Q3 2019 Earnings Call

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Our children Sir Please go ahead.

Thank you very much good morning, everyone Welcome to New York tool Investor Conference call reviewing operational and financial results from third quarter 2019.

Hi, Mark Sandrine, CFO and head of strategy Hercule.

Good morning issued a press release the reported results for the third fiscal quarter ended September Thirtyth. This release is available on our website at <unk> Dot com.

Leading the call today will be Paolo Pucci, Chief Executive officer of or are you also present from a company or Peter Lawrence President and COO and Dr., Brian Schwartz kind of R&D.

Before we begin please note that we'll be making forward looking statements a decline in the private securities litigation active my to 95.

These statements include among other things projections regarding the timing of key events related to Oculus proprietary pipeline and financial guidance for 2019.

Actual results may differ materially from those projected in the forward looking statements due to numerous risks and uncertainties that exist in our fuels operations development efforts and the business environment, including those factors discussed and reports on forms 10-Q, and 10-K and other documents filed with the Securities and Exchange Commission.

Forward looking statements contained in this call represent the judgment about fuel as of today in our fuel disclaims any intent or obligation to update any forward looking statements except to the extent required by law.

We'll provide an opportunity for Q3 at the end of this call and now I'd like to introduce the CEO of our tool called approach.

Thank you very watch your market. Thank you all for joining US this morning for the Q3 goal.

He would like to you a overview of the structure of the goal. So I will go forth with some introductory remarks, then I will turn into Brian a for a deeper dive into a mendy gold clinical development. The Mark will come back for financial and then we'll open it up working through any.

We're going to try to stay brief although we do you enough time for Q1 night. So used to be was abuse of couldn't be nude and a decisive program. So for US you completing the enrollment or the fees one books through an old our most important them program.

With actual flight three one hour will be pretty you need bidder.

And we focused the recoupment the old the remainder of the piece one on a communication CLL refractories before it was completed as well as rig that's done formation.

In June we presented the first of its kind clean collect PBT data at the how Congress. We showed quite sure response that you for the six Evaluable CLL patients. After the first can 60 to 65 milligram cohort all the pieces one trial 531.

And I had some seed that seems that time I feel fight to one has continued to perform at the very high end of our expectation and we each the that that that we look once you weighed the drug she should continue shortfalls that Andy shows great promise that you'd be anything.

Great promise you that bodes to address the unmet need specifically in the relapse refractory and the people that one new d. This year, our population, but also in other indications beginning with that.

But not only because we have observed at because he accruals for two more died by now.

We once again looking at the year end the excited that to provide additional and meaningfully incremental data update I should.

In December we respect not only a clinical I.P.D. and safety, but for the first time meaningful that deal a meaningful data on durability six months, we'll have faster between the are you have presentation and the ash presentation.

And so those patients that were presented as responses.

Had a meaningful be they'll find to be full world for assessing due to both you'll response.

Looking back at the Port that specifically a these would be the achievement that Oh, we have registered for specifically fight to be one broker first of all we completed the recruitment or the piece, one cardio and direct went and that there I mean, I recommend that piece to dose.

Completely dining lead you enrollment of the piece one portion of the arc to fight to be one clean coal that program enables us to consolidate our position as.

First and best in class.

These new class all reversible BTK you need those.

In our previous Q2 coal, we announced a 65 milligram to de was selected as the recommend that piece do those.

And in fact, we are deploying that goes even at the ongoing fees.

Second we submitted the eating ash abstract in mid July and here, let me give you a little bit of color. Because we have received a lot of questions that so I hope I can answer some of those questions with the next a few words that healthy. So our lead. This data presentation was that you have gone.

In June as you recall.

Several we cast between me when she was when we finalize the full said that was present that to.

To me July when we finalize the abstract submission for ash, so the abstract submission Nova.

Please remember includes whatever the that we cuckoo way.

Up to that Guy.

Not that often they need that that's gone after that we'll be even the poster presentation for us. So therefore, the our submission will include already meaningful and incremental data.

That to what was presented as a baseline yeah, because we had a few weak global observational and we were able to Q2 ways. Some additional days during that period of time.

All of the Ash abstracts are gonna be view on November six nine am okay. So I hope that glorifies a fairly common question, we getting will be in the ash.

Our last.

November six.

A presentation number three.

We have initiated recruitment all multiple piece to expansion cohorts for our two five to one and this is pretty much in line with our pre the previous disclosures. This chemo. These piece through trial is included in our corporate presentation. There has been on our website now for sometime this trial consists the.

It's yellow portion that includes a b <unk> C. One mutant patients as Wallace patients want intolerant to you'd reversible BTK inhibitors, such as Ibrutinib as well as Richters transformation.

That he's also as you can see from the scheme of the trial in our corporate presentation. NHL portion that includes are you with these yell MTL FL waldenstrom and the L.

Style I remind you sort of three important purposes to us, but it allows us for a broader cigna generation effort that will enable us to explore the drug potential beyond its lead indication of yellow.

Secondly, you might provide liking the case of rig the transformation the opportunity to upsize. It did you gave the phase two cohorts into a potential me registrational boards, depending of course agreement with regulatory authorities.

Good either enables the expansion of our clinical site network in advance of Lunching Upland people don't style you see for eight one muted. The CLL also provided that the suitable agreement is reached with the regulatory authorities.

Before I get them that that it's important to recall relative to our work on I feel like the one is the we completed a and this is a bridge to interactions with regulatory we completed the ER. The as we completed the piece one we initiated the.

Cumberland end of phase one.

Interactions with the FDA, so having gathered a sufficient the that relative to safety efficacy and for the regulators duration of response.

We have been able to initiate the dialogue with the FDA, we have disclosed the previous mean several settings that we have a draft design for review with a C 481 mute and.

Leads have line of therapy.

Trial.

And we are looking for more clarity on how valuable that registration strategy might be.

I am pleased to say that the agency responded quickly to all request for any end of phase one meeting and that will conduct this meeting shortly.

Good.

We obviously have to enhance all solid interaction with the.

Get those community that will be by all of our future program.

So we conducted a second this year advisory board to inform not only our immediate lines for the development, but also or expansion of those flat on a longer period of time and I actually I remind you that this is a drug that has a path.

Unlike the goals as a baseline until December of 35, so it's a long patent life, we'd be remiss not to plan carefully for its future, having such a long patent life and having such a big opportunities here.

So our advisors that we met for the second time. This year continued to be enthused by the totality of the factory won the that set obviously everybody is on the CV and therefore, they see life to date that provided that loved it has been Kuwait of course.

And they have encouraged to move forward expeditiously with our current plan. In addition to that they have encouraged us to move into preclinical work that is needed to death and number of combination strategies. They feel will play a very important role industry.

That varies the C b cell malignancies, we have targeted.

And I'm pleased to say that that preclinical work is underway.

Six Im fine now the commercial potential we need to refine.

Our understanding or the commercial potential of this dog eat a different pieces all these.

Long like enabled by this long fab. So this summer we conducted extensive primary for the first time and secondary but for the second time research, we were able to conduct primary research because idle yeah.

The target product profile fairly clear target product profile has emerged at least for these drugs as a single agent.

We have yet to establish the target product profile.

For the drug in combination, but we havent notional one.

Not surprisingly given the favorable profiles the has emerged for five to five to one that yeah. We had the possibility to go much more in that we'd be second exercise.

All bought lifecycle management for the drug.

And if anything the second exercise multiple screens and much more expensive than the farm the first one.

Coupon the DC, indeed, a blockbuster opportunity.

Even if we take CLL alone.

And that opportunity in CLL eases, driven by the U.S. market.

These opportunity and we'll learn these incremental it can be further enhance following a confirmatory trial.

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And we have several design under consideration that would expand very significantly Denise patient population targeted. In addition, we can then further expand that patient population beyond CLL into some other select the b cell malignancies, as a single agent and most often in combination and.

Thats one of the reason why we have such an expensive. These two multi arm trial and we are initiating already the can be notional work.

On several fronts.

Finally, we will have the opportunity to further expand the market by going ex us and actually I remind you the ex us markets. Even the developing countries are going to become attractive mean next decade, the moment, the patent or be bruising of expire and the usage you that we grew to be goals.

Up due to the removal of the price barrier.

Hi.

More inexpensive brutally get bore utilizing front line more patients will be available for second line spring Onest muted.

Very very simple math.

So switching gears to overgrowth. This concludes the section about five to be one it's a long one but you can imagine that the lions share of our energy goals. The into these program right now, it's very important to us to maintain and enhance our position first and.

I think loss among these new class of reversible BTK inhibitors that hole in our view a lot of promise switching gear door now to all overgrowth diseases here, we don't we put the rest of out of effort.

We've been focusing on initiating the registrational trial in produce Enpros. We have opened sites worldwide and we were very pleased recently to one now the first patient being dosed in the style these tremendous excitement.

For a.

Among patients the patient community for this they first opportunity that they have to enroll their loved ones in one such style and Brian could touch it.

In person.

Past weekend, where he was with.

The patients the association that their annual meeting we that in fact huh.

I thought there might to Brian that will give you a little be more detailed on the clinical activity. Brian . Please thank you Paolo.

Let me start with air Q five C.

Potent reversible dual inhibitor of both wild type and see for eight one its mutant BTK.

Preliminary results from our most recent presentation that.

Suggest that 531 continues to have a manageable safety profile and demonstrates clinical activity in multiple b cell malignancies.

Pharmacokinetic data shows that subjects, receiving 65 milligrams exhibited steady state Siemens concentrations.

But one micro Motorola and the plasma half life is in excess of a day further demonstrating that sustain and complete BTK inhibition can be achieved at 65 milligram once a day.

Maintaining a semen concentration above one micro mode is predicted to be a critical factor in achieving anti tumor response and a recommended phase two dose of 65 milligram appears to comfortably exceed this threshold.

As we approach another meaningful data disclosure at ash it might be helpful to recap what we have reported thus for in terms of clinical activity observed.

As you will remember we did create a total of seven partial responses in full separate tumor types.

For CLL Sheeple eight one s. mutant patients from cohort seven initially at 65 milligrams.

One richters transformation also from cohort seven.

One follicular lymphoma patients initiated in the first cohort and subsequently dose escalated who remain to respond to offer.

Two years on therapy.

And finally, a deal bcl patient from cohort eight dose that 75 milligrams. This patient was not yet at PR at the data Tuttle for E. R class was late to reported as a PR in the context of our financing in late June .

With respect to duration of response in CLL only two of the for CLL P. AWS.

Just described had received the second scan, which could approximately five months on therapy.

Both these patients remained a PR at that time their responses were confirmed and they remain on study.

At this year's Ash, we will present substantially more durability data for these and other patients, including second scan at approximately five months as well as many third scans performed at nine months for these patients.

In terms of safety.

Q 531 continues to have a manageable safety profile and the side effect profile with respect to timing frequency and grade of adverse events remains on poff with what was presented at EEI Hall.

To date, we only observed the one deal key Netlist described last March and did not reach an MTD as described in the trial.

As we conclude the phase one portion of the trial, let me transition to discuss the expansion trial, which is already dosing patients.

Seven sites are currently active and we plan to activate approximately 30 more sites in the U.S. and the rest of the world.

As Paolo mentioned the trial is divided into two parts, which will include eight specific an expandable cohorts.

Later, we plan to Ed cohorts to test high priority combinations that we will select and disclose.

Our primary focus remains on CLL.

At a minimum who have failed any reversible BTK inhibitor.

We all share deal to speak very shortly with the FDA to explore as fast to market registration trial.

In parallel we are conducting preclinical combination studies and working to develop and easier to administer companion diagnostic to rapidly identify and diagnosed patients with the C. Four eight when asked mutation, we'll see or other Stifel eight one mutations.

Moving onto Richters transformation.

Which as you know is a devastating diagnosis for affected patients and carries a very grim prognosis.

We have treated a handful of patients in the phase one portion of the trial and fortunate to have observed preliminary signs of clinical activity.

As soon as we have a more robust dataset, we plan to discuss a registration trial in this population with regulators as well.

And we continue to enroll rictus patients in the ongoing phase two expansion trial.

In time, we hope to have the option to expand that cohort into a registration cohort in an area of extremely high unmet need.

Let me now move over tumor inserted in re overgrowth spectrum disorders.

As previously announced we have dose the first patient in our Registrational mosaic trial.

Hope is underway for these patients.

As you know there certainly is a potent and selective 8-K T inhibitor.

Our objective is to be first and best AK teen EBITDA in Proteus and pros family of rate overgrowth diseases.

This family of diseases is ultra rare.

Very heterogeneous and the patients currently suffer from a dismal quality of life and early mortality.

No systemic therapy has been approved for these patients and the only current treatment is surgery.

I'll now registration program the mosaic trial.

This will consist of one protocol divided into three or four cohorts.

The first cohort will focus on Proteus syndrome, and will enroll at least 10 patients.

The second cohorts will focus on pros family of overgrowth disorders, and will enroll at least 20 patients.

And the third and fourth cohort will be signal generation.

And compassionate use on sets will include patients from either group, who do not qualify for cohorts, while all too, but otherwise benefit from treatment.

For Q five everyone, sorry, 751, the next generation 8-K T inhibitor.

We recently published two posters at the Triple meeting.

Highlighting both preclinical and clinical data that supports seven five widened highly potent and selective 8-K T inhibition profile.

In addition, we plan to announce the final data set from the ongoing phase one trial once the trial is complete and data has been.

Finalized.

Lastly.

For their resents another.

Our FGF all inhibitor.

Our partners, that's the Leah and sentiment continue to implement their plans for the Registrational phase two trial and I see CA and towards the phase one initiation in China, respectively.

Specifically.

Best delay I have announced expansion plans for the clinical program, both a single agent and in combination with a PD one inhibitor.

With that I would like to now turn it over to more to go through the financials.

Thank you Brian .

The company reported a net loss of $10.7 million or nine cents per share for the quarter ended September Thirtyth 2019.

Compared with a net loss of $5.6 million or five cents per share for the quarter ended September Thirtyth 2018.

As of September Thirtyth of this year, the company had approximately $174 million in cash and cash equivalents.

Revenues in Q3, 29 team or zero point $2 million compared with revenues of $5 million in Q3 2018.

R&D revenue this quarter was primarily.

Comprised of Reimbursable manufacturing costs.

Licensing agreement.

R&D expense for Q3, 2019 was $8.3 million compared with $7.3 million for Q3 2018.

<unk> expense was $3.2 million in Q3, 2019, compared with $3.4 million in Q3 2018.

For 2019, Arqule expects revenue to range between two and $5 million net losses expected to range between 40, and $43 million and that loss per share to range between 35, and 37 cents per share for the year.

Our fuel now expects to end 2019, with approximately $160 million in cash and cash equivalents, which is projected to fund the company's operations well into 2022.

With that I'd like to turn the call over for Q and eight operator, please feel free to open the line for questions.

Sure.

At this time I would like to remind everyone in order to ask the question. Please press star and the number one on your telephone keypad.

Plus for just a moment to compound degrading a roster.

[noise].

Your first question comes from the line of Jonathan Chang.

Your line is open.

Good morning, and thanks for taking my questions. You were on first question just to clarify I have you had your end of phase one meeting with the FDA, yet and any color on when we might expect to hear more about Registrational trial design.

No we have not had the opportunity to interact.

Normally with the FDA, yet and as we say than at this call. We would expect that to happen in the very near future.

And depending on the quality of the interaction I mean the duties.

Actionable plans the car model. It then we will disclose accordingly.

Just keeping the mindful of the competitive environment, but.

But once we have something that we can discuss will we don't have you got this time.

But you know what the plant so we going into those discussions to has at the end of phase one meeting we have a well developed concept for a.

Biomarker support.

Plan.

That we can see that fast to market for conditional registration you see for one.

Patient, we have be working hard actually Peter has been leading the effort in developing a biomarker strategy, which is necessary.

Companion for that kind of request should there be time left an opportunity we would like to understand what would the FDA.

Consider to be an approval body does that four week the transformation.

So that we can calibrate our.

Yes.

Read this portion of the phase two study eventually accordingly, it's a lot to walk I don't know how much we going to be able to cover.

The first discussion with them, but there was our best.

Got it thank you.

Second question.

And I wasn't sure whether to go there, but since you mentioned the competitive landscape and as we approach yearend. How are you guys thinking about the competitive landscape for Fivethree. When I was several readouts expected reversible BTK inhibitor space College.

Well one the other reversible that need returns.

Through our proved that they showed the equivalent to what we have shown about Nina I'd be happy packing hand.

To talk about our deep.

In comparison, so right now.

Our compared to do use the combination we viewed to be Veneto blocks.

And we started to work to will compete with them.

Preclinically.

This is our competitive the either when they come we'll see.

We'll see what they have at the ash.

We have a big target with this drug.

I continue to maintain that with such a long patent life for distraught the horizon is much beyond the ultimate horizons as much beyond what the everybody's thinking right now the point of entry means.

The one that we've been discussing we she's refractory patients we see 0.1 mutated.

But.

There is one or two or eyes and beyond that point of entry.

And.

The other reversible the needs that are not there right now so after that.

We'll see what the these assets before everybody relative to point of entry, which is one that we treated patients which are refractory and then I can maybe speak more intelligently right now I can't.

All we can say same old say mold.

The glass comprises four compounds towards those compound to bring forward the claim of being highly selective again PDK we.

Our kind of in the middle of the path with.

Claim or being.

Domain selective for it.

Selective members of three just three gaming customers involved in B cell malignancies, and then on the other elements and the effect. So these are very interesting compound, which she is a dual inhibitor assets should be roughly three years VPG and that's as much as anybody can say because that's not a lot more began to discuss.

Got it and just one last question for me.

Can you expand on the preclinical find to line combination studies being conducted.

Well, that's the it depends on local award.

For the combination study you in our can I extend Oh, yes, we are doing that we're going to go work at this point in time and Yara.

Defining how will we proceed in the clinic once we've passed up or clinical work.

We're not in the position right now to say more we have a very significant.

We were experiment that some of our collaborators have insisted on.

But that's going to take some time, so that probably for next year.

Got it thanks for taking the questions you work on.

Your next question comes from the line of parent Kumar.

Your line is open.

Hey, good morning, everyone and thanks for taking the questions.

On our right. So first off for the Ash I should we expect any meaningful update our safety and Mechanistically Ddtank diversity will be together class kind of Hawaiian.

So on the typical easy simple related toxicities like leaving our atrial fibrillation.

Well.

Every every update.

Has always included the safety we are updating after all of room on the phase one trial in the core objectives at least one trial these to establish safety.

Hello ability and dose so of course, yes, there will be a safety update very much following the formal what we presented that.

I will remind you. This is our first update from these phase one trial. So I think is one of the most of the the phase one trial that I've seen we presented at Ace yard that we present is that you had that we presented at ash that we presented against that anyhow and now we concluded by presenting at Ash.

So you all have had the opportunity to follow.

The evolution of these drugs you know in real time across the phase one data you have a presentation that as you might imagine being the first that we do the reviews of the forces master found that the the interesting in incremental as we presented to them.

Then so they will be a safety.

As far as.

As a.

Your request you'd be beyond fear and ignorant of me not to to say that decline of side effects. You mentioned the cardiovascular side effect for any class of drugs can be meaningfully observed in the in the very large.

Studies.

And.

He believed to be but that reports some of those side effect has been observed as being those even in large population by now they have very large database. Thus far we have not absorb them and I can speak for our own drug I cannot speak for the glass.

The other dogs in the class will speak for themselves, but thus far we have not observed them. So it's worthwhile for me to say that we have not.

We have not seen a second deal Dean the style as of yet and we have not reach MTD in this trial as of yet.

Brian you like to and then our cardio safety I think the to the two things that you will get at Ash will be long term safety because we now have.

A bunch of patients on drug.

For a period of time in terms of the first month or two is not a huge number of patients added there, but you will get a much longer duration of therapy and see how patients tolerate.

The drag in net perspective.

In terms of the cardiovascular and bleeding, we continue to look both pre clinically as well as carefully clinically for any evidence and so far have not seen any signal of those two.

Vince but is the phase one study so the numbers as I say as people look to properly assess the existence or otherwise.

And we'll signaling in in that framework that you described.

Thank you and maybe just one last one on FDM meeting.

What are some of the disclose how do you plan to have let's say that gave meeting is positive.

In terms off maybe patient number our endpoint for pivotal study and.

Related to that do you plan to discuss confirmatory study as development FDM. When you have this in a few weeks or so.

Well as ours I think the last part of your question I was mentioning before we are not even sure we're going to get to the point of being able to discuss.

What would.

A.

Registrational cohort for reap the transformation of my bit and the definitely I would think you'd be premature for us to bring up the topic global confirmatory trial.

If the agency where to bring it up but then we will listen.

And that's going to be the extent, but for now.

And our size disclosures as I have mentioned before.

Well the moment, we have something that we believe it is a solid and and can be disclosed and.

Peter reminds me has to be disclosed then we will consider that.

For disclosures as Oh.

The first opportunity and certainly might be around the ash.

And then after actually will be I guess Q4 coal or before but.

That's a fluid or not having even had the first contact with the agency.

I can't do better than that.

We do believe that the agency should be receptive to what we are there to delta because this is an emerging unmet need.

The first time, the we're introducing a biomarker.

Which is emerging.

In the significant way and so we're hopeful but we have to have the discussion to see if our hope is justified.

Thank you Paula Brian in March and congrats on the progress. Thank you.

Your next question comes from the line as Tony Butler.

Ladies okay.

Thanks, very much three brief questions, if I may and I'll just for cyber them all so.

So that so that.

It will be shorter.

One is despite Brian for hurt you correctly.

Currently have seven sites open controls actually with five.

And then you will open if I heard correctly 13, that's one three additional sites in the Western Europe and.

And I guess.

That's correct how long do you think it will take you to actually open those additional sites and by time I'm actually.

Thinking about its not just.

Oh, sorry approval, but it's also.

A rough time for them to be able to.

Bring in their first patient that's number one.

For two is if I'm correct you have to.

Types of pills 120 milligrams, a one five and so you take for effectively to get to the 65 on a QD basis. The question is are you happy with that can you actually manufacturer.

You know a 65.

Milligrams single tablet would you want to do that or does it matter and then thirdly and the discussion with the FDA.

Whatever you end up discussion just leave Richters out for the moment.

Would it actually lead to a change do you think and what you're doing what the cohorts currently in this expanded phase two thanks very much.

Okay. So.

Brian is going to take the first question, which is around the number of sites that are open pit the overseas CMC isn't it just second questions relative to fuel.

Milligram and then I'll take the last one.

So just with regards to side three divided up the sites into a number of different buckets in a way to CLL. We believe we have sufficient sites and we need to update clinical trial Dot Gov.

To get most of the CLL patients enrolled in a reasonably good timeframe a lot of the other sites will focus on some of the rare at tumor types or rare lymphomas.

That fall into the other buckets. Our plan is to have everybody up and running bye.

The first quarter next year.

So that the trial will be able to fully enrolled by the end of next year. Some of the tumor types already era and will may take a little bit longer.

Okay. Thanks, Brent Tony Squeeze Lawrence how are you regarding dosage strength CMC, we don't talk a lot about it because a lot of things we're doing we consider proprietary but what I would say is we are.

Hello, I mentioned earlier in the presentation that we are doing commercial studies as we as we move ahead with our or core product form.

We're thinking about what the what the best form would be for patient.

Obviously, we want a we want compliance to be highs. So you can imagine that we would be thinking about.

One or two dosage forms that might simplify things, but we're thinking about a number of things and we will we we will come up with what we think is an optimum product by the time, we reach commercial launch.

Entities.

Some IP that we are developing around.

Thats PMC that's why.

We we didn't meet our disclosures because.

Until that happens I believe the we're better so keeping for our self and how would the last question, though the three was how would our meeting with the FDA change of our plans.

One one thing that the FDA meeting could change relates to one of the three cohorts for CLL. So we have three cohorts over in the one is a separate one new data one is for a.

For tolerant patients and one for Richters transformation in these section of the trial, we will see changes based on the discussion with the FDA. So the one that is how likely to change it is the one that ease.

Intolerant to boot to me, it's very interesting information for us to collect we don't know how interested d. These for the after FDA.

But but that's my in my opening right now, let's be slightly to change the first cohort the one that is.

C at one a new d. the laser line of therapy.

They have seen earlier lines of therapy universally need to my actually change might close altogether. If we are able to find an agreement with the agency for Registrational trial that also carries a biomarker playing with it the phase two does not carry a biomarker plywood.

He was not part of the discussions with the agency at the time.

Then that will close down because obviously, we don't want to compete with ourselves we want all all sites to turn their attention to recruit Registrational studies that are in that setting. So that's one change that you could one could getting much in the recent transformation court right now is a spec.

As a second generation cohorts.

Sure we have the opportunity we have a clear understanding or what the agency, we'll be looking for in terms of number of patients enroll endpoints relative we assumed response rate as well as duration of therapy. She is generally should then that is the next one that could change because that could be.

We expect to become a a registrational cohort as well.

NHL is very hard to two hypothesized right now.

And now the change that could happen to the phase two is that we might try to bolt on to it.

Combination cohorts.

But that is for next year.

I hope that answers Tony.

Oh It does thank you so very much Peter appreciated Brian Thanks for your welcome.

That's right.

Okay.

Your next question comes from the line of Gregory ran Sir.

Your line is open.

Hi, guys. Thanks for taking my question, you're walking or.

Hello.

You speak about I'm doing some odd commercial.

Opportunity working landscape work early on I'm, just curious on that you could comment a bit on the strategic cards you hold with five free one just around the several upcoming points of interest and value creation potential in any cross or that you could be at what is your latest thinking on this really to realization that is going.

Moving fast direct to market with them narrow populations versus balancing the prospect of going broader I'm well with this prompt you to think about.

Accessing greater resources, bringing out a partner even to help them, perhaps tackle those larger opportunities that you're alluding to and similarly would any emerging are evolving competition.

Maybe at or at a distance of your heels alter that thinking as well. Thanks.

Well. Thank you Greg So let me take though the appeal of your question or with any emerging competition change our thinking.

Indeed that there there has been very big change because for the first time, we have one or the big pharma companies that has entered the space with the acquisition of a lot. So by Eli Lilly now Eli Lilly has.

The reversible inhibitor a claim to be highly selective reversible and need to go so somewhere there were different profile from our but the needs of a very big company. They can deploy resources, we never mind, the even though you even if we get the tremendous support from our current shareholders and I'm sure we'll get.

Support from our future shareholders, there's no way in the World. We can match and we'll limit can bring to bear here. So we are mindful of that.

I had to say that.

So far the entrance of mainly in the field has produced supposed to be positive results for us in that while before when I would go talk to invest the about reversible than it is people would say, yes, you know the story.

Now they say.

No we want to learn what the region could be for reversible inhibitors. So the enters of Lilly has brought a lot of interest.

In a in our story as well justifiably, so and I have seen the full results of our second lifecycle plan, which was very rigorous and conducted by an independent consultancy, which probably doubled word in this matters and so I I I imagine Lily.

Looking at the same.

Commercial projection that I'm looking at and I would think they will compete vigorously.

So that's one thing.

So on that basis, obviously, we remain open to to gaining more support.

For our program provided that the framework is right.

No discussion will start at all what is going to be Europe from no that there will be the very last thing we discussed section the financials, we need transaction will be the very lasting the first thing to discuss is going to be how would you how.

To create more value for our shareholders.

Shareholders by helping us to go much broader and much faster that we would be able to do on our own.

And then and then and then if the result in meeting on the mines on that item then everything else can be discussed, but they said.

We can't wait so we going forward full force with all the resources, we are able to master you've seen that we have.

Focus our call on our 2531, mostly and you've seen that we have very little updates for.

So I wont buy one we had some of these four.

He ran city be rare disease, but that is a small part of our effort into the is a big part of our value proposition a small part of our foot. So you can see that we are the ordering the near totality of our effort to two five to one right now.

And that means that the other programs like several inphi. One then all getting as much attention to so they're not proceeding us speedily as we would have expected 12 months ago.

So we are open to discuss with anybody provided there is no conflict or.

Competitive.

Competitive issues.

At the same done we're not waiting for anybody with will fall within our own.

A number of shareholders have supported us in our last raise.

We all know and and they supported that for us to run.

As fast as we can on our own. We also don't forget that these patients have very poor prognosis and they need therapy sooner rather than later, both the FIFA, one mutated patient and even more so the read the transformation patients. So that's the that's.

Where our mine is that the today, but we're open minded people, we have partner drugs before we might find the drugs again.

And on the basis of the strategy that underpins it.

As to if partnership concept the rest you do.

Great. That's helpful. Apollo maybe just one more for me, perhaps for you or or or Brian I'm. Your mentioned earlier, just about you know competition really being imperfect plus.

Banana KLAX I'm just curious if you could provide some color on your thinking around mutation profile of patients.

First time, imbruvica only or or.

Reversible only therapy versus really the future with respect to that Inc.

Plus banana KLAX, how how should we perhaps thinking about.

Mutation profile potentially changing.

In the future. Thank you.

Maybe I can take the city and help US your question right.

With regards to the combination and the development of the mutation I think it's still relatively early days.

In terms of which resistance mutations.

Must develop however.

There are couple of things that already merging with the combination one is the fact that the combination may have a limited duration of treatment followed by a potential maintenance period with the Britain that they mutation would develop but it's really.

Very early on in terms of that what I will say is that both in others in other literature and in some of our patients if a patient receives.

A co violent BTK inhibitor, followed by a bcl two inhibitor that mutation can persist once the patient progressions. The bcl two inhibitor. So one would imagine that you could develop the mutation.

Even on value on them, while you on both drugs as well, but it's really too early to say.

Thanks, Brian appreciate that.

Your next question comes from the line of Chad Messer.

Your land.

Great. Thanks, Good morning, and thanks for taking my questions. So okay. Good morning true, yes, good morning.

Obviously very excited for the ash, both abstracts and presentations. So all all my come all my questions for on those.

On that compound until we have that data.

Got it so maybe just a couple of quick ones on 751 since you just put out some to date on that recently I know, it's a little bit earlier it looks like.

75 milligrams is what you're going forward in the expansion cohort. If you selected that dose and are you gonna have to dose escalate for the for the combination arm.

So Chad.

75 is a single agent dose, we have a lot of experience, there and and finishing off the rare mutations in that isn't that cohort in terms of the combination with the nast resolve and with tax effect. So we started a little bit lower and then dose SK.

Later to 75, but there's a high probability that he will end up with 75.

As the as the recommended dose.

Chemotherapy is always is it's always difficult.

But.

With the investors all we don't think there's going to be any any issue.

Okay. I mean, maybe just a question on this pick three C.A.H. 10, 47, our mutation it seems.

Others have also observed as as you did that dismay correlate with response, some any any plans to pursue that.

It is one of the driver mutations and that is one of the it's actually really nice because that's the mutation we see the pros as well which seem to respond.

Better too to mirror answer to.

But it may be that not all PR three came mutations are equal and we will have to focus on a number of the driver mutations the can fit 47 or is one of the most level the more common mutations or low or what are the more common mutations.

But that is really where we have seen more of activity.

With that specific driver mutations.

Okay, and then I guess, we're still waiting for a full presentation of the phase one data.

You do have all the patients from the dose escalation in their response and duration of therapy already kind and here just wondering.

You know one additional day, it'll get highlight them on and I I presume more safety data since we don't have a ton of that in here, but what else maybe in the thing I think we just discussing exactly that with investigator, where we got up to what the plans or for that for the data for the phase one dose escalation data and the.

Phase one expansion data.

And we'll let you know as soon as we've agreed upon with MD Anderson will we we'd love to presented.

Alright, great. Thanks, guys.

[noise] you walk.

Your next question comes from the line of add White.

All night vision.

Hi, good morning, Thanks for taking my questions.

So maybe.

Maybe if I could switch gears just.

Quickly over just the mosaic study.

Congratulations on enrolling your first patient.

Is this patient a.

Bruce patient or Proteus.

Syndrome patients.

[noise], so we have enrolled.

A number of patients as often as of now and we can say that both both groups have been enrolled as of now quote one and we don't really talk too much about the accrual.

But but they both but both of being enrolled as as you have now.

Okay, and essentially not going to talk about accrual I was just wondering if maybe you can talk about the.

Number of sites open in are you, having any issues identifying.

Patients to enroll Im just trying to get an idea of how quickly we're going to be able to see that the trial enrolled.

[noise]. So this is just a little bit difficult to predict.

In terms of how the Krueger I just returned from the Proteus syndrome Foundation meeting, we we've clearly identified.

I would say more than the number of patients we would need in the trial. However, they have to go through assessments at the appropriate.

Physician North Dakota, one of the more difficult components that we stumbled across enray diseases is that it takes a while before patients actually get everything together to come into the trial. These kids that have to travel.

Couple of hours on a plane to get to one of the sites and the families have to put a lot in place before all the visits a shade yielded all that all the test of share deal. So we finding that it's been very difficult to predict it's easy to identify the patients, but it's difficult to predict when they're going to be enroll.

In terms of sites, we have a number of sites open in the U.S., we have at least two enrolling anticipated number more enrolling we have three sites as of this week opened in Europe . So we feel that things have started to really pick up in the last month or two and.

And the Soc in Australia, which has just opened this week as well so we feel that the trial will definitely pickup in the next few months.

We will report an updated our next call.

So the challenge.

Your question seems to imply that we might have a challenging identifying the patient.

That's not exactly the case I would say I would say that the I would say that the objective. The challenge we have is the logistics.

All things.

But we have had experiencing advantage that challenge in the basta, particularly when we had the the NIH dial open where there was one site on the open than people had to travel significant distant have a long stay there.

And is that we were prepared but they still that's the major challenger in the trial, but equally for produce.

Okay, great. Thank you for the update you on.

[noise] once again, ladies and gentlemen, if he wants to ask the question. Please press Star then the number one I know telephone keypad.

Your next question comes from the line of Justin Kim.

You know mindset.

Thanks, everyone. Thanks, Thanks for taking the questions from my caution.

I'm, just maybe with respect to the phase two expansion ongoing for five free one well the team communicate if and when a cohort has been expanded by 14 patients and.

For the requisite three partial responses do those required to scan.

The departure sponsors who wants to scan so needs to be confirmed and the updates will come as they have come in device for the phase one.

More like.

Preferably in a in the setting of major conferences.

Okay, Great got it kind of and then.

Among the BT KC 40, onest patients treated I believe the enrollment criteria cost for at least two systemic therapy. So.

Do you have a sense on whether the majority of these patients will be then o'clock experience based on the current enrollment experience.

So it's really mixed URAC with the FDA and the initial one was at least two prior therapies.

It's really mixed at this point in time, I'd say about wanting to me as had been at a class.

All of them heavily pretreated, although most of them high risk.

Falling in one of the high risk categories, but I'd say that right now one in three I think as we move to.

More sites it may change a little bit.

Okay. Thanks, Brian .

And maybe just on the preclinical work being done for for combinations do you have a sense on when you might be able to sort of publish those those findings of five to one in combination when things such as.

10 o'clock.

Our goal is to try and get as much information out of these preclinical study so they will run longer than most other studies. So sometime next year I would imagine we'd like second part so Nicola yeah, we would really like to see.

A number of end points here looking at.

Some of the questions Andrew asked earlier about the combination and onto them in the preclinical as well.

Great and maybe maybe just a final question as we think about the update at Ash can you just remind that sort of what the schedule for scans is after the second one.

Yes, so it's the first one around two months the second one between.

Between four and five months then at that three to four months off the that and then they stop going onto a six month initiate deal.

Okay, great. Thanks, so much everyone.

Sure.

I'm showing no further questions. This time I wouldn't I like to turn the conference back to Mike said you're right.

Thanks, everyone for joining this concludes the call.

Ladies and gentlemen. This concludes today's conference. Thank you for your participation have a wonderful day email disconnect.