Q3 2019 Earnings Call

Ladies and gentlemen, thank you for standing by and welcome to the alternative Therapeutics third quarter 2019, Investor update conference call.

At this time, all participants on the listen only mode.

So to speak of presentation, there will be a question and answer session.

The ask a question during the session you would need to press star one when your telephone.

Please be advised that todays conference is being recorded.

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When I like the hand, the conference over to your Speaker today, Renee Leck direct of Investor Relations. Thank you. Please go ahead Madame.

Thanks, operator, good afternoon, everyone and welcome to orchards third quarter 2019, Investor update you can access slides for today's call I'll be going to the Investor section of our website Orchard T X dotcom.

Before we get started I'd like to remind everyone that statements. We make on this call will include forward looking statements.

Actual events and results could differ materially from those expressed or implied by any forward looking statements as a result, various risk factors and uncertainties, including those set forth in the most recent form 20-F filed with the FCC and any other filings that we may make.

In addition, any forward looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update or revise any forward looking statements.

With that I'll turn the call over to our President and CEO Mark Rothera.

Thanks Renee.

Good afternoon, and welcome I hope, you're all enjoying the annual excitement with the release of the Ash Abstracts. This morning, which included several from watches gene therapy portfolio.

The purpose for today's call is twofold.

Firstly, we'd like to bring you up to date on our progress executing against our corporate priorities, while reviewing some recent business highlights and secondly will set the stage for the data releases from a registrational programs in 80 ice Kid and Wisco doldrums syndrome that had been accepted at ash.

In December .

I see us so Bobby Gaspar will cover the second topic in more detail after my opening remarks.

Then Frank Thomas Orchard, CFO , let's spend some time reviewing the third quarter financial results and outlook.

I'll return to close with a discussion about commercial strategy as we prepare for multiple filings potential approvals and product launches in 2020 and beyond.

Before I highlight the datasets coming up at Ash I'd like to take a step back to remind those of you who I knew it to the story, who we are and to recap the tremendous progress we've made this year.

Orchard is a pure play gene therapy company with a focused approach and singular mission to deliver transformative and potentially curative therapies to patients often children suffering from life threatening red genetic diseases around the world.

Our expertise lies in developing ex vivo autologous hematopoietic stem cell H S C gene therapies.

A platform approach that has demonstrated clinical proof of concept in five different diseases in our portfolio so far.

As a company we view the time patient as a temporary label and see the opportunity for lifelong benefits, including the potential for therapies to be curative.

With over 150 patients treated across our portfolio.

A follow up showing durability of response going out to eight years old, though we believe we have one of the most robust and comprehensive clinical data sets in the field of gene therapy.

Now turning to the progress we've made.

29 team has been a stand out yet for orchard.

Let's first focus on our lead three programs in Metro chromatic lipodystrophy, the LTL 200 program.

It is good the LTL one on one program and was the LTL, one or three program.

For all three lead programs. We have published presented had an abstract accepted for the complete Registrational datasets.

These include clinical measures of efficacy and safety data generated with a fresh gene corrected stem cell formulation.

For ml DNA Da's. Good Weve also presented results from two cryopreservation studies that were conducted to evaluate the performance of cryo versus the fresh cells.

As part of the bridging work for upcoming regulatory filings.

We believe a cryopreserved formulation will provide a much more convenient and beneficial experience for patients around the globe by enabling them to be treated near the homes.

Well that sells travel to and from a manufacturing facilities.

We are well in a way towards delivering on our mission for patients with two upcoming regulatory filings 88, skid an M.L.D.

Accordingly, Orchard has grown its commercial capabilities in the U.S. and Europe .

As we build an organization dedicated to delivering HSC gene therapies to patients worldwide.

I'll say more about this later.

The neural metabolic disorders franchise in particular has had a wealth of news flow this year.

Creating additional momentum for these programs.

This is a therapeutic area, where we are especially excited by the potential application of our HSC approach.

Most patients with these conditions do not have effective treatment options.

As is the case for our most advanced neuro metabolic program M.L.D.

Not only has no till 200 made tremendous progress, but a promising pipeline of earliest stage assets. In this franchise is also advancing.

In May we licensed in an exciting new program from our partners as a teenager in Milan for MPS, one I have seen encouraging preliminary data in the ongoing clinical proof of concept study presented a S. S. I am in September .

Furthermore, this morning, we announced the acceptance of the clinical trial application for our first study in MTS, three a or sanfilippo syndrome Taipei.

And we expect to begin enrolling patients by yearend.

This will be the seventh clinical stage HSC gene therapy program in the auction pipeline.

The M.P. Uthreeoeight studies being conducted by the role Manchester Children's Hospital.

Which treats it a patient under specials license outside of a clinical trial earlier this year.

The patient continues to do well with favorable enzyme and biomarker data at six months, indicating the treatment is taking effect.

Now turning to our Ash news.

The date or in this morning's abstracts, Mark the achievement of two important clinical and corporate milestones for the 88 kids and was programs.

For radio is good we are presenting for the first time the data from 10 patients treated using the Cryopreserved gene modified stem cell formulation of LTL, one or one.

As Bobby will review, we now have to support datasets, one in 80 Ace good and one in M.L.D. that was presented at E.S.P.C.T. a few weeks ago that demonstrate that cryopreserved formulations are engrafting in the bone marrow and performing like the fresh sell formulation.

For wash the day during this morning's abstract confirm that the eight patient Registrational trial has met its primary and secondary end points at the three year follow up time point as per the protocol.

The median life expectancy today have a was patient is approximately 15 years with supportive treatment.

And there are around 3000 to 5000 patients living with a disease in countries around the world that typically reimbursable from drugs.

So the pool of prevalent patients lives. This condition is quite substantial.

We expect to submit regulatory filings in the U.S. in Europe for this indication in 2021.

With the results from this morning's abstracts Orchard has achieved each of the clinical data milestones, we laid out for 29 team.

I'd like to congratulate the tremendous cross functional effort within auctions.

And among our collaborators, including SRT jet the of the Dalai send Raffaele you Seattle, you CLA Boston Children's Hospital, the University of Manchester and others that have made these achievements possible.

Let me now handed over to Bobby to dig into the Ash abstracts in more detail Bobby.

Thanks Mark.

He wants to review all of the compelling clinical data highlighted in this morning's abstracts.

With free clinical presentations featuring dates on dozens of patients they send us well showcased the breadth depth and your ability of orchards diverse pipeline and methodic stem cell gene therapy.

The data and 88, good end was all the culmination of longstanding pioneering work in gene therapy for these life threatening diseases, where I believe we have the potential to establish a new standard of care.

I'll start by reviewing DHL, one or three abstract for patients with boss in greater detail.

We should older syndrome is a life threatening hymns logical condition, the presents with severe platelets and immune system abnormalities.

Two major clinical aspects of the disease, and consequently, the highest causal mortality or severe bleeding episodes and severe infections.

The abstract includes results from integrated analysis of 17 boss patients, including the complete dataset for the eight patients from the Registrational study and an additional nine patients who received rutile, one or three that's part of an expanded access program.

Patients will fall it for a median of three years in integrated data set with the first patient treated eight years ago, making this the longest published follow up of HSC gene therapy to your ability to date using lentiviral vector transduction.

Well no adverse events consider to be related to 80 or one or three no reports have been sessional oncogenesis.

This is a testament to both the durability of effect and also the long term safety that it's possible using this approach.

16, 17, 94% of patients were line for the time the analysis.

One patient in the expanded access cohort died as a result from an existing neuro degenerative condition that was considered by the investigator to be unrelated OTO 103.

All of the surviving patients successfully engrafted within three months, leading to an increase in fact, a copy number I didn't was protein expression in different sold in Egypt is that has been maintained for up to eight years.

Nine months post treatment all patients were able to start receiving platelet transfusions and there were no severe bleeding episodes recorded.

Patients immune function also improved but all patients discontinuing hemoglobin supplementation post treatment over time and experiencing a reduction in severe infection rates also just oh effective immune reconstitution.

In summary, these data show correction of the two major life threatening aspects of the disease.

More complete analysis will be presented in a poster at ash in December .

Now, let's turn to the abstract freight is good.

We are presenting data from 30 patients that is the 20 patients from the fresh formulation Registrational study and supportive data from an additional 10 patients treated with a crime Brazil formulation.

You objectives this dataset with two fold.

The first was to show that the cryo formulation perform similarly to the fresh.

Analysis of both effect to copy number in grinding ascites measurement girlfriend, and Cdthree T cell reconstitution, a relevant measure of immune recovery should a consistent performance across the fresh I cry preserve treated patients.

Overall results showed engraftment of genetically modified HSC 29 of 30 out you'll want to one patients within approximately six months of treatment, which persisted through the follow up period and both datasets.

One of the patients receiving the cryopreserved formulation fail to grow and subsequently received as rescue allogeneic hematopoietic stem cell transplant or HSC teeth.

We have looked into this engraftment failure and have no reason to believe it was related to the formulation virtual one or one that the patient received.

This data is consistent with the MLP crime dataset presented at U.S. TCT last month.

We and our partners have now treated over 40 patients with chronic preserve gene therapies on a consistently seeing similar engraftment results between the crime and fresh formulations across the portfolio.

The second broader objective was to evaluate the 30 OTO one on one patients clinical outcomes Wassa historical control of 20 680, a skilled patients receiving allogeneic HSC team.

OTO one on ones compelling clinical profile remains in place with 100% overall survival was 88% overall survival for patients receiving HSC tea.

Event free survival was 97% for it you'll want to one whereas in the historical agency T. control population.

40% of patients were quite a second rescue HSC Ti or returns yahtzee, who passed away in.

In addition, eight patients or 31%, receiving HCT had acute or chronic graft versus host disease.

At the longest available follow patients treated with the crime freezer formulation, which was 18 months five seven patients or 71%, reaching that time point I stopped it Mclaughlin replacement therapy.

This is comparable to the data at 18 months for patients treated with the fresh formulation and coupled with previously presents findings on b cell function illustrates the completeness of immune reconstitution, we are seeing patients receiving rutile, one or one gene therapy.

Again more data from this analysis will be featured in a poster at ash.

Finally, I'll touch on the MPS, one hotel two or three program.

An abstract was accepted as an oral presentations at ash.

Data from the ongoing proof of concept study was presented at S.S. I am and demonstrate to successful engraftment and all six patients treated.

Since enrolled a seventh patient into the study.

Preliminary clinical evaluation one year following treatment in the first patient showed signs of resume growth improve motor skills on a stable covenants of school as well as evidence of metabolic correction.

This trial is close to completing enrollment of eight patients and proof of concept data is expected in 2021.

That wraps up my section, we're looking forward to seeing many of you had asked and keeping you updated an old exciting developments sort of what you are.

I'll now turn the call over to Frank.

Thanks.

Thanks, Bobby and let me add my welcome you can find the full financial results for the third quarter in this afternoon's press release, which I will briefly highlight here.

We ended the third quarter with 366 million in cash and investments and hope to an additional 50 million available under our credit facility.

This strong balance sheet will allow us to execute on several key milestones without the need to access the capital markets, including regulatory filings potential approvals and commercial preparations for multiple global launches.

System with half guidance, we expect that our existing cash investments.

Will fund, our anticipated operating and capital expenditures into the second half of 2021.

This runway does not include the capital available under our credit facility or proceeds from monetizing any priority review vouchers, we may receive upon the U.S. approval for our programs.

For the third quarter 2019, R&D expenses were approximately 28 million, which are only slightly from the R&D expenditures for the same period in 2018.

We expect R&D expenses to generally increase in future periods as our programs advance through development, though there may be some lumpiness in particular quarters.

SGN a expenses were approximately 14 million for the third quarter of 2019 compared to 8 million in the same period last year.

The increase was primarily due to higher investments to prepare for the commercialization of our late stage programs as well as higher cost to support public company operations.

During the third quarter, we recognize 1.9 million in revenue related to sales of through goes.

As the first ex vivo gene therapy approved by the European Medicines Agency Strimvelis isn't important source of learning for our commercial organization.

In in a minute Mark will talk more specifically about how we're leveraging that product to build our capabilities ahead of the next wave of launches.

We used about 53 million of cash to fund operations in the third quarter 2019, which included about 17 million in cash payments related to the licensing of our MTS one program in May.

Excluding this onetime payments, we expect our quarterly burn rate to grow in subsequent quarters to prepare for multiple potential product launches in next few years and begin to build out of our own manufacturing facility in Fremont, California.

In addition to our investment in the facility. We're also investing in multiple strategies to make our manufacturing platform and processes more efficient in a commercial setting.

Some of those investments are focused on new technologies, such as transduction, enhancers or a stable cell line, which could both have long term benefit of reducing the amount of vector usage per patient.

Our investment in our own manufacturing facility will enhance overall capacity and provide a source of additional supply along with our current manufacturing partners.

In addition to manufacturing, we're always looking for opportunities to enhance our portfolio and capabilities through focused investments in research or licensing deals.

This leaves us with several levers in the piano to manage our burn rate depending on the macro environment in which we operate.

With 2019 coming rapidly to a close we're pleased with the fundamentals of our business and we'll continue to deploy capital in a focused way.

I'll now hand, the call back over to Mark to close.

Thanks Frank.

Preparing to commercialize on a global scale is crucial to the success of our launches in M.L.D., an IDH Kid and our future gene therapies.

As Frank said.

Marketing stream Dallas, the first ex vivo HFC gene therapy approved by the European Medicines Agency.

Has enabled us to produce commercial supply and treat patients in a real world setting.

This involves a number of activities, including patient identification.

Understanding the logistics and support required for patients and families along that treatment journey.

Securing reimbursement for cross border health care delivery within the E U.

And completing the manufacturing and release process shed yield and tailored for each individual patient.

We treated multiple patients over the past quota demonstrating our ability to scale and deliver these therapies at one center.

This is preparing us for the time when our investigational therapies, if approved will be made available at multiple centers around the world.

To this end we have increased our global footprint with operations now established in North America, a growing presence in Europe , including the UK, France, Italy and Germany.

And plans to establish auction it in Latin America, Turkey, the middle Eastern Asia over the next few years.

We have hired leaders in key global commercial and medical functions, such as market access diagnostics Medical affairs medical information and patient advocacy to facilitate knowledge of and access to all therapies.

Finally, we have begun establishing qualified treatment centers in the first countries, where we expect to launch and putting in place a well controlled supply chain.

This includes a high touch patient support program.

Some of our gene therapies represent the first potential treatments for the diseases they are targeting.

This is driving new impetus in patient communities and with health care professionals to ensure affected diagnostic pathways for these diseases are in place for example, or she is working with multiple stakeholders to expedite pilots in M.L.D. newborn screening in both the U.S. and Europe .

With multiple potential one other kind approvals on the horizon.

Oh, it should could look like a different company by this time next year.

I'll call, we'll always maintain our commitment to putting the patient first and to be innovative across the entire company as we bring these novel gene therapy medicines to the world.

Thank you for your time and attention operator, you may now open the lines for questions.

Thank you Sir as a reminder to ask a question you would need to press star one on your telephone.

Your question press the pound key please standby what compiled acuity roster.

Our first question comes from with me.

Guggenheim. Please go ahead.

Hi, guys. This is on with all on forgive me so two questions actually.

But the cryo data now in hand, Danny a day rate limiting steps to fighting for anybody in that you.

Other than just getting that hit in the application and then your mind US can you. Please remind us on what is left to do or the U.S. filing.

Yes, thank you very much.

Question, I think when a great place with the M.L.D. file.

We've obviously got compelling data that's come through.

The integrated analysis that you saw earlier this year as well as the recent cryo data.

And so really our job now is to expedite the submission and well see working diligently to do that balancing both speed and quality.

We appreciate that in such a devastating condition the patients awaiting an everyday does count and you know well keep you posted this is clearly an important program for us.

Thank you.

Thank you.

Next question comes from kind of walk from Barclays.

Thank you for taking my question Congrats on a data update so I have two questions. The first why is regarding the one was 88 <unk> you did mention you know one a patient from the crowd data.

I did nothing glass that that was not related to <unk> product. Just wondering what was the reason for that patients the graph. It now happen in a way.

I do apologize for yet.

Yeah, maybe Bobby would you like to answer that one.

Yes, so the thank you for that for that question.

Just to just kind of set the context of this the so this is a the cryo study here is supportive data and will accompany.

Package that includes in vitro compatibility between cry preserved and fresh formulations of the or two on hotel one of one truck product. So it is supportive to that.

Having said that there will be a engraftment ideas and we do see even in fresh formulations Engraftment pages. For example in the context, all allogeneic transplantation with regards to this particular patients we have looked in detail at the drug product in the process on patient characteristics and we can't find.

Reasons pool.

In this individual and it may be relates to a patient specific factors and again just a for context, we've not treated.

Over 60 patients.

With OTO 101 and across the 60 patients. We just had I just a very small number just creek radiant and one of those studies was in a patient receiving a fresh cell phone connection. So you know these non engraftment I can occur either in fresh ore in crime present formulations and I'd say at the moment.

Well, thanks with those reasons are on it it's only happening in a very small minority patients.

Okay, great. Thank you and my next question is regarding the wells three <unk> to deal with one Daffy Kupol and he said well continue to generation.

Degenerative disease.

So just wondering if he can give a little bit more color when did that happen.

And that a related question on losses sat for the Cry formulation trial, just wondering if you can give us the status of the email me.

[noise], Bobby we'd like to analysts.

Yeah sure. So I just in a with regard to the patient who was treated.

It's a huge who died in the in study a unfortunately and type operation was an expanded access program.

Patient and he died four and a half months post gene therapy and came into the gene therapy procedure with an underlying neuro degenerative condition, which unfortunately, he succumb to and it was nearly desktop to offer the procedure.

So that's.

No it's not patient I'm sorry, the second part of your question was.

Cryo study hasn't yet the cries study has started and has started to enroll patients.

Okay I'm just wondering if you can give additional color acting at the guidance a complete enrollment in first half 20, Alan just wondering if you can give additional color like how many patients already.

So we I mean all patients.

Go ahead.

Yeah. So we've had for patients that have been treated so far and the you know were pleased with the progress about and the recruitment that's ongoing.

Okay, great Yeah, maybe just to put the all in context, just recall that we've had both now the 80, a skid cryo data and the M.L.D. cryo data.

And that both showing that the.

Functioning in a similar way too to fresh and on top of that you think about transfusion dependent beta thalassemia well. The MPS. One programs. These are just already initiated using cryo, we didn't think there's anything.

That's different it's just that we're proving for these first three programs it happened to be initiated with fresh.

Cryo is watching in the same way, but there's a large body of evidence now when I think at around 40 patients just in our portfolio that the being treated using cryo so far.

Great. That's very helpful. Thank you.

Thank you.

Next question comes from.

JP Morgan. Please go ahead.

Hi.

How far on the call Tonight.

Thank you for taking my question one congratulations from ethanol progress, perhaps perhaps Q from Oklahoma number one the on a 101 on one of three program bumps in the summer at the Ash Abstracts. This morning, but I believe.

You can keep on my mind I don't.

The more marazzi that we should be looking out for specific on Washington, DC in patients with them that complete data fad.

And then I'll pull forward the question on WAF firming up of all types I want all Wadham squad pull my mind, often timelines for the rolling BLA submission are you still tracking towards the first half of my yeah, and I are there I'm dating back to complete a floor.

Matt I before you said my thanks, so much.

So I'll ask Bobby to address the first part of your question then I'll take the second part.

Okay. So as far as the data at Ash is concerned what you'll see that was just more detail on these two studies. So remember these studies of finished enrollments. So you won't see dates on any further patients, but you will see more detail on.

The drug product the patient characteristics.

A follow up in terms of back to copy number and all the functional I say slip, but that was costs and the 88 study, but the wouldn't be any for the patients.

And with regard to your second.

Yeah with regard to your second question.

One of the key steps was the cryo work, which were presenting Oh Wow. So it's a asked so I think that that's an important step in the whole.

CLA preparation.

The other one which we have mentioned before as a F.D.A. guidance.

We are working on process validation runs the drug product using patient material and that's another requirement.

For from the F.D.A. before we initiate the rolling B.L.A., which we're guiding to as we've already said the first half of next year.

Okay, great. Thank you for taking my question.

Thank you for the question.

Thank you next question comes from.

Hello.

Please go ahead.

Thank you for taking my question.

A quick ones I shouldn't valley.

How many patients did you treat this quarter and have there been any specific changes to from Dallas pricing reimbursement this quarter basis.

Earlier in the year.

Thank you the question, perhaps I can Oscar Frank to take that one [noise].

Sure I think the.

The number of patients treated in this quarter was a total of three.

And with respect to your second question you know the prices for imbalances has remained the same since its launch and there's no.

Plans for any changes there.

And then maybe taking I looking a little bit into the teacher can you you mentioned commercial preparation.

You help us understand.

Some of the details around that and the timing for the spend over the next.

Several quarters as you're competing to filings and maybe to position to launch in some markets in 2021.

Yeah I'm so.

As we prepare for commercialization or a number of things that were doing the first is establishing the commercial footprint. So geographically where here in the U.S. We are in Europe in key markets as I mentioned like the UK, France, Germany, Italy, and Progressive Lee, we will continue to expand off.

Oh print in advance of launch not just this year, but also over the next couple of years.

As I said before in our goal is to have a global commercial footprint. Because these are rare diseases patients need.

These treatments all over the world.

Within our footprint comes.

A number of activities that were undertaking to prepare for alone. So patient identification work is key and I think I in the call earlier I alluded to the importance of some of the types of work, we're doing such as helping expedite pilots for newborn screening for M.L.D. also expanding the 80 eights kidney.

Born screening that already exists.

As well as disease awareness generally which is I think another important aspect of dealing with rare diseases.

The other area were focusing on is you know there our sense is that we would like to become centers of excellence for the treatment of patients and so we've identified centers.

There are good at transplants, but also good at the disease areas specifically the were launching into so we know which ones. Those are my working to qualify those centers in advance of launch.

And then I think the final area just to call out as market access and I think.

Yeah, you know, there's a great deal of important work to be done with a whole range of stakeholders in advance of launch because we are talking about.

Extraordinary medicines that have the ability to transform a life in one single intervention and so we're really looking at the value proposition of each of our programs.

That represents to the health care system and to these patients into society, and we'll be able to articulate that very clearly a before launch.

So were also looking at flexible payment models.

In terms of how these can be paid for according to the compares needs. So I think there's a lot of different areas are working in and no. I think we're confident we can prepare a successful loan for our programs.

And how how would this spend.

Yes.

Accordingly.

Yes, I think I think we've we ended the year ended the quarter 366 million, which which gives us runway into the second half in 2021, I think theres going to be growth in R&D SGN, a and of course in capital expenditures related to the manufacturing built so all three.

I think we'll generally trend upwards, leading into the filings and potential launches. So so to answer your question, specifically I think SGN, a well trend upward as we get closer to launches.

Yes.

Sure.

Thank you next question comes from David.

From Wedbush. Please go ahead.

Hi, just a question it's as we look at your commercialization plans have you.

Your talk repairs and and talk with other folks on the durability and long term follow up the true.

On your studies on how that would relate to.

You know some of the installment base pricing that we've seen instituted or or planned for with other launches took a quick for five years, but obviously you have longer follow up in your studies so is that.

Central upside or you think this five your model is that is getting to be said and pairs mines. Thanks.

Well first he thanks, David for just pointing out an underlying the very important.

Fact that we do have such long as your ability to raise the.

And therefore.

You can argue that the uncertainty around the duration of effect with Eva hematopoietic stem cell gene therapy is lower.

To maybe other modalities, so I think it isn't real benefit of the way that were pushing Jeep Cherokee.

I think there isn't just a one size fits or Oh, that's your question.

It may well be that for some pads.

They feel very good about that data that they feel it is unnecessary to put in place.

I sort of burdensome follow up requirement of patience over an extended period.

But as I said and think that is a one size fits all I think it will depend there are many different types of pair that we're going to deal with and I think the key point is the west flexible and they're willing to operate a variety of different models. It's really the value. That's the important thing for us to align on and then I think it's a question of how do we best get it pay.

Paid for.

Thank you.

Thank you David.

Thank you.

Next question comes from.

Huh.

Please go ahead.

Great. Thanks for taking my question. So maybe a have a couple of questions on an aviation Kid and maybe the first one just give a sense too I think we have a good visibility now into falling in the U.S. and and certainly strong Bill. If you know is in the market in Europe , but what do you need to do to then be able to file with you may be your.

Our program and then secondly, you know maybe one who've notice is the new.

Patients coming on therapy is a bit lumpy. So I guess the question is how much visibility do you have to when patients coming onboard and are the numbers. So small because it's so selective by availability in different centers. Thank you.

Yeah. Thank you for that question I think.

As I mentioned previously that.

When it comes to prioritizing our regulate treat work.

We're really focused initially on countries around the world, where there is no gene therapy 80, a skids. So our priority is being you know the United States and then we're also focusing on other geographies.

Other parts of the World, where we think is important to bring first gene therapy medicine for ideas kids patients as as a priority but in parallel to that obviously, we have a huge amount of clinical and regulatory asset behind M.L.D. and Wallace and so on so I think in time, we will look to bring hotel one or one.

The European market as well, but it's not at the top of our priority list at this time.

As to the forward visibility Frank do you want to speaking I, just I mean in terms of Strimvelis patients you're right that it has been a bit lumpy him and remember theres been ongoing studies for OTO 101. During some of the time that's from Dallas has been available.

But you know candidly there are some limitations with streaming almost because you have to go to one center in Milan, and sometimes that does represent some reimbursement challenges. It is the only commercially available that's the wrong gene therapy for radio is good and so we are continuing to support behind the product and.

We think it as a great option for patients in need. So so I think the results that we've seen recently I think speak to our ability to deliver product commercially and the learnings that we get from that because it is about identifying patients. It is about securing reimbursement for those patients and then importantly.

The about manufacturing and releasing the product and we did that multiple times. This past quarter successfully so I think those learnings that we get from from those are going to serve us well.

As we move into launches for M.L.D. and OTO 101 here in the U.S.

Oh.

I'm, hoping that we can still online ties.

Yes, Sir.

Sure. Thank you question comes from Great Lakes Avanish fish from Goldman Sachs. Please go ahead.

Great. Thank you I'm. Good afternoon. Good evening, congrats on a quarter I've got a four questions actually I hope you can take them off them or quick.

My first has to do with some mark is there any update on perhaps hiring a new chief commercialization officer, I know that you've taken on some of the responsibility of them. So I was just curious as to what was happening there.

My second question just has to do with them business development activities and I know you recently in licensed and out the two or three program and just wondering what the appetite is to bring in either additional programs or perhaps look to a partner programs I don't think partnering Uh huh.

Part of what you're looking to do so if you could talk about that.

The follow up to that has to do with your the company's capacity to handle all of your programs you've got a lot of clinical programs and you've got some preclinical ones as well. So I was wondering if you could just talk about I'm kind of maybe the scalability of of how you can handle all of this and then lastly, you know the data around June .

Or cryopreserved formulations looks quite compelling in terms of the comparability with the fresh sell preparations and so I'm wondering if you could just give us some color and what's happening crops like behind the scenes to generate a necessary data.

Convince F.D.A. in terms of that Bioequivalent professor a term between the cryopreserved the fresh del preparation. Thanks, so much.

Great question, So I'm going to do my best remember all four.

The first.

About the Chief commercial officer.

Clearly for me personally, it's actually rather a nice movement to get even close it's the commercial side of the business having spent a lot of my career.

In the commercial side, and having launched seven orphan drugs. So.

I'm really delighted by the team we have in place I'm working closely with the team here and you asked as well as our European team in advance of these launches, but with regard to the the such as you can imagine we're getting a lot of interest in that that ROE because they're probably aren't many gene therapy companies.

With a three filings in the next two and a half years and launches. So the such is going well we have some great candidates, but in the meantime, my focus is to make show that we maintain momentum on launch preparations on both sides of the pond.

With regard to D. and capacity, perhaps you know Frank do you want to address those points yeah sure. So on business development. We've had a lot of success over the last couple of years.

Lenient programs into these three franchises that we now have today.

So so we have an embarrassment of riches at some level. We have now soon to be seven programs in the clinic and so the bar you know continues at higher with respect to any future in licensing opportunities. We've got a lot dinner plate and then we're excited about that and we've been executing well based on the achievement of all the milestones this past year.

Sure.

But you know if there are programs out there that can leverage you know our franchises and some of the diseases, where we are today, we will continue to be opportunistic about those but make sure that we remain focused on delivering especially in the near term on our lead programs with respect to the point about capacity obviously, we.

Built the organization to manage the various programs that we haven't and they're at various stages of development. So as you can imagine.

Depending on the stage of development different resources get pulled in.

To to move the programs through development. We have you know a team assigned to each program. We have a program lead for each program and they're doing a great job you know.

Advancing the program, so I feel like from a resourcing capacity.

Perspective, we're in a good place.

And again, that's that's one of the bars that we set for ourselves when we look at new programs is how much additional resource will need and we'll have leveraged supply from that we've already built.

And then but they would you like to taste. The question about the prior formulation theater and also our regulators we sort of step two.

To meet the regulator needs in this domain.

Yes so.

So well not we have engaged with the the regulation in quite some significant detail to understand what they would like as far as thick compatibility between fresh and crime is concerned then really they're out there are two elements to that one isn't in the true CMC.

Compatibility package, which is looking at the two products the fresh in the formulation and then looking at a number of different parameters.

Between the two and so those promises and include.

The total number of critical points to sell that pure see the viability of those cells that back to copy number the activity within those trends do cells right in the case, Oh Gee I want to one so those parameters or they are equivalent between two.

And then a this would be supported by.

This will be supported by data from some patients that I've received the crop is information about the data that we've shown you want to one it's the data that we've shown you in MLT already and that data suggest that the the crop is a function is working in the same way as the fresh self formulation. So it's a combination of patient well to date.

With the in vitro CNC compatibility.

That's great. Thank you so much for answering my questions.

Thank you Greg.

Thank you.

I shouldn't further questions in the queue at this time I like to turn the call back over to Mark Rothera, President and CEO for closing remarks. Please go ahead.

Well. Thank you all for joining the call today as I hope we demonstrated our momentum continues to build as we approach offers to regulatory filings. Whilst we're also advancing a rich portfolio of clinical and preclinical pipe a program.

I'm really proud of what the team has accomplished this year, when making great progress towards our mission of bringing potentially curative therapies to patients around the world.

And if approved we believe these therapies have the potential to provide a lifetime of benefit to patients in a single administration, which is a remarkable thing in the world of medicine.

Thanks, again, and we're looking forward to seeing many of you next month at Ash. Thank you.

Ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect today.