Q3 2019 Earnings Call
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I would now like to turn the call over to Andrew Chang head of Investor Relations.
Please go ahead.
Thank you operator, and good afternoon, everyone.
Just after market closed today, we issued a press release with earnings and operating results for the third quarter 2019.
The press release, a live webcast access are available on the investors and media section of the dentist website at Www Dot dentist T X dot com.
The webcast link will be available for approximately 30 days.
Joining me on the call today, or Matt Patterson, Chairman and Chief Executive Officer.
Natalie Hollis, President and Chief operating Officer.
And Tom Soloway, Executive Vice President and Chief Financial Officer.
Before beginning with prepared comments I'd like to remind callers that the information discussed on the call today.
He is covered under the safe Harbor provisions of the private Securities Litigation Reform Act.
I caution listeners of the company's management will be making forward looking statements.
Actual results could differ materially from those stated or implied by our forward looking statements due to risks and uncertainties associated with the company's business. These forward looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's LCC filings.
The contents of this conference call contains time sensitive information is accurate only as of the data Thislife broadcast November 7th 2019.
Hi, dentist undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of today's call except as required by law.
I would now like to turn the call over to my Patterson, Chairman and Chief Executive Officer.
Matt.
Thank you Andrew and good afternoon, thanks for joining us today.
We're pleased to share with you. The recent progress we've made across our product portfolio.
Well the several important key milestones were looking forward to us because here.
Beginning with our lead program 80, 132 for X linked to my tubular Myopically or X L. M T M.
We were pleased to present updated positive data from a spiro at the recent world Muscle Society meeting in early October .
We were particularly excited to report that the first seven treated patients all six treated patients in cohort one and the first patient treated in cohort two are now ventilator independent.
And for patients are not walking independently or with support.
These outcomes and stands in Stark contrast to the natural disease course excellent yeah.
Feedback from our treating physicians in Cana wells continues to characterize these clinical benefits is unprecedented in the field neuromuscular disease.
And importantly, 80 132 continues to be generally well tolerated with a manageable safety profile across both of those cohorts.
Turning to the pivotal expansion cohort first barrel I'm pleased to share that as part of our patient identification efforts, we were able to identify two additional patients who met the study criteria, bringing the total planned enrollment to 10 patients or five age mass treatment and delayed treatment control pairs.
We expect it eminently complete enrollment of the final patient and as a result remain on track to send it to be alliance United States mid 2020, and M&A in Europe , and the second half 2020.
And with that I'll turn the call over to not only to walk through our recent progress on the rest of the pipeline Natalie.
Thanks, not and Hello, everyone.
I'll start with an update on our Pompey program and an overview of our differentiated approach to AB based gene therapy for this disease. As a reminder, we believe that 88 four or five is the only gene therapy in development today, which is delivering and expressing G.A. directly in the primary tissues affected by the disease.
Both enzyme replacement therapies and Liberty directed gene therapy candidates rely on an inherently inefficient multi step cross correction mechanism to achieve achieve the intended biologic effect first GE must be delivered into the bloodstream.
Either via exhaustion of confusion or an internal liver based pump then circulating G eight needs to be taken up from the plasma into the myositis and then properly traffic to the lysosome, it's needed site of intercellular action.
From a competitive perspective, the liver directed gene therapy approaches must engineer that transgene to attempt to improve the efficiency of this cross correction, but there's also creates the potential for neoantigen induced immune responses to this non native version of GA. In contrast, our approach delivers an expresses wild type GA.
Directly where its naturally active which we believe will result in higher levels of GE, a expression and activity in the key muscles that drive Pompey disease pathology and an overall superior therapeutic profile.
With respect to our Pompey development candidate 88, four or five we recently achieved our stated goal of submitting me I Andy at the end of the third quarter. The FTC review of our submission is ongoing and in parallel we are progressing or clinical trial sites start up activities and anticipation of starting our phase one two clinical study in the first quarter.
The next year to that end, we are initiating a screening study with our U.S. trial sites to accelerate patient identification for a moment into the phase one two study.
It's also important to note that we have already completed GMP manufacturing to supply the entire phase one to study the design of which we expect to share in the next quarter ahead of the study start.
We also plan to share Nonclinical data on 84 or five at the Worldsymposium next February and look forward to keeping you apprised of our progress with this important program in the coming months.
Turning now to our Duchenne muscular dystrophy or DMD programs. We're excited about the significant progress we've made with these programs as well during the quarter.
As a reminder, Indian D., we're advancing a platform approach to Dr. rise exon skipping in which we are utilizing a single use seven SNR in a back then construct combined with unique dystrophin Exxon targeting oligonucleotides sequences to efficiently advance development candidates for multiple DMD genotypes and pair.
Hello.
To that end during the quarter, we held a productive face to face meeting with the FDA to discuss our proposed approach to streamlining the nonclinical CMC and clinical elements of the overall development plan.
Very pleased with the agencies level of engagement and the overall tenor of this initial discussion and importantly, we gained general alignment on our proposed next steps for the program.
For 87 owed to our first product candidate utilizing the platform Dr. Han dose ranging and toxicology studies are progressing well we remain on track for an eye Andy filing in the first quarter of next year and plan to initiate clinical study in the second quarter.
With the second candidate 87, 53, we've selected our Exxon targeting oligo sequence and manufacturing is underway to support <unk>, enabling studies to be initiated this quarter.
And 87 51 is following closely behind with all the good sequence screening underway and I, India, enabling studies expected to begin next quarter.
As a reminder, we believe that together. These first three factorized exon skipping product candidates have the potential to address more than 25% of the duchenne patient population.
And also importantly, as with both excellent T M. In contact we expect to initiate our clinical program utilizing our commercial manufacturing process, which we believe will provide a meaningful competitive advantage in terms of the speed with which we can advance through clinical development in DMD.
And our Myotonic dystrophy program, we continue to make progress with our constructs screening studies for 80 466, utilizing both DECT rise R&D knockdown and vector eyes exon skipping approaches.
We look forward to sharing data from this program next year and remain on track to submit an eye in D. and 2020.
We're excited by the potential of this program given the sizable patient population high degree of unmet need and the uniqueness of our approach, which leverages, our avi manufacturing and neuromuscular expertise to provide a potentially transformative benefit for this devastating disease.
Turning to manufacturing we were pleased to report their process performance qualification or P. PQ campaign is well underway and our facilities pre approval inspection activities are readiness activities are on track to support the 81 three to be L.A. filing mid next year.
And our plasmid facility, we completed all of our GNP readiness activities last month and expect the 87 or two clinical campaign to be the first to utilize GMP manufacture plasmid manufactured in house.
We continue to view, our investment and end to end internal manufacturing as the cornerstone of our strategy for delivering our important therapies to patients and creating long term value for shareholders.
Finally, we continue to maintain a strong balance sheet with $351.5 million of cash cash equivalents and marketable securities as of September Thirtyth 2019.
Our balance sheet strength positions us to continue to make meaningful progress across our pipeline.
We're excited by our multiple upcoming milestones and look forward to keeping you apprised of our work over the coming months.
That concludes our prepared comments for today's call. Operator, you may now open the line for questions.
Thank you as a reminder, chaska questions. Please press Star then one on your touched on telephone withdraw your question press the pound fee based and Bible, we compile the culinary roster.
Our first question comes from Debjit Chattopadhyay from H.C. Wainwright. Your line is now open.
Once again, our first question comes from Debjit Chattopadhyay from H.C. Wainwright. Your line is now open.
Sorry, I was on mute.
Good afternoon, guys. Thank you for taking the call.
So my question is on the population that would be a minimal to treatment for the pump. They oh I'm sorry for your excellent in programs. So I do think basically that there'd be upper limit.
Each of which you would expect to see a clinical benefit perhaps it is excessive muscle fibrosis.
Hello.
<unk> as Matt. Thanks for the question Oh I'm sorry. This is.
This is Aaron Entre Debjit I forgot to.
[laughter] I didn't hear that.
So thanks for the question.
We've talked about a few times over overtime Tim's really unique muscle disease. It is not suffer the same degree of thought inflammation scarring and progressive damage. The once he's other neuromuscular diseases like to show.
And so.
We've always had optimism built days, our preclinical work that we'd be able to treat patients across the spectrum and show a benefit and sure enough you see that represented in our study where we've shown no dramatic improvements in kids and ranging in age from nine more to six years.
So we continue to have a great confidence that even in children.
He is for a number of years.
Can produce benefit was this approach.
And that being said, that's that's something that we will continue to explore and are considered a investing very soon and that additional clinical studies that will explore safety and efficacy and slightly older patients. So that's something that's top of mind for us and of course, we think about in terms of commercial as well and ensuring we have the strong story.
A couple to achieve reimbursement across all patients with them to him so more to come on that but in general biologically in particular, we're confident that all NTM patients can benefit from this treatment.
Okay. Thank you and on your plan for DMD and pump a so the plan is ultimately to use the same.
Maybe a sector I know you guys had mentioned before you were going to initially use that and CH 89, and then transition Davey so.
Based on the a high amount of vector genomes for nyquist. They are at the when these 14 for Threed 14.
Pilot genome doses would you anticipate a similar dosing.
For DMD in Palm Bay.
And a similar promoter.
Well, what do you think positively.
Well, we're certainly a continued to be committed to 88, we think its serotype that has shown a tremendous potential and the MTM program of course, so in both programs I pay into Shan, we'll be using aviate again.
As far as specific doses and promoters in such a there's definitely differences program to program and we look forward to sharing more and so on that when we have a pumping clinical discussion after getting stuff do you guys. A review of the I'd and similarly on Duchenne.
But I would just say that in our experience and this is one of the lessons learned over the years and multiple indications is that each of these diseases is different in its own ways.
Routine you're replacing each case is different in its own ways and you really have to work to figure out how best to apply the science and so we've learned a tremendous amount of and feel extremely positive about where we are with okay and our next steps in that program and then similarly with to shine, although of course, but to shine as you know.
It's a different scientific approach factorized exon skipping.
But nonetheless, we apply a lot of good lessons learned in our preclinical work.
Set ourselves up for success in both cases.
Okay. Thank you, Matt and congrats guys on Florida.
Thanks.
Thank you. Our next question comes from Joseph Schwartz with SBB Leerink. Your line is now open.
Good afternoon. Thanks for taking our question. This is <expletive> on dialing in for Joe Congrats on all the progress I had a question on DMD <unk> platform strategy and then a question on pump pay so.
That's true DMD Matt.
On the prepared remarks, not only talked about having a discussion to face to face discussion with the regulators, but I was just wondering if you could maybe elaborate a little more of what came out of that discussion. So specifically I'm wondering.
I wouldn't ideal development course looks like based on this platform approach I mean, how much of a truncation and timeline we anticipate.
<unk> seems to be onboard with this idea and then in terms of Hum Hey, it's actually more of a two part question, but not a we're waiting on 84 or five in Pompe disease are obviously multiple agents that are either in the clinic, where currently approved so just wondering.
Where do you wouldn't necessarily see 84 or five addressing the most in terms of treatment landscape. Since we have standard of care Nexgen, New York cheese as well as Lentiviral.
Hey, I'm drugs in development and then secondarily as we think about the trial design process, we're a little early here, but.
I guess is it fair to assume that it's more of a phase one two or with a long term fall off in safety that could get you to the finish line or is it more of a traditional development phase one two followed by a phase three trial.
Sure so often they're a big on thanks for question and I'll start now it's not only to to jump in but you know on a pump had we not only started in her opening remarks, and it's really really important to highlight once again and that we strongly believe that these specific scientific approach we are taking.
We use a promoter that focuses expression in the muscle in the tissue affected by the disease, which can be contrasted with the liver directed techniques.
We'll be the superior approach to helping these patients in the future and we they said on.
A lot of our own preclinical work as old as well as their own evaluation of the entire landscape. So we still feel very strongly about our approach as being an optimal.
For homepage gene therapy, and so we're extremely excited to move into the clinic or linear and get that started and and show that has not only mentioned, we're looking forward to sharing the preclinical data that we have created four or five at the world meeting in February we know that people than looking to know when we would sure that and so we're happy to confirm that today. So.
As far as the clinical plan you know for pumping today I think what we can comfortably say is that what we've been saying for while which as we still expect to start in adults who are on ERP.
And that we will do dose ranging and with a focus initially on biopsies and in particular looking at expression levels of D.A., finishing protein.
And that overtime the program would mature to undoubtedly include a winning people off of the RT and evaluating their progress overtime as well and expanding the program from adults to infantile pumping in a separate study.
And that's certainly a all going happen as fast and then in parallel as possible for us.
I'd, rather not speculate on what it might take in palm pay to get all the way to approval I think that's a little early we should collaborate with you have today on that I'm, sorry, I do think that pump a clinical development is a bit more complex than what we've done an empty I'm just simply because you've got adult population in enough in top population in particular, so, but we have a lot of pumping experience.
Other rare disease companies around the table so.
We feel very confident that we've got Oh plant in mind.
So that's I think hopefully addresses pump they will afford us very little more detail clinical plan or full detail in the whole planned one stuff to come.
Completes review I mean, I Indian and we have their blessing to before.
On the do shot maybe I'll hand off to not only to let her.
Answer your questions I don't.
Happy to Heidi gone so as I mentioned, we did have a really productive face to face meeting with FDA a in September to talk through some of our thinking on this platform approach in Duchenne and never really three buckets of development that we covered a in the discussion or not.
In clinical development, so what would it take it get too I. Indeed for the first and then subsequent development constructs manufacturing and then what could some streamline clinical development thoughts looked like potentially on me at the Nonclinical. Aside we got good good alignment on the plan, which we've shared.
Previously, which has to do a robust I, India, enabling package for the first construct 87 or too and as I mentioned those studies are well underway and we're on track for the I need to be filed in the first quarter. Then the idea is with subsequent constructs we can leverage the a the dose ranging and toxicology.
Study data that we generate was 72 to put for smaller packages for future Andy's and we would expect that over time, the as we accumulate a bigger body of data on how the platform behaves those requirements will go down further with subsequent constructs on the manufacturing side.
It's really a discussion of the fact that the manufacturing process is essentially identical for each of these constructs. The only thing that changes from product to product is is one of the plasma. It's in our two plasma transient transaction system and said, we talked about ideas for streamlining analytical development process characterization that leverage the fan.
That we have this robust well established manufacturing process at this place.
At this point and then on the clinical side, we talked about ideas for a ways that we could potentially share safety database is share control groups across different genotypes and so that were earlier on on the clinical side because that's of course, a little further off from a from the work that we're doing preclinically and in many.
Sure and right now, but I think in general.
The agency was really excited about the approach they recognize the need to innovate not only in terms of the technologies that the design of the clinical program or the development programs to advance. These novel technologies and so we're we're encouraged and you know as we've said before we believe that this is a best in class approach to do Cheyenne that producing full length or.
Near full length versions of dystrophin are going to result in an ultimately superior product profile.
Excellent if I can just squeeze in one more question on DMD.
I guess, the some of the micro dystrophin players are.
Going through some dose related toxicities. If you will so if you can comment on deals that you may have seen and.
Clan studies, if you have.
And then secondarily I guess, that's worth thinking about those are obviously older patients.
And so on a systemic dose basis I would imagine the total viral load would be higher. So how are you thinking about perhaps capping <unk> in terms of inclusion.
Bodyweight inclusion criteria for the DMD studies.
Not too.
No not only once once you keep going on you shouldn't go ahead.
Sure I'm happy to so it's it's really too early to comment on inclusion and exclusion criteria for our addition program.
You know I'll say this we've got a good body had experience with high viral loads a in our NTM program. The fact that we use aviate consist consistently across our programs allows us to leverage our existing body of data on bio distribution and safety of the cap said and so that's one of the things that.
We believe is really going to allow us to accelerate and then in terms of dose limiting toxicities as I mentioned the Tox study on 700, she was underway, but I think one thing that it's important to remind you out of is the fact that this is a fundamentally different mechanisms. So we are delivering in SNR in a that is going to repair to.
Shifting endogenous dystrophin transcript, so we aren't overexpressing dystrophin and so you really your your theoretical a ceiling on dystrophin expression is 100% of wild type here and so and the other thing that's important to note is that this is only active wear dystrophin is naturally expressed so we think that.
Safety profile. This approach versus you know in some cases super because physiologic a expression levels of synthetic version of the protein has the potential to be a meaningful advantage for our approach.
Great. Thanks for taking my questions and look forward to your world.
Thanks.
Thanks.
Thank you and our next question comes from Chris Raymond with Piper Jaffray. Your line is now open.
Thanks for taking my questions just a few so first on on 81 32, So just looking back at the if the data from world muscle.
I mean, obviously impressive data, but that patient 12.
Who I think had.
Not seen a reduction of ventilator independence at week 20.
Just given that outcome and you know you've seen some variability overtime and I and it was kind of heartened to hear that Youve increased your your patient size for the pivotal to five patients each but.
You know you're gonna have are arguably some variability I guess and ventilator independence and with that endpoint of reduction over placebo of I think it's six hours at week 24 can you just talk about comfort level.
Given that you've got some variability as seen in that world muscle uptick. Thanks.
I got some follow ups.
Sure Hey, Chris It's Matt.
I appreciate the question a you know look I think it's a little early to draw any conclusions on patient 12, we look forward to the upcoming data updates with him and filling out that story. So I would encourage folks are not read too much into what we had to say a world multiple in that specific case.
But certainly what you're talking about generally it's something that we put a tremendous amount of thought into a you know, we obviously want to accommodate with our physical expansion plans all the agency feedback that we could.
But you know even on the on the numbers, we wouldn't have put together that plan.
We didn't feel comfortable that even given some variability you might see vision to patients that we would hit remarks.
And we feel strongly that we would do that with eight and it's even better to build out temptations, which was an opportunity opportunistic decision we made to expand the cohort given the patient I'd success, but Oh. So you know I guess, all I can say isn't that we're highly confident around the whole as a as we go forward about plan and.
Looking forward to it next steps ensuring those data when we get them a.
Next year.
Got it and then on pumping trying to make sure I understand the dialogue with FDA. So.
Your press release says the applications under review, but just.
Backing through the calendar sounds like you might be outside that 30 day window traditionally where the FDA accepts the I. Andy can you talk about that that has the FDA accepted the idea or is are they treating this application a little differently.
So it's a good question and you obviously right on the calendar we submitted a late Q3 and it's really very simple actually on day 30, The agency called and said we're sorry, we're busy we haven't finished.
And so it's really that simple we haven't really received a any meaningful feedback and they specifically said they need more time. So we expect the deltic. This extra 30 days, which is not a foreign concept to US first of all we know they're very busy and so we knew that there was the possibility this could happen obviously world.
And for 30 day clearance, but but recall if you know the story our story.
From last year. The same issue came up when we filed our CPV T.I., Andy and at the agency just didn't get to it and then 30 days later, we got some simple questions that we responded to 90 cleared. So you know so until stuff and so we remain really confident on the R&D is very strong package and has now they said in her comment.
All the clinical work is happening all the sites startup activities are happening all the screening study is initiating and so our guidance remains that's a study is going to start in Q1.
We have a high degree of confidence about.
Great. Okay. Thanks, and then if I can just sneak one more question in a seven no to I think last quarter, you guys talked about nch, starting dosing with their own construct in Q4.
Is that still the plan or I see you guys mentioned going ahead with with your construction in Q1 of 2020, just is that still the plant or is there or is that has that been changed a little bit.
Sure sure what Natalie once you take alone.
I'm happy to Hey, Chris So and you're absolutely right, we had been expecting nch to filing <unk> file there I, Andy and just the patient this quarter, you'll recall that the FDA had asked for a more robust tox studies since they had been at a pretty skinny package. The first time around that studies.
Fleet looks great and Nch is in the process of putting together the idea what you can see those at the time lines on the programs are converging and we're now almost on top of each other in terms of the timing for the I Indy filing. So we're working with Dr. plant again to sort of harmonize the timelines and the approach.
And and it remains to be seen whether we'll end up seeing a patient this quarter with his with his nch construct or not I think the important thing to focus on is not the that the registration construct if you're the one that we I expect to move through.
Clinical development and serve as the basis for the entire platform approach to Duchenne is our eightys domino to and that the robot I'd, enabling work that we're doing there is really what we're focused on its frankly, what you should be focused on on and well, we'll keep you posted as as our discussions with Dr. plant again in the group.
That nch continue to evolve.
So I mean, I guess, what I'm getting it there is this what I was assuming is this years was perhaps.
In the leader read on top so that would want assume then that you could avoid the number you know bridging activities that were formally contemplated.
Yeah, you know actually as a reminder, we did not too we decided not to take a bridging approach. So because we wanted to hit a robust I'd package around seven or too because it. It has the new backbone <unk> if you will.
The work on on a the dentist contract has proceeded in parallel with leading that the legacy work on on Dr. Flanigan's construct and you know it was an obligation that we knew we were assuming when we entered the the collaboration with him. He also knew that we wanted to refine the construct and make it on a better products.
It can serve as the basis for that for the platform and so really at this point it. It's it's a it's a matter of timing.
Got it thank you.
Thank you and our next question comes from other Palm Rama with Jpmorgan. Your line is now open.
Hey, guys.
Thanks for taking the question.
Can you and I'm, sorry, if I missed it can you might as the of the number of sites that you're targeting for the pump HAE program and how we should be thinking about pace of enrollment, giving you kind of already actively engaged with sites and if there's a chance that we might see some initial biomarker type of data in 2020. Thanks so much.
Hi out of home thanks for the question.
I think the team has finalized the exact number of sites that are going to be involved in the program, but we're off to a great start it's a than I really I think fun few months for the company to go out and interact with the various sites that we know well that have pompei expertise that participations.
I can say really comfortably that the reception has been extremely strong I think people appreciate the quality of preclinical data that we've shared with them and the nature of our approach how contrasts with others sort of a high degree of enthusiasm to be a part of the program. So will clarify the exact number of sites as soon as we can but but certainly it will be enough side.
To drive enrollment.
At a rapid pace I'm sure we'll start in the same sort of.
Stage manner, just to monitor initial safety like just about every trial our space.
But all the patients we feel really good about patient identification and as a Sallie mentioned script to we're starting the screening study.
Which will really facilities are getting patients lined up so much like MTM and and stuff to study kinda queuing up patients for the trial, we're doing something similar here so.
It will move quite rapidly.
Great. Thanks to kind of question Oh, I Didnt answer your question about about data I think.
Based on where we are today, then based on our expectation that will start the study in Q1.
We are sitting around assuming that we are likely to get to proof of concept data in the second half of 2020 at least initial proof of concept.
Would be largely a safety data of course, but also biopsy based information.
What exact numbers and exact amount of data obviously, we'll have to refine overtime, but that's our working assumption and that's part of why we feel so excited about 2020 I mean, we're staring a year ahead, where were filed delay for MTM, we're going to start a clinical trial and pumping and get to proof of concept data. We're gonna start a clinical trial into Shannon hopefully also.
Get the proof of concept data.
Well it I'd for Myotonic, so it's a year of tremendous momentum across the pipeline that were fired up for.
Just as a clarification you said proof of concept for for two programs pumping and DMD.
Hey, you know we feel it's gonna start early in the year and so.
We feel good about that but again I want to.
For confirmed that a little more later certainly after we get after years of blasphemy, I'd, which we expect to FID on but as we see the study can get started and I can confirm exactly how much data.
Well the timeline sit today, that's very reasonable.
Duchenne as not only mentioned the on track for Q1 I am D.. So one would expect a study started Q2 and so again, even though it's a little tighter its three months later or so on the timeline or it's not unreasonable to assume that we could get to preliminary proof of concept data there as well I'm not just safety, but biopsy based data that I think could be quite cups.
Selling.
To continue to tell the scientific story about why we feel or person to shine is gonna be superior.
Great. Thanks for taking my questions.
Yeah. Thanks.
Thank you and our next question comes from Whitney Ijem with Guggenheim. Your line is now open.
Hi, This is I've been on for one day. Thanks for taking the question I'm just question on excellent.
You're talking about kind of steps, you're taking precommercial, it's got ready.
Fair for commercial readiness.
Maybe on kind of identifying patients.
Fresh repairs and thought the pricing.
Sure. Thanks Evan.
It's very active you know, obviously natalee spoke to the program status and or we both it and they are manufacturing work and all that to get to the delay and be ready, but the commercial team has grown.
As you May recall, we started the year hiring our chief commercial officer, and he's done a wonderful job of a building out his team and.
So it's an area of great activity.
Good idea is absolutely a one of the top priorities and I would say that's going well I mean, we had historically done pretty well trying to.
Fine patients and in particular in U.S. in Europe , but they really expanded on that was added resources and so we feel good about that and that's going to be an ongoing thing, though you know it's rare diseases you always oh. It always takes time to find all these patients and of course progress in the clinic and eventually an approved product I go a long way to motivating people to help find patients but.
That's certainly a focusing going well.
And you know and your other point is the other key area of focus I would say.
And preparing for pricing and reimbursement discussions with payers.
It's something that we obviously take very seriously we've worked hard over time to to build a background story about the burden of living with M.T. and that's been pretty powerful stuff that we've continued to collection and look forward to share and going forward, though the burden of not just living with disease with the cost of living with the disease.
And so we're really building out that story and preparing for future conversations with payers of course, the clinical data is extremely powerful when we're going to be able to walk in there and talk about kids all of sudden hitting milestones they never had been coming off of ventilators.
So I think we're doing all the way work the clinical work clinical data supports it and so it's going to be a very strong story, but we we realize it it's a really important and complex ones. So that's why we're doing a tremendous amount of work early on.
And of course, we're learning from others and there were monitoring space and then seeing how some of the creative approaches that other companies in our field are approaching how to best commercialize these products given that we still currently live in a system that's not world not so well prepared for single one time here.
It is therapies.
Thanks, I think there's a lot of momentum in that area as well and we're in the sick of that so.
I'd say, it's off to a great starting it will be something that we really build on him 2020.
Okay.
Follow up on the I'm just wondering.
Kind of based on your interactions.
So Jim.
This is thinking a little bit different way for my for what might be required for approval in DMD post gorgeous and.
I mean, any changes and kind of feedback or.
You did not wasn't really the nature of the discussion we had we weren't talking specifically about endpoints that we would need to include for registration in Duchenne. It was more about the overall design of how do we efficiently address multiple genotypes unparallel on so it was really more of a question of study design and points I think it's little too early yet to tick.
Comment on registration endpoints for Dewshine, but of course one of the.
One of the valuable things about being where we are is that we we're keeping a close eye on the rest of the field and learning from others in terms of of endpoints and also actually doing a lot of a internal research on our own looking at novel ways that we can we can measure efficacy a in duchenne beyond sort of the standard.
Metrics that are used now.
Okay.
And can you give anymore is there any more detail you can give on the undisclosed partner in DMD.
Oh, the undisclosed academic partner on some 51 in some 53.
Yeah.
Yeah, we haven't we haven't said more publicly about that to date I'll say that the work is ongoing and it's a great collaboration we're really excited about it but we haven't shared more publicly so far.
Commercial underscores crush partner and give new as well or.
No we retain global commercial rights to all of our program.
Okay. Thank you.
Thank you enter next question comes from Ritu Baral with Cowen. Your line is now open.
Hey, guys is it to shut down for two thanks for taking my question. It's true to for me. The first one is the thing moving forward just give a sense on capex spending on manufacturing. It just seems like the current facilities are enough as you move into commercialization for excellent Jim and then also the pump and Dnbi programs that are coming up.
Sure I can start and you know Tom if you want to chime in a that'd be fine I mean.
The most important thing to remember that we've done extremely well with our manufacturing process and improving it overtime and so the current capacity.
And our two 500 leader by reactors that we manufacture in ourselves San Francisco facility is enough capacity to serve the global commercial demand for MTM as well as the near term clinical development.
Pompidou Shannon Myotonic. So we're in great shape, right now and so there's no urgent need.
For a big capital spends are some spend necessary I would say to get to a licensure I'll just some basic things with the facility to make sure that its and tiptop shape for inspection.
But otherwise nothing major that being said of course, we have an eye for the future and we plan on success for all these programs and so I think at some point reasonably soon we'll have more information on our plans for how you're going to go out expanding capacity.
Which we will need to do to accommodate of course, a future commercialization of pumping in Duchenne and so that's a work in progress and record sharing more in Philadelphia.
Okay. Thanks, a quick question on the DMD and just thinking about the fuel to fall in the multiple clinical trials and going right now I'm wondering how users thinking about.
Just to enrollment into the trials are in forward any concern for possibilities with finding patients more some of 51 53 by pushing them.
On to your choice.
Sure I don't know unless you want to talk a little.
Yeah I can start there. So we're starting with a 87 no two which is addressing a duplications in x. onto our me to Andorra mutations in exxon's when the five that's there actually is mutations are actually outside of the inclusion criteria for the micro dystrophin studies and so we don't expect to have any issues. There and then one of.
The important elements of our clinical strategy is to generate data as early as possible demonstrating the differentiation of our approach demonstrating that we can we are producing full length or near full length dystrophin and about preserving a superior functionality of this important structural protein and we think with those data in hand.
Going to be on we're going to be in a very good competitive position in terms of patient recruitment and you know where it's similar to what we're seeing and Tom pay as we're going out in talking with potential investigators about our approach and the Nonclinical data, we're seeing a lot of enthusiasm there understanding that the approach that we're taking is is meaningfully different and likely.
To be superior and so we expect to employ a similar strategy in duchenne generate the data show that our approach is best in class and then the patient to patient enrollment follows from there.
Alright sounds great. Thanks My question.
Thank you and our next question comes from Steve Seed House with Raymond James Your line is now open.
Yes, hi, so I wanted to ask the fuse relationship with Avexis and it's gene therapy programs has been rough lately. So I was kind of hoping to clear clear the deck.
Some of the issues that have come up there so first.
Put obviously, they're tied to resume study on hold over concerns of dorsal route gangway on toxicity.
Have you.
Have you seen or assessed DRG talks as yet they reached out at all regarding specific assays or data subsequent to their investigation of axis based on your preclinical work for either excellent or in particular, I guess now the Nch program getting underway.
A question one.
Sure Hey, Steve It's Matt.
Yeah, certainly we're all aware of that news.
But I can.
Reassure everyone that Weve never observed a such.
Events in our preclinical work or certainly our clinical so we have no experience with that specifically.
And we have not heard anything specific from Fdx, a asking questions about our programs that relate to that subject. So all quite on that front and.
Really that's about it I know, there's not much more I'd, rather not speculate on what's exactly going on there just not knowing all the details, but but at least as far as we're concerned we haven't seen it and we haven't heard from India.
Okay I appreciate that that's a good to know and and just regarding preclinical.
Work that so the higher the dose that you're using the pivotal EXL MTM cohort.
Three touched tend to the 14.
How much in your preclinical experiments first of all can you remind what animal models you were in and based on the highest dose you are using preclinically, how much coverage of that.
Or how much coverage of your clinical dose do you have a from the maximally tolerated dose a assessed preclinically.
Sure. So in MTM you know, we did a multiple preclinical studies overtime. There was a mouse work there's of course, the naturally occurring dog model in which we also did dose ranging work and then for a true safety assessment, we did a GLP toxicology and non human primates that went up to eight.
Hi, just under the 14th vector genomes per kilogram, which we still believe maybe actually be the highest dose anyone's gone too.
The data were clean and supportive of the safety. So theres a significant a window there above the chosen dose for MTM future clinical and then of course, most importantly in the clinical trial as you know we've.
Really had a good safety profile than anything we've seen and just a few patients husband easily manage so so we feel very good about safety profile and Worthing said.
Okay, just just last detail on that the follow up.
You think about eight versus three then I think the orders of magnitude were the same if I heard that correct.
Is there any adjustment based on PK modeling or whatever and in different species or is that a one to one comparison. So you have.
Call it two and a half two to three full coverage.
Based on the preclinical work.
Yeah, I mean I guess.
I'll, let someone else feel differently I would say, we think of the primates is the best.
<unk> model and so we sort of think of it as a one to one versus humans.
But you know there's no there was no model is good as humans, when you're talking about a virus like this but all but nonetheless, the best available opportunity for assessing safety and so that's why we included in our programs and.
Certainly an empty on the data were strongly supportive of safety.
Great. Thanks appreciate the questions.
You bet.
Thank you in the next question comes from Roger for solved with William Blair. Your line is now open.
Thanks. It in the question Oh I'm just a question on the pump pay program can you just that's the kind of Directionally to this construct and that's currently 90 submission versus the previous construct.
Is it obviously the safety issues you guys is obviously looked at corrected but from a potency perspective or by distribution perspective, you just kind of talk to to that and then kind of in his prepared remarks, you mentioned the potential superiority of your approach versus somebody other approaches have you.
And taken out the liver directed or kind of optimize for going more towards the muscle expression or G.A. and it's not just thinking about how the gene expression liver from your construct would work.
Sure. Thanks for the question Raj So, let's see I remember just a quick reminder, for folks are the the approach the change the change we made of the product. After we had to step back last year was with the promoter.
But everything else about our approach is unchanged a aviate serotype systemic administration.
Still targeting primarily expression in muscle and so that was really the only change and it was based on a tremendous amount of work and both comment then the mouse model.
And a real thorough understanding of what we observed and I think in the end. It was just a matter of fine tuning to make sure you're getting the right level of expression of the GE a protein and all the right places.
So.
Finally, as once again I mean is good data the preclinical data are very strong I know, we haven't shared that yet, but we look forward to it at world.
And certainly strongly supports the R&D filing and starting clinical trial.
As far as the liver elements you know we're right now we're not speaking about the specific details of the of the promoter, but I can assure you that we are focused primarily on getting expression in muscle.
That is the tissue that we're pumping manifests and that is the most important in this equation. So.
So you can bet that that's the case and overtime here will share more information about it but.
This is a muscle directed expression approach without question.
Great and is that disease specific or is that something that you're taking over into the indeed, well as far as a promote reviews.
Oh, it's a different scientific approach remember in DMD are doing vectrus exon skipping a so as not only described it's it's a different type of promoter situation than than the protein expression that we're dealing directly with them.
But happy to go through that again and I look I go back to that again, if that would be helpful.
You can call player in the worst thanks.
Sure.
Thank you went on next question comes a massive Matthew Lou <unk> with BMO capital markets. Your line is now open.
Hi, great. Thanks for taking my question.
So I wanted to first I wanted to come back to your interactions with FDA and the context of PMT.
Appreciate in the prepared remarks that there was you know a description of every.
Interactions of having general alignment and I heard.
The additional color around around potential concerned stemming from a vaccine.
Just wanted to confirm that that there are or ask if there any spots where there perhaps wasn't alignment yet specifically in the nonclinical RCM see I recognize that into clinical development type things, maybe a little early.
Not would you like.
Yeah sure go ahead.
Yeah, absolutely I think for the question I would say there were no areas of obvious misalignment and the Nonclinical, a and manufacturing areas. We we we had the data in hand from a that was generated with the with the nch construct just to sort of provide a biologic overview of the.
Roche and not served as the basis for outlining what I Nonclinical I'd, enabling package would look like for the first to construct and then subsequent constructs and then on the <unk> on the manufacturing side. Yeah. It was a great discussion because this is one of the the great strengths of our manufacturing operation is not.
Our manufacturing platform that is essentially construct agnostic and so we can leverage not only data that we're generating from P.T. seminar to the first construct in duchenne, but in the data that we've recently generated with her GNP campaign for eight four or five as well.
So so yeah, I think you know that because that biologic mechanism that we are proposing here is unique and because of the experience that we had in our manufacturing process and operation and it was.
A really cordial and sort of enthusiastic interaction with hefty I think were coming in very good stead and coming from a position of strength in proposing this platform approach.
Great. Thanks, and just one more on 87 no too can you just remind us is the ability for you to file your I N D in any way dependent on what happens Patheon CHS Hi, Andy.
Yeah. Thanks for the question. It's a good run to clarify the answer is no. So again, we did well we're in the process of completing a dose finding study in the due to mouse model and a primate toxicology study on our construct those two studies will serve as the basis for I.D. So there's no.
I want to bridge back to the data package on the previous construct.
Perfect. Thanks for the questions.
Thank you.
Thank you and we have time for one further question. Our next question comes with Difei Yang with me, though your line is now open.
Hey, Good afternoon, guys. This is Alex on for the <unk>. Thanks for taking the question and congrats on the continued progress.
I had a quick one on pumping.
So we know you're targeting muscle tissue directly and we we also know that the CNS is unimportant tissue affected in the disease and I'm wondering if you could speak to how youre construct could potentially address CNS involvement in pumping disease.
Yeah sure. Thanks for the question Alex a it's a the point as well taken I would say that was time, we've learned that there's at least a subset of pumping patients for whom CNS involvement is important and so it's something that we do take seriously I would say however that starting out our focus is really.
On ensuring multiple expression, primarily which is critical for all patients.
We are continuing to think about ways that we can ensure the CNS is also properly treated but I think it. It's a there's some complexity there do you need to do the right research to understand exactly what cell types are most affected and find a way to treat them.
With the best approach so.
Not ruling out the possibility that will get expression in the CNS with the existing constructs, but our focus is I'm sure in muscle expression.
And as we learn more from the work, we're doing well be looking at ways to consider expanding the program to ensure we treat the cnf in the patients for whom it's it's an important issue. So hopefully that helps and that's a that's going to us on an interesting conversation going forward.
Great. Thanks very much.
Sure.
Thank you and that's just timing like to turn the call back them out Paterson for any closing remarks.
Great. Thank you everyone for joining us this afternoon and for the option to share our updates we look forward over the remainder of 2019 and of course, I really exciting 2020 to come so.
We look forward to speaking again soon operator that concludes our call today.
Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.
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