activating mutation.

What do we have seen with Blue 94, five data is a very low adverse events in time is related to wild type Egfr.

We have seen in terms of activity a major decrease in fact, I will be able to show your clearance of Cte DNA in the majority of patients with a variety of mutations.

We have seen clinical responses and clinical activity.

Blow 94 five.

Clinical activity was not durable as we have been dose escalating in the late stage patients sort of line four lines of therapy, sometimes all the way to six or seven lines. These patients had the egfr component, but they also had bypass mechanism as you would expect and therefore their GFR responses are not durable in time.

But that would give us enough confidence and the proof of concept for what Blue line four five as a single agent is doing.

We talked about the medical need in Egfr LR. We also talked about the first line Egfr lung cancer that is different from all the other lines in terms of Egfr being the major driver of the disease and.

In regenerate and some preclinical data that showed that the combination of <unk> and blue 95, not only.

Improving the.

Or blocking tumor growth, but also in preclinical models improve survival versus each single agents.

We are not seeing.

And major impact of Egfr Wild type adverse events. In fact, we are seeing low egfr adverse events from the early cohort a combination of <unk> and about 945, and we believe because of the all of these aspects that in order to help patients in the most efficient way as soon as we have a recommended phase II dose.

As for the combination is to move right way to look at patients in first line with <unk> is an activating mutation.

This is the first time, we presented data on Blu 945 from our B cohort monotherapy.

These data will obviously be fully presented at describe it at a major oncology conference.

But let's let me update you on what we have been seeing in this dose escalation.

Steady.

Blue 94, five was generally well tolerated with very limited Egfr wild type related toxicity or adverse events.

We have reported some dlt's through the dose escalation process, but all the DLT is we're not wild type Egfr related in fact, we have seen as you would expect with Teekay LNG elevations fatigue, nausea and vomiting.

Now when we look at the activity data.

There we can see on the left side of this slide amazing level of clearance of Cte DNA and remember these are very late stage patients with multiple mutations. This subsidy DNA will seen in L. A C S. Regardless.

Carlos of T M b with or without you and we have seen also some triple mutation patients with exon 19, Dell as a driver and so on.

This.

Major clearance of Cte DNA in these late stage patients.

So it was match it with the clinical activity.

In the majority of patients in this population of patients, including two partial responses.

In this very late stage heavily pretreated population of patients.

As I mentioned the four.

Of targets and the reason is the durability of response was not long.

But that does not really hinder the fact that the.

The full inhibition that 945 is doing this at the late stage.

Is one of the.

<unk> belief system, we have in terms of taking it in combination to the first line.

Bypass resistance of off target resistance in late stage, Egfr, driven non small cell lung cancer.

At baseline for patients when they entered the Blue 94, five we have been able to see the majority of patients consistently a number of drivers are listed all here. They may not come as a surprise in terms of a driver because we knew we were going to happen we're going to see some of these drivers in the P. M.

We not only see them a baseline.

But many patients had them also had additional bypass or off target driver of her disease.

And offset a P.

In fact 27, 24% of patients had multiple drivers at the same time.

You're just telling us that egfr driven.

Lung cancer is a very heterogeneous disease in more we go two late stage patients. The more we see other things that are not related to egfr.

And therefore in order to prevent the disease progression.

We need a robust egfr inhibition.

As early as in the frontline setting or in treatment naive patients before all these after August region started multiplying and appearing.

Now that we set the direction for 94 five in its combination with North American Ed.

Now we have set the direction.

Based on the totality of the data from the monotherapy that was not enough. We have said this direction also based on preclinical data and what we're learning from the combination in first line in combination in lung cancer.

The unique profile of 945, it was build with high level of selectivity allows a high level of inhibition of all the mutation LR. She S T M or <unk> or even LR as an activating mutation in a way that is much higher than what we see with first generation defeated.

Our third generation was emerging from the biochem data on the left side of the slide.

It is interesting to see over time, when the third generation Teekay as have been double there was really a shift.

This selectivity profile to be more selective and more potent on the exon 19 division compared to the population of patients where blue line for five we'll have to play an important role.

This is another element that is making us think that putting them together automotive in line four five could.

Achieved full inhibition of L. R.

Most recently actually last week at the <unk>, what you see NCI ACR or Triple meeting in Europe . Our teams were able to show some new <unk>.

Preclinical data focusing on al are in treatment naive.

Patient derived xenograft, where looking at tumor growth in this representative.

Pdx for the disease, we're targeting I mean, we're looking at monotherapy <unk> nine four or five we're looking at single agent <unk> and the combination of both and you can see a strong additivity overtime for the combination versus each single agent.

In terms of controlling the tumor growth in these pdx model.

On the right side, we have also seen an improvement or increase in overall survival in this preclinical experiments of the combination of <unk>.

And life grew 94, 5% compared to each single agents.

Yes.

So where are we from.

Our early.

Symphony trial dose escalation for Blu 945 and also emerging.

So this was started the dose escalation back this past summer our teams have been really moving with speed and efficiency.

Fully recruited two cohorts for the combinations in acuity two cohorts NBA D and just open the 400 milligram cohort in Q D for.

For the combinations of Biosimilar Enbrel and four five.

First well see most of it is used at its approved dose of 80 milligram.

Second the population of patients we are looking at and this is really more geared towards those escalating looking at safety and getting a recommended phase II dose and these are late stage patients.

We are allowing patients to answer this dose escalation with they have to add one more pricy guy, but I can tell you that many patients had a number of lines of therapy coming to this dose escalation.

We're happy with the progress of this dose escalation, we are seeing minimal evidence of wild type Egfr related toxicity, we have not reported dlp's to date and our goal is to continue this work to get to a recommended phase II dose and on the right.

Way expand in our target population of patients, which is the egfr non.

Non small cell lung cancer.

So overall I think the totality of the data from monotherapy from what we are learning in terms of safety of the combination continuing the dose escalation from preclinical data what this biochemical sell our preclinical pharmacology models.

Is telling us that they need in the <unk> hundred eight our population of patients in first line non small cell lung cancer.

It can be addressed with the combination of 94, 5% and also emerging.

Now that I'm finished with 945, let's move gears to our plans for the 525 back up to 701.

The phase one harmony, which is a dose escalation trial looking at 701.

Ascribing earlier has been through those escalation for four cohorts. Two included two NBA D with early signs of clinical activity and translational activities through CD DNA.

The metabolism pathway did not allow an increase of the dose to a level, where we think was our projected doses from the preclinical work that we have been doing well.

But have been watching this the team has advanced the backup 525 that person will take us really through the detailed profile of 500 to five on one side by side with 701. This backup use a different metabolism pathway.

As similar or strong potency on the activating mutations and the resistance mutation.

Has an improving selectivity profile and has also an improving brain penetration so call. It a backup but the more I look at the data the more I think this was probably nextgen or potential of best in class agents as you will see from that.

Today's presentation.

<unk> is to start the phase one and $5 five in the first quarter of 2023 and it has to be very clear that patients who are benefiting from 701 now in the phase one trial, obviously will continue.

This investigator decisions as we would be winding now winding down the 701 trial.

The third part of our Egfr.

Synergistic and yet modular pipeline.

Is blue 451.

Just to remember the acquisition of language Therapeutics was finalized at the beginning of this year and this phase one study named.

Named concern you saw that at the end of the first quarter. This year. This is one of the fastest.

<unk>.

Lung cancer or in oncology I have personally experienced it.

We started the dose escalation at 200 milligram at the 100 milligram excuse me and we are now at the dose of 400 milligram.

No DMT have been reported so far with Blu 451.

And no treatment related grade three or more adverse events have been reported to date.

We started seeing some activity and we are seeing responses at different dose cohorts of the escalation continue as we also started seeing some brain our CNS activity with this agent.

But I chose to share with you. This particular patient case, given how have any preceding these patients and have and this patient now is five cycle in the treatment.

This is a 63 year old female with exon 20 insertion is non small cell lung cancer.

Who had three lines of therapy. The first line of therapy was the combination of <unk> and chemotherapy.

That was discontinued for progression of progressive disease. The second line was C. N N zero as one that was discontinued for toxicity reason.

And the third line therapy was <unk> 189 discontinued for progressive disease.

The patients entered the study at the second dose cohort of 200 milligram and the only related as she had was a great one.

<unk>, which is a wild type egfr related.

With a decrease of 58% and is targeted isn't and you can see on this.

On the scan how large was the tumor of 88 by 40 main limiter on the left side.

Shrinking almost by 60% in size on the right side.

At cycle too.

This is one of the most rapid responses you see when you treat patients in oncology, where it's in the first scan that you see this progression.

More data from this study will full data will be presented next year. This is an early signal. It is very encouraging and this is why I chose to share. This patient's case with you. So when we look at the totality of what we have been doing in the Egfr space to address a very calm.

Flex very complex.

Very heterogeneous disease.

Sure.

We focused our.

Blue line for five and also emerging combination development on the highest need in first line and that's why we believe we can impact based on the AWS.

What I said from the R&D strength of a blueprint over the last many years and to continue is.

Use the data use the translational data use the clinical data and follow the science and made some strategic choices, where we believe the impact will be the most important in patients.

That's a 94 five story.

Blu five to five.

Clearly is.

Data driven choices and this is not from a PK once we learned on 701, but more importantly, it's a speed story.

Urgency to patient this had been developed with a very short period of time to probably become a best in class.

First I will describe it.

And we can see when I say speed the story even with this.

Replacement and moving with 502 five the impact on the overall timeline is minimal.

Lastly, it is really.

For Blu 451 is setting a target profile from what we learned from our library and put the high bar for the target profile and stick to it.

And it.

It was not available to blueprint in house, we were able to find it outside this comprehensive and modular pipeline will help us address the most difficult to questions in the Egfr driven non small cell lung cancer.

And to the earlier question around do we have a winning approach do we have a solid approach to address egfr.

Driven non small cell lung cancer.

The answer is yes, we do.

I want to thank you and invite thirsty Carter, our CFO to take us through the research update.

Alright, well, thank you for a lot and good morning.

When we think about research innovation at scale, a blueprint it begins with our talent and therefore, it's my privilege to present, you our science leadership team.

These eight individuals each have deep expertise in the basic science that underpins modern drug discovery.

In addition, each of them has extensive experience in the applied and translational sciences that underpin science led non clinical development.

So collectively they represent an expert group of collaborators for our colleagues in clinical development and an extra group of leaders for our colleagues and research.

And it is indeed this collective research team bench.

Bench scientists computational scientists experimental planners experienced program leaders, who work together to take advantage of our two integrated platforms.

And literally create the next generation of precision medicines at blueprint.

When we consider our portfolio, we think about both VR and the D. Together.

And so indeed, when we think about new opportunities, we begin with our knowledge.

All of our development programs what are we learning the clinic what opportunities do we see what have our colleagues from commercial informed us about is they've learned more about the needs of the patient population.

And so we take that knowledge and big dealer and ask first the question is there another molecule that we can bring in to one of our existing therapeutic areas that will help us provide still more patient benefit.

And then of course as you might expect we're also very happy to.

Do you think about new program opportunities, New science that can lead in the future to the creation of new therapeutic areas.

Recently, you have heard us speak about externally partnered programs on the lower right hand portion of this slide and this is something that we've done not only recently, but also historically.

And what this entails is taking molecules from our research engine and partnering them for clinical development with other colleagues in the industry biotechnology companies pharmaceutical companies.

In the past 12 months, we've reported on two new buy side transactions highlighted on the top portion of this slide.

That is to say collaborating across research and development with our colleagues and business development to bring in new molecules to the portfolio.

One very dramatic example is the one that <unk> just highlighted for you the acquisition of <unk> therapeutics, leading to the introduction of Blue for a five one into our non small cell lung cancer portfolio for Egfr mutations.

A more recent example, we announced in February which is to say our collaboration with Protium at advanced AI for purposes of protein degradation and I'll talk to you more about that later on.

Before jumping to the science, let's think about how we view the overall portfolio from a research perspective, and what I would highlight for you as a focused approach that begins with these four criteria can the project lead to a transformative medicine does the project have a patient selection methodology do we.

Do we have defined decision points both of the early stage and projected for late stage and then lastly, and critically do we have an edge does blueprint have the ability to apply its focused small molecule drug discovery platform to the project. If we can answer all four of those questions in the affirmative than we are.

Received but of course, we're constantly checking in on these questions even as the project progresses to make sure that we're still allocating our resources behind what we believe will be projects that produce medicines that matter for patients.

Okay.

So today's update I'll cover five topics too from our development portfolio, our Egfr backup candidate and our CDK to program. I'll, then turn to our research portfolio, where I'm pleased to talk about our wild type kit program and provide a brief update on our immuno oncology collaboration with Roche and then we will come through the presentation and at the end.

With a brief summary of our recent efforts on targeted protein degradation, so let's jump to the science.

Our Egfr portfolio has the potential to address the full spectrum of activating and associated resistance mutations in Egfr driven non small cell lung cancer, Florida has spoken to you about 945 and also blue for a five one at the top.

I will focus my remarks on Blu 555.

This slide shows you a table that is <unk>.

Summarizing data that my colleague Keira content presented on behalf of the team last week at the Triple meeting.

What the table shows you is that Blu 555 is fully active against both the LR and exon 19, activating mutations Exxon anything deletion academic stations as well as being fully active on the <unk> resistance mutations shown in the square brackets or the selectivity of the molecule or a wild type and you can see that deal activity is high.

At the bottom row of the table that shows you that the molecule also is fully brain penetration, which was a crucial part of our target product profile, because as we know brain metastases represent a significant need.

In lung cancer.

The bullets on the bottom of the slide highlight for you. The key advantages we see in Blu 555 relative to <unk> 701 first it has a differentiated chemical structure by design in order to alter the metabolic rate and provide us options in that regard and we anticipate that this will lead to an increased exposure of the parent molecule in the clinic.

Secondly, it has improved kind of selectivity and you can see that quantitatively on the second row from the bottom.

You can see the <unk> 10 score is 0.015 literally only hitting a one 5% of the kind of and a concentration of three Mike mauler highly selective molecule.

The totality of these properties came together for us in our non clinical toxicology studies, both the non GOP and the GOP studies, which showed in rodent and non rodent superior selectivity and activity and safety margin relative to Blu 701.

As we think about Blu 555, moving forward as Rod said, we're very excited to enter file our IND in the first quarter of next year.

We're also looking forward to the full scope of the development path in the future. We can imagine the combination of Blu 525% to 94 five shown on the right hand part of this slide.

I'd urge you to think about is that together these molecules will cover not only the common activating mutations, but all associated resistance mutations, while providing activity in the central compartment.

In addition to being combined with 94, five we anticipate that Blu five to five <unk> combined with <unk> as well as select forms of chemotherapy and indeed, even possibly select antibody drug conjugates.

Okay. So now let's move to our CDK to program.

This is a program that has different therapeutic applications from <unk>.

<unk> 55, and instead focus is on a broad range of CDK to dependent tumors and when we think about CDK to dependent tumors, we think in to context.

First serving as a critical node the checkpoint for the transition from <unk> S. Phase, we know that CDK <unk> or cyclin dependent kinase two is misread related in the context of genetic amplification of <unk> one.

This leads to a barents CDK to signaling and rapid progression through the sales cycle.

And in fact, therefore tumor growth and proliferation.

And so when we think about part of the application of our CDK <unk> inhibitors, we think about the precision medicine opportunities shown on the right hand portion of this slide specifically in ovarian cancer, where up to 20% of the patients have see any one amplification and also in endometrial cancer as well as some of the other indications shown below.

A second major application for CDK <unk> inhibitors is in the context of HR positive her two negative breast cancer, where CDK to has been shown to serve as a resistance mechanism to the CDK four six inhibitors. They are used in combination with endocrine therapy right. So we very much look forward.

To start in both of these indications in the clinic as Al mentioned in a moment.

This <unk>.

Broad activity of CDK, too and potential of CDK to what's exciting to us and so we were thrilled earlier this year to have Victoria Brown, representing the entire team presents the profile of Bluetooth to which I've simply reprise for you on this slide.

As you can see the molecules fully potent selective over CDK, one as shown in the fossil laminate fossil or b cell assays.

At selective in the enzymatic context against other CDK family members and then as shown on the final row of the table highly selective against the kind of.

In addition, the molecule has added me and toxicology profiles that are projected to enable clinical combinations would you have just described we believe will be important in the clinical applications for CDK to you.

In the center and right hand portion of the graph or the slide I show you that in fact, the molecule does what we would expect it to do in a CCN IWAN amplified context, specifically in the <unk> three sell model, which is a genetically modified context for cc any one.

We see the expected effect on cell cycle with increasing concentrations of which it's too which was shown through intervention of a single guide RNA to be dependent on retinoblastoma.

And the center panel, we see a dose response of Bluetooth too and the <unk> cell derived xenograft critic.

Critically in this model what the team was able to demonstrate was full activity in the model at concentrations of Bluetooth to that covered the IC 94.

Faso Retinoblastoma.

Without inhibiting foster Atlanta, so just to reprise that strategically what that shows you is while sparing CDK, one and fully covering CDK too we saw full activity right as disclosed in the poster. We also see great combination activity with this molecule.

My colleague Harry fire will represent the team's recent work in preclinical breast cancer models at the upcoming San Antonio breast cancer Symposium I've had the privilege of seeing that data early and I encourage you to tune in to that meeting I think that's going to be an exciting disclosure.

When we think about the Vela trial. This is the opportunity to demonstrate the potential of Blu 222 in the clinic currently Vela is enrolling the phase one dose escalation and we are setting a course multiple dose cohorts looking for safety early signs of clinical activity.

<unk> as well as validation of the patient potential patient selection strategies. The molecule is being studied in both monotherapy and in combination. We expect this to lead to the termination of a recommended phase two dose, which will allow us to begin our phase two expansion studies that are planned as you can see the strategy for these studies follow from the science that we have.

Just discussed specifically, we will be studying the activity of the molecule in patients with ER positive <unk> negative breast cancer as well as patients who have genetically amplified tumors.

Alright, genetic amplification of <unk> in their tumors, specifically in ovarian and endometrial cancer.

In both cases, we will look at combination profiles for the molecule.

I'd like to draw your attention to the bottom of the slide to our translational medicine collaboration that we announced last year with MD. Anderson. This is part of our broad effort to achieve the full clinical development utility of Bluetooth too.

And in this collaboration we are studying new biomarker hypotheses.

<unk> combinations and critically indication expansions that will allow us to identify future important medical utility for Bluetooth to collaboration is going well and we look forward to reporting results from it.

At appropriate scientific conferences and papers and so now let's come back to kit you've heard a lot about kit today.

And it's my pleasure to be able to talk to you about a new kit program as well, but first let me just remind you in the upper left hand corner of this graph.

Our scientific leadership in kit began of course with ever printed but you've heard a lot about today and I won't reprise other than to say that I personally am and thrilled to be part of a company. That's doing such great work with this molecule my colleague Christy Rossi will tell you about our strategy for Blu 263, which is a next generation <unk> inhibitor currently in study.

For systemic mastocytosis.

Recently, we announced a new molecule Blu 654 shown in the upper right hand part of this slide this is a kit exon 13 inhibitor, which the team designed to be used in combination with other kit inhibitors for treatment of kit driven gist and as you heard in our announcement we out licensed this to a company called <unk>.

As a new company a new biotechnology company. This molecule, you'll now see referred to as <unk> 73 in the future. It will be studied we hope in combination in the clinic and we look forward to hearing the results of the studies. So now lets move onto a wild type kit. The fourth program in our portfolio, which gives us the opportunity to still further expand our leadership.

And mass cell mediated diseases.

So as you know wild type kit plays a central role in mass cell survival proliferation, and activation and as you've heard quite eloquently expressed by my colleague Becker Hughes mast cells are primary effector cells in a number of severe allergic inflammatory diseases.

Becca I think describe why they play such a key role in this disease is very articulately and when we think about this is it really is a very broad spectrum and multiple organ systems include severe asthma atopic dermatitis and the focus of this slide which is chronic urticaria. This disease occurs in two forms inducible form and the sponsor.

<unk> form, which you may have previously heard referred to as the idiopathic form.

What is chronic care chronic or the carriers are debilitating inflammatory skin condition, you've probably think about it most clearly from its association with hives.

Called technically wheels right, but these are these bumps that form in your skin that are very itchy because theres a lot of histamine release on them.

Tremendous actual disability caused by this disease because of the sort of chronic nature of this inflammatory condition and your skin. Your skin is an exceptionally important Oregon covers obviously.

Your full surface of your body and as these patients get progressively more and more hives covering more and more of their body. The amount of itching becomes extremely disturbing right leading to sleep distraction sleep disruption stress anxiety and in some cases depression.

In addition, there are further complications that are possible with the disease, including appearance of hives in.

Toward places such as your mouth, the airway or your genitals.

And in addition, anaphylaxis is also part of the disease course, and the severe instances.

The bottom of slide I summarized for you some chronic urticaria statistics to help you understand a bit more about the disease.

Our total estimated point prevalence based on published data is about 2 million patients that is at a moment in time in the U S and four major EU companies and countries and the U K.

The lifetime incidence of disease has been estimated at one 4% globally and when you look into that primary there youll see that the regional distribution of the disease varies quite a bit.

Notably 37% of patients are reported to have not only the wheels are the highs, but also angioedema, which depending on where that's expressed can be life threatening and add in the swelling of the eyes of swelling of the airwaves with swelling of ellipse.

And a full one third of patients report poor control with frontline anti histamines or topical steroids, so clearly a very significant opportunity for blueprint.

To benefit patients by bringing forward, a new medicine, and we believe that a wild type kit inhibitor can be such a medicine. This slide gives you our ideal target product profile in the center across a number of parameters and this is just a selection of parameters. The right hand part of the table summarizes the actual data for a molecule.

Uhm five eight as you can see this molecule brought forward by the blueprint team is fully active in blocking phosphate kit and cells.

Proliferation induced by the kit ligand Fcs.

Exhibit excellence productivity, both over specific kinases, such as PD, if our insulet three as well as broad kind of selectivity as shown to the <unk> 10 score.

And then the last two rows I simply summarize the pharmacokinetic profile of the molecule of course. This is an orally bio available molecule as you would expect from from blueprint, but I'd note also that it has low or moderate potential for drug drug interactions.

And importantly, it is fully peripherally restricted with a K P U of points here for.

The team has identified multiple examples of compounds that meet the target product profile I'm showing you just the one in advanced candidates have safety anatomy profiles consistent with either single agent activity or combination therapy, and we look forward to reporting more about this program.

In the future.

Before moving to protein degradation I'd like to provide one slide to summarize our collaboration with Roche as you know this collaboration was initially announced in 2016 and it is a strategic collaboration with the potential to transform the field of cancer immunotherapy.

In 2019 reported that the collaboration that explored for targets and today I'd like to tell you that the overall collaboration as together explored five targets in total and identified two targets for progression one of those you've heard about before Matt <unk> here. The development candidate has been identified and advanced and we look for.

Core to achieving first in patient in 2023 I'm also excited to say that the second target development, Canada, sorry, a development candidate for a second target still undisclosed.

As anticipated likewise in 2023, and so we've been very pleased with how this collaboration is going forward with erosion, we look forward to its continuation.

Now, let's turn to targeted protein degradation. So you know blueprint for its expertise in the discovery and development of kinase inhibitors right and that's shown on the left hand portion of this slide what we reported in February of this year with the expansion of our discovery platform to include Degraders.

Why did we do this well so there were four benefits that we expected first success with challenging kinases Congresses for which either complete inhibition was difficult to obtain or force. We believe that in fact actual degradation of the kinase actual removal the kinase will provide additional pharmacological benefit.

In some instances, we anticipated to achieve enhanced selectivity for the profile or differentiated pharmacology and then lastly, when applied across the entire portfolio. We view this would give us optionality because again I want to reemphasize, we will continue with our kinase inhibitor program.

Portfolio in fact, we are continuing with our kinase inhibitor portfolio, while we've added integrators we.

We took a bifurcated approach to this with internal investments on the one hand to give us flexibility across programs. We were all remaining ready running and new programs, who might wish to start as well as the announced collaboration with Protium anthem Panther, II, which introduced expertise and also expanded the reach of our efforts by allowing us to start two additional pro.

Grams.

Let's think about this a little bit more.

Scientists likely and say what are we doing here why this blueprint have an edge in this response in this area and what I would say is it begins again with leveraging the blueprint kinase inhibitor library. As you know this is a library of proprietary potent selective and drug like ligands that have been optimized to.

Work at different individual kinase is across the kind of home and for which we are fully annotated. So we know at the outset, there kind of upsell activity.

We can then optimize target degradation by appending a E. Three ligase recruiting element. So these two elements are shown in red for the kinase binding element from Arlington and in Blue Blue Square in the center for the <unk> III <unk> recruiting element. These two items are connected by our linker to form ahead or a bi functional to greater.

Right and that link or it can be optimized by the chemistry team to optimize globally, the physical chemical properties potency and selectivity of the molecule. We're applying this strategy not only to our internal programs, but also to our external collaboration with part of it.

I'll give you a.

Simple example from recent recent work in this program.

This is this is an example, where we're working on a kinase. We can just call. This kinase a or parallel gay in the table I'll direct your attention to the left hand side of the table, where we show the discovery of blueprint the greater one which is active for degrading the kinase with a decent 50 or 60 in animal or <unk> 63 per cent right. This kind of.

The greater was shown to proceed through the expected proteasome pathway and proceeded to shed induces degradation through the expected ligase and this is derived directly using the strategy I showed you on the previous slide that is to say by taking our proprietary replace blueprint inhibitor and converting it into the greater.

What the team was able to demonstrate was that through modification.

The overall the greater molecule they were able to convert this molecule quite surprisingly relative to what we had expected based on the inhibitor S Air.

Two a potent selective molecule that degraded parallel <unk> be a relative a parallel you can see this on the right hand part of the table. We're now then this molecule does not degrade parallel guy at all but rather to do raise parallel b with full activity at 37 animal or D. C 50, and 86% of the Max the team of courses.

Uh huh.

Also quickly explored the possibility of identify molecules that do both and in fact, they were allowed to identify them I show you. One such example, with blueprint to greater too. So this is a simple early initial example, but one that has us quite excited we had long been thinking about starting a program for parallel B and now we can do so opportunistically and in fact are exploring that.

Now I will simply say and summarize from our portfolio impact we've already started five the greater programs three internally to with our collaboration with <unk> and we look forward to advancing areas in the coming months.

As we reflect overall and what the introduction of integrators is done I would say it's done three things for US one is by introducing integrators. We've had this portfolio benefit too we have the ability to have altered profiles for any given target and what I would urge you to consider is to remember that in some cases, a greater will be optimal.

Because an inhibitor will have.

Maximal efficacy in.

In other cases, an inhibitor will be preferred either because we want to fine tune the percentage of time that we're inhibiting the target or because it's recently been reported in some instances the inhibitor bound enzyme actually itself goes on to exert independent biology, integrating it would be untoward.

So it's important that we maintain and drive forward both of these platforms a third benefit that we've seen from introducing this is in the recruitment of new talent with new skills and the introduction of new technologies, which have actually not only enriched showed a greater platform, but also our approach to kinase inhibitors in the future. We can imagine than the integrated platform is having unparalleled productivity.

Being fully scalable and also allowing us to approach new targeted classes and we look forward to disclosing that it can be in the future I'll close with this slide which summarizes for you our preclinical portfolio and contains many of the projects that I've mentioned today Bluetooth Youtube is not on here because thats a clinical stage program, but youll see Blu 525 Wildcat.

Kit and the Io portfolio with Roche as well as.

Targets that are undisclosed and I haven't had the time to speak to you about today.

As shown on the final slide.

When addressing the question that was put forward by Cade in the beginning of the talk are we able to leverage our expertise and infrastructure to drive continued innovation long term growth. We believe we have.

As illustrated here in this discussion and so with that I'm going to turn the floor to my colleague Christy Rossi.

We will speak to you more broadly about our portfolio.

Thank you Christy good morning, everyone, great to see everyone who's in the room and thanks to those on the line for joining as well.

Kate started us off this morning by laying out a compelling vision for our blueprint and 2027.

By which we are going to double the impact that we were able to achieve over roughly the first 10 years since our founding over the next five.

The engine that will deliver that kind of growth is of course, the portfolio and we've already spent time today talking about some of the most important aspects of it the opportunities in <unk> and Egfr.

Discovery platform and our early stage pipeline.

And so now I want to take a few minutes to zoom back out and talk about the sum of the parts and address the question that we often hear from many of you which is what is our overall portfolio strategy and how will it get us to that 2027.

Yeah.

There are four key principles that define our portfolio strategy at blueprint.

The first is to start with the science and I think we heard that pretty loud and clear throughout the day.

This was part of the founding vision of the company Kate talked about the idea around what benefits precision medicine could bring to patients.

This was true when I joined blueprint four years ago and it remains just as true today.

<unk> talked a bit about the aspects that drive our initiation of new research projects and programs.

And they all start with an idea around a target that's important where we can bring as price you put out a blueprint edge Tibet.

The second key driver of our strategy is to diversify risk and again, we see this play out in several ways through our portfolio.

We make routine use of backup program and next generation strategies, particularly against the opportunity areas that we see as being very compelling.

And at a portfolio level, we also look to balance risk and return.

I'd like to think of this as a portfolio that contains a mix of opportunities.

Singles and doubles, where we may have more defined rescue.

And more defined upside.

With triples, and home runs where we're willing to take on additional work for the potential greater return.

And we'll talk about some examples of that in a minute.

The third principle is to build scale.

And again, we see this play out in our portfolio in a few different ways.

Already today, we have seen is that the target level, where we have the incredible expertise and know how around important targets like cat like Egfr that have informed multiple programs in our portfolio.

We also see that in terms of the clinical and commercial infrastructure that we're building in disease areas of interest you at.

And this enables us to gain efficiency and increase our return on investment and.

And we're starting to see that play through in our financial results as well.

As we see moderating opex growth as we begin to see some of those economies of scale there for it.

Yeah.

Last but not least we don't do any of this alone.

We know that we are part of an ecosystem and.