Q4 2019 Earnings Call

In summary, we are very pleased with the totality of these efficacy safety and Tolerability results in this LG US trial, demonstrating that same Tesla has the potential to be a new treatment option in the second severe childhood onset epilepsy and with that I would turn the call now back to Steve.

Thank you.

So for taking us through the compelling topline data from study 16 or.

We're excited to be reporting positive results for phase three study demonstrated clinically meaningful efficacy for free tableau, reducing would drop seizes experienced by patients without yes.

In the coming by the screen turns liquidity after year to discuss the next steps towards.

As a regulatory submission for print textbook for the treatment of Geos.

Beyond doubt, yes, we are pleased with the new drug application footprint tougher from treatment duration drum has been accepted group priority review by the FDA areas, where there but do for target action dates are most trying to address this year.

In addition for marketing costs or.

Patient arbitration forefront tougher Intravase syndrome is under review by the European Medicines Agency in Europe, We look forward to running updates on both of these applications later this year.

In closing I would like to thank you Jane for patients families investigators and Scistar from participated in this trial.

I'd also like to express my since sincere appreciation for hardware from dedication portfolio.

Everyone. The subjects and also zero programs over the past few years with through tougher.

We have some very important milestones ahead of us and we'll continue executing our mission to improve the lives of patients.

Families living with rare diseases.

With that let's open up the call for questions. Operator would you please provide instructions.

Thank you we will now be conducting a question and answer session and the interest of time, we ask you. Please limit yourself to one question and one follow up.

I would like to ask a question. Please press star one on your telephone keypad, a confirmation tonal indicate your line is in the.

Do you might start to if you'd like to have your question from the Q for participants you the speaker speaker equipment, maybe necessary to pick up your handset before pressing the star Keith One moment. Please poll for your question.

Our first question comes from the lineup to zero Ahmad with Bank of America. Please proceed with your question.

Hi, good afternoon, thanks, very much for taking my question.

Steve Congratulations on that same data.

I just had maybe one question on the secondary endpoints about medium percent reduction and multi drops seizures.

And I just wanted to get a sense from here.

To the importance of not reaching statistical significance on that drop seizure endpoint that youre looking at thanks.

Yes, thanks dizzying.

Are you.

Asking about the lower dose and on trial in fact, we did not meet structured.

Yeah the basis a good question, yes, we are smaller front, we are lower primary endpoints. It was a key secondary endpoint a recall. This these are the same two doses that are reevaluating altra base syndrome on history of including not focus was to establish a minimally effective dose. Although we're seeing survey we did do.

About pricing be quite quite clients being significant and LG asset was no but it was there is an exploratory dose. The primary endpoint was around the high dose of 0.7 milligrams per kilogram per day.

And just what that impact in any way what you think.

Doctors, we view as a clinical meaningfulness.

So for dataset overall.

We now have you noted tool.

Because they have put that these type it takes more clearly informed the label in terms of pro doctors will describe this drug for patients.

We don't think is going to have any other impacts.

Okay. Thank you.

Thank you.

Thank you. Your next question comes from the line of Paul Matteis with Stifel. Please proceed with your question.

Good day, taking my questions I Hope you don't mind, if I have a couple.

On.

On the efficacy side I, just wanted to kind of clarify.

You hadn't.

Theory surrounding the inevitable Krakow comparison as it relates to your screen the epic directs LTPS study it looks like the absolute.

The reduction was lower but also the placebo effect is our is our warrantless Exterran told I was wondering varies on that are looking at the baseline curricular patients are greater than Pops up and then.

Second Ondeck RCR parametric analysis, where the gate abnormally distributed is the right way to think about the data to parametric analysis or the or the primary analysis and then I just have one quick follow thank you.

Yes, let me take their problem answered. This is not part of metric and Gail maybe you can take the second question from Paul.

But clearly the primary analysis was actually known power metric.

Using announcement covariance.

So the first results that scale provides you are the primary.

Is the results from the primary endpoint. The parametric analysis was allowed also within the.

Within the saw on numbers there to support the filings for the.

But there was not the.

First method was alone parametric.

With respect to date to allow us to running parametric analysis yesterday.

Sure and then I'll add to that response that.

Not parametric was selected because the number of seizures patients how that baseline was was a wide range. It was highly variable and so non parametric is often selected for that reason as the prospectively designed primary as we did with regard to interpreting our data and GW is data.

Yes, our placebo response rate was low and our.

Our active response rate, which was statistically improved was three times the placebo response rate and if I remember correctly.

You had a much higher placebo response rate and I think they're active rate was two times higher so they are different studies run at different times.

And it is always difficult to make direct comparisons in that situation.

Okay Fair enough and then one question on safety can you just clarify.

What drove the difference in SC rates between the high dose low dose and placebo and if there's any pattern there or or anything.

Noteworthy any color I appreciate it thank you.

Yes, good Gail to address that as well so.

Good point and actually most of the essay ease were due to hospitalizations related to concomitant diseases or infections that were unrelated to epilepsy and considered unrelated to this.

The study drug so we think it.

Just to be phenomenal.

Thats a numbers came out to appear to be dose related.

Okay. Thank you again, Steve appreciate it.

Thank you Carol.

Thank you. Our next question comes from the line of Danielle Burrell with Piper Jaffray. Please proceed with your question.

Question.

Hey, good afternoon, everyone. This is an arrive on for Danielle I just a couple from me off what you would you know what the median reductions in the 50% reduction.

Your frequency rates were for all Caesars type.

The we dropped off.

This is subject to further analysis, where you don't have the update your nose up yet.

Randy will be looking at the entire data sets and moving forward publishing dots in due course.

Hi fee and with the idea that you currently have how are you now thinking about pricing same capital.

There are many factors that are going into the pricing of France outflow.

Work is actively on growing right now.

Of course, we hope that will be in a position to set a price or fins outlooks for the treatment of drove a syndrome coming up in early April so.

That's what I can say at this moment and with respect to.

Our strategy around pricing.

Got it thank you.

Thank you. Our next question comes from the line of Marc Goodman with SBB Leerink. Please proceed with your question.

Yes I.

Given the data that we saw in the truth a.

Studies that was just so.

Robust I guess the question is you know should we and the investment community have been thinking that the LG EPS was going to be as robust as I think there seems to be have been.

An expectation that it was going to be.

I don't if what's going to be as good as driven certainly very good.

And certainly much better than where the epidiolex kind of data was and so I guess I was just wondering if you had any explanations for why it should be different intra day, and ltacs and whether those expectations that we're out in the marketplace were just a little bit too aggressive or just how you're thinking about that thanks.

Let me now, though with the Guy who I think she's addressed a little bit of that I'm going to it responds to full.

Saying first and foremost that comparing across trials run at different times and in this case in different patient populations is.

Well, it's generally not not an advice.

Debate is.

Acknowledged it's a very Mr. Genetically based disease, 90% of the patients have mutation.

Specific sodium channel, where as LG us is very heterogeneous and is very hard to treat and that has been well documented so.

Against that background when there are many many many just many I was at six.

Approved treatments for Ldcs and still we enrolled quite quickly 263 patient is quite a lot of unmet medical need and people who are highly resistant to treatment. So it's always difficult to characterize.

When you're treating a resistant population if.

If that is a factor in the delta.

That you see drug over placebo, but it's very important to recognize that the improvement that we saw 3.4 times when they active versus placebo in the domain study. It was about three times drug versus placebo, So and GW I think I said in LG EPS was two times drug over placebo. So there's many lenses.

Through which to look at this end.

We are very very grateful that is clearly positive trial. The 0.7 dose provides benefits to patients with LG us and we look forward to the opportunity to talk to the FDA and unit.

Thanks and.

And just to.

To be clear you're planning on filing for Lcs and when you take into account.

And LG syndication as you're thinking about pricing for survey in a few months right.

But as I said Mark earlier, there are many factors going to going into a our work around pricing et cetera.

Enterprise and though we won't be focusing hopefully doing that's a once we got approval for a friend tougher for the treatment of season, so its which are very syndrome.

Okay. Thanks.

Thank you. Our next question comes from the line of Jason Butler with JMP Securities. Please proceed with your question.

Hi, Thanks for taking my questions and sorry, if this is.

Another follow up on Paul's question, but can you just again going back to the placebo rate speak to whether this and the baseline medium season right were in line with your expectations. When you designed the study and then just second question have you looked at any weight based store.

Space analyses and do you have any thoughts on how useful these kind of analyses could be in this patient population. Thanks.

Jason we haven't done any analysis.

Rate base. These our topline data across where you will be looking at many aspects of this data sets.

We have time I will say that the randomization more stratified by weights and so we think theres. Some shows on the demographics, we had a fairly consistent ways across will oh across all our groups. So looking at any correlation between wait until we saw an efficacy where you will.

Overseas do in the future.

Could you remind me of the first thought your question.

Yes, just one it's a placebo rate consistent with your expectations. When you design a study a and b the baseline median.

Seizure frequency.

Yeah, we.

It was.

It was powered spreadsheets or look for a 30 point difference.

Randy.

I was able to.

Haven't study, which is very positive with a P value. Your point is easier ones, who though you always go into these studies not knowing precisely.

Receivable on our two responses will be you just estimated.

But I think the fact that we have a positive study, which met its primary endpoint with high significant says that we're very happy with the outcome.

Great helpful. Thanks for taking questions.

Thank you.

Thank you. Our next question comes from the line of God.

Since then I have with Guggenheim Partners. Please proceed with your question.

Hey, guys. Thank you for taking my question just a couple from me can you probably remind us if one trial is sufficient for approval in algae asked do you sort of have any prior agreement or guidelines from the FDA. If only one trial is.

Acquired and I have a follow up.

Yes, yes. Your we've we've already had that discussion with the FDA. So.

Away and this will work out is.

If we have approval.

For the shouldn't sampler, Andy I think in Dravet syndrome, where we all see conducted two independent well.

So trials event, a single trial, and then Skus there will be appropriate for us to submit supplemental India. It's about no approved at the right. So that is our regulators restructuring.

Great and then what are you able to look at.

How many patients hit the man daily Max dose you know any sort of.

The French as you saw inpatient that did not hit that hit the macros versus who did not.

Yes, I think that's probably goes back to the prior question about the impact on weights home efficacy announce an analysis that we will do at some point in the future or we have conducted thought as of yet, but I think are.

Impressions is unlikely to be a major concern contribution here with respect to wait on on drugs and on efficacy.

Got it and then just final question can you maybe remind us the significance of the CVI endpoint. Tony you evaluate did to end 0.1 was proportion of patients that have improved versus very improve just on there were some day.

French isn't the results you just remind us the significance of these endpoints.

Yes, a great question Mikael.

Thanks, Steve.

Can you just see T.I. is a holistic measure the physician is rating not only seizure control, but also tolerability and other endpoints that may or may not be measures such as.

Cognition, such as better speech, better eye contact center physicals motor ability and it all gets rolled up into one number.

As I said the anchors are one is very much worsened for is no change in seven is very much improved.

Next is much improved and spot comes on backwards one is very much in.

Improved two is much improved and threes minimally improved so there's two cups, you can love everybody, who had a one two or three those were all people who are directionally improved but some of them. We're only minimally improved or you can lump only numbers one into those.

We're all people with significant improvement and in the data that we showed there was a a dramatic and significant difference when you looked at those on the 0.7 dose versus placebo if they were.

Much are very much improved versus the placebo group that was 14.3 nurses the lowering.

With a highly statistically significant change.

If you add in those will only minimally improved the proportion goes much higher.

In both the active group as well as the placebo group. So thats the significance of the two different cuts of the data is there anything fintech FFO was certainly having a dramatic effect.

Checked on being much improved are very much improved.

Thank you very much.

Thank you.

Thank you. Our next question comes from the line of defy Yang with Mizuho Securities. Please proceed with your question.

Hi, good afternoon, and thanks for taking my question.

I'm just a couple here what would you be able to tell or roughly what percent of to patients well on two class C D and and also remind those small off those background.

Treatment is pit Daleks being one of the option.

I'll hand over to go as well.

Thanks, I just think we don't yet have the breakdown of of how many back on Eightys, we'll have that I'm going to future communication and be dialects was not approved during the majority of the time. This study was running and so I believe none of the patients.

We're on every dylex during the conduct of this trial.

Before I will say is so we do not allow CVD into the trial.

Okay, but.

We had a history of about 25% for patients who have experience of CVD, but discontinued product coming through our trial and that's.

All forms of CPD, so cultures that be deluxe.

Yes, Thank you for taking my questions. Thanks.

Thank you. Our next question comes from the line of Tim Lugo with William Blair. Please proceed with your question.

Thanks for taking my questions well did any patients achieve drop seizure freedom and.

Either arm and the maintenance period.

And also can you discuss a few unfortunately case, a food up and how confident are you there was unrelated to study drug.

So I'll take the.

The second the second question first he investigator is the.

It's the one who has had the relationship with the patient with patients families.

Nod and receiving the medical records related to the case it was the medical director the investigators opinion and concurrence by our medical monitor and that's going to death was very unfortunate but no.

Since you believe it was related to study.

Treatment.

Okay. The other question with respect we haven't looked about analysis yet.

Tim We got will be something that we will reports on Italy today.

Okay dropped the drop seizure freedom.

Correct.

Okay. Thank you for the question.

Thank you. Our next question comes from the line of third Salinger with Needham and company. Please proceed with your question.

Hi, good afternoon, and thanks for taking my question. The first one I'm not sure. If you can answer this evening with.

With the dataset, but can you.

Tell us how quickly you.

You saw statistically significant separation between no treatment and placebo within the treatment period.

And the debt difference or increase overtime or Wayne overtime.

So we we don't have.

Thanks for right now in terms of has been able to report two dogs are we think it's likely that the drug because we're quite quickly. We certainly saw about underway, but we're looking forward to conducted on analysis later on.

Okay.

And I'm not sure if you've covered this but how many of your.

Patients from the trial went on to the open label extension study.

93% approximately all the patients in randomized control trial wins into the open label extension.

Got it.

Okay. Thank you.

Thank you. Thank you.

Thank you once again as a reminder, if he would like to ask a question. Please press star one on your telephone keypad for participants using speaker equipment may be necessary to pick up your handset before pressing the star Keys. Our next question comes from the line of Michael Higgins with Ladenburg Thalmann. Please proceed with your question.

Except for thanks, guys for taking my questions just one quick one.

You mentioned that CBD was not allowed any point in the try on the trial Lexus proved around the time, maybe if study start but for the patients weren't allowed to go onto that did you test for CBD anywhere along in the.

That's what gives you confidence that the patients or using CPB, where is there any additional instructions given by the T.I.s to the family.

Yes, just to correct one things Michael.

Epidiolex was not approved at the time to this study was ongoing.

This study enrolled quickly.

Quickly in the United States first on the United States enrollment was essentially done by the time its products have been approved and then the strode switch to Europe.

Got it was not approved so.

It really wasn't available as a medication during that time, where we were running the study.

With respect to monitoring for CBD use yes are we sit down right through the study in the same way to date with rebate, though Charleston for right.

Were there any use of CBD in those blood tests.

Not that nothing I recall.

Thank you.

Thank you.

Thank you we have reached the end of our question and answer session I'd like to turn the call back over to Dr. far for any closing remarks.

Well. Thank you operator on my fuel for your interest in progress. This agenda. This team is really pleased with oppose the results from a study 60.

No one.

We believe in tough warehouse potential become an important new treatment option for patients with LG us and we certainly look forward Giovanni with further updates through twentytwenty you'd be armed with us and thanks for joining us today enjoy the rest of your day. Thank you.

Thank you. This concludes today's teleconference. You may disconnect your lines at this time.

Thank you for your participation and have a wonderful day.

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