Half Year 2021 Inventiva SA Earnings Call
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Good day, and thank you for standing by welcome to invent Chivas first half financial results presentation at.
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That ought to have the conference that puts your speaker today, Fredrik Cran, Chairman CEO and cofounder. Please go ahead.
Thank you and welcome and good morning, everybody good afternoon, and welcome to the first half the southern 'twenty one financial results.
So as usual I'd be making and the team will be making forward looking statements. So please refer to the regulatory filings that are available when our sites or at the SEC.
Iridex.
Today I'll be of course the sharing.
Presentation, we scare people, a guy who are cyclical Thunder and Michael Kaufman, our CMO, who will be presenting at the latest on the <unk> I will be speaking in introducing some very exciting news concerning our partnership with Abbvie and the recent progress Altice Europe N G.
Joel will be presenting of the financials and our financial situation.
The first half with this year.
So without losing too much time, let's look at what are the highlights of this very busy for stuff.
Quick turn.
What what was our ambition at the beginning of the year, we won't be at the low our goal was to have the pipeline by the end of the year we've.
Compile Lenny if you run or in phase III and figural guidance in phase two b and they seek we are in a very well positioned to achieve both goals. So let if you brought in are you seeing that recently, we have announced that we have started screening.
In the U S.
With our powerful global park, the radical theory and that we have qualified more than 330 sites in 25 countries. So we're really pleased by.
By the launch of these exciting phase III and Michael will provide more background on the design and now to start the study is rolling out.
The good news also comes from.
Here again, the BD Wednesday, seven so you followed during the Q1 as the Q1 result that they communicated to have achieved clinical.
Clinical proof of concept during the phase one b in patients with psoriasis and we were extremely pleased and happy to see that in.
On September 14th when clinical trial Dot Gulf that'd be posted the design of the upcoming phase two B, we said Europe in patient with Horizon very important study 200 patient 45 sites.
And especially they are concerned that this study will be up and running.
In November which should trigger a milestone payment for us.
Of course, we are already looking forward to the results of this important study which are scheduled for March 23.
Concerning on the powerful we're continuing to actively.
Evaluation of the strategy of the best way, who best options to continue moving this program forward will not be able to update the market in 2021, as we plan to do that in 2020.
Concerning.
The other important events of course yard, where we have been able to launch a phase III also because we've been able to reinforce our team on both sides of the Atlantic So.
Michael is now.
Leading the team.
The U S. All devoted to the phase III and also in France, we have reinforced our key position. Both in terms of Superfund showed medical's cleanup and we're really geared and prepared for this phase III.
Over the summer was put in place an ATM.
The expected as many.
I think listed in NASDAQ due and this gives us additional flexibility in order to reinforce.
Our cash position with the possibility to wear decided VTS 200 meters.
And then finally, we have reinforced our board with the arrival of Mckinsey lumen, which who we provide at least providing valuable.
Regular to reach 30 is given.
Our position currently at.
Alexander after that.
So therefore for the short intro and now.
He is a floor for Pierre.
A brief update on lending on lightly fever.
Yeah.
Thank you for it.
Hello, everyone. So.
Then if you been door is a <unk> agonist, which is currently in clinical development phase III for the indication treatment of Nash and improvement in liver fibrosis.
It has an unprecedented structure and pharmacological profile.
Upon people agonist with moderate.
Well balanced activity across the three isoforms.
The title is in dire sort of sideways.
This program a servicing fee.
The pain breakthrough therapy designation as.
That's what our fast track designation from FDA.
And FDA has also a concern.
Confirmed recently that the non clinical toxicology package.
Is complete and acceptable for an NDA filing can.
Can we go to the next slide please.
Following the successful outcome of the.
19 phase two b trial with lending should be nor in Nash, yes.
Yes, it started our phase III in patients with Nash and fibrosis score of two or three and Michael will present the detailed.
And the key milestones of this study.
To complete.
The clinical development plan.
In Nash.
And besides the study in collaboration with Pfizer Choosy.
Waiting the effect of lending should be nor on insulin resistance in diabetic patients with Nash with deep.
We are also progressing on the preparation of additional clinical studies evaluating the potential of <unk> in Nash compensated cirrhosis in this.
On the back of positive preclinical findings that we have recently published.
And we also are progressing in the preparation of studying.
To evaluate the potential of lendingtree, but nor to be used in combination with other therapies.
To further strengthen its value proposition.
So the natives two trial next slide sorry for that.
Yeah.
Yeah.
So do they these two trials indicated that after 24 weeks of treatment with 12 milligram dose had a significant effect.
On improvement of fibrosis by at least one stage no worsening of Nash.
And both doses 1200, and 800 milligram had significant effects on resolution of Nash and no worsening of fibrosis.
As well as on the composite endpoint of resolution of Nash.
And improvement inside resources, where a responder is defined as a patient showing both Nash resolution and improvement in fibrosis.
Additional analyses were performed and communicated earlier this year easily.
Decentralize this indicated that in patients with Nash, if two or three fibrosis.
Sure.
So significant efficacy in the composite endpoint.
In this group were observed more than three and more than four times more responders in the low and high dose group respectively.
So observed in this subgroup of patients with this two industry leisure fibrosis markers of lipid metabolism insulin resistance liver injury and inflammation and fibrosis also improved with entrepreneur treatment at week 24 compared to placebo.
Go to the next slide please.
So based on the latest two data.
And should the neuro showed key differentiating benefits.
Compared to the current competition.
And particularly on insulin resistance.
Fibrosis, which are as you know two important but all the chicken features of Nash.
And the latter by Bruce is being as you know as well the primary determinant.
Clinical disease progression.
Patients with Nash.
Next slide please.
As can be seen on this slide and compare to the current competition.
Then it should be nor is the only drug having achieved statistical significance on the key regulatory endpoints.
Industrial solution without worsening of fibrosis.
And fibrosis improvement without worsening of Nash.
This with more than 40% responders.
For both a regulatory endpoint.
Well go to the next slide please.
Yeah.
So we did that is to results we conducted interviews of pathologies.
Ross U S U K, Germany and France.
And these interviews indicated that the physicians value lunch was the most efficacy.
Different points as well.
Once a day over mode of administration.
Next slide please.
Yeah.
The physicians will supersede weight gain is acceptable considering the benefit of multiple decision points.
It's existed that weight gain could be offset with either proper patient counseling around weight loss.
Or by combination therapy with for example, Cherokee one receptor agonist.
Or is she until two inhibitors.
With that I will now leave the floor to my co.
I will say a few words on that history.
Thank you P S and move to slide 16.
Have started Ah recently, the pivotal phase III study, it's conducted in patients who have Nash of course in a stage of fibrosis F. Two F. Three that's based on histology and.
To find patients who actually most in need of treatment.
This study consists of two parts and D.
The inclusion criteria yesterday.
<unk> exclusion criteria or.
It's very similar to the ones in the native phase two b trial in order to.
Guarantee consistency the two parts.
Define actually the objective to Oh.
Okay and accelerated approval after they get in the house 72 weeks of treatment.
Part one based on surrogate endpoint, which is histology.
And then in about.
About two which is in a strong but of course, it's up to seven years, which would look at outcome and outcome is the foundation for full approval following actually cool it.
A randomized double blind placebo controlled smoky central of course.
Evaluating the long term efficacy and safety.
No not in adult patients with Nash and fibrosis.
We evaluate two doses 810.1200 milligram in the phase III study that will give us information about the efficacy of both doses of.
When treatment is stronger than in the phase two study, so a year and a half will be.
Two weeks ago BD evacuation of histology.
Yeah.
The principal investigators, we have professed set of San Fran and.
And to Merck and Professor Arun Sanyal in Richmond, Virginia, and it'll be too.
Our principal investigators.
Inclusion criteria or adult patients of course, they have to have Nash and in order to make sure that patients.
Active disease, they used to so called skip doses activity fibrosis score with an activity of more than three or more histologically and fibrils afterwards and definitely for the inclusion criteria.
And organization is 111, and we do have a stratification. According to type two diabetes and.
The staging of Cypress in order to guarantee that in all arms that doesn't equal amount of diabetes.
Diabetes and fibrosis and in about two and I'll also have.
Define what's the minimum amount of patients who have F III, which will enable us to detect progression of disease and the effect of debt off of our.
Children off.
At least 30% will be patients in the United States.
Powering as stringent based on a 90% power that's what's the basis for the sample size calculation and we have.
Established expert pathologist, who will read the biopsies.
It's for screening for enrollment for our eligibility.
<unk> ability and also then for the evaluation of the efficacy.
So in part one of the primary efficacy endpoint is a histology as I mentioned to roughly 900 patients will be enrolled in that study and we have set the bar. According to the data from our native so the primary efficacy endpoint as a composite endpoint.
Ah patients, having both resolution of Nash and improvement of fibrosis.
According to the C N criteria and that's about the treatment and Macy's and I think that this and.
Very good sign of efficacy, we have key secondary endpoints, which are or.
Each of those launch of Nash resolution and no worsening of fibrosis is one and fibrosis improvement and Nashville are sitting.
Here's another one and then there are several other secondary endpoints, which.
The chart also based on the efficacy shown at Natus.
Selection of dose most important ones from the clinical perspective or.
Listed here of course, we look at it.
Beneficial effect of lot of children on metabolism.
Control have glycemia.
Throughout the study at 36.
In Ah patients with type two diabetes as you know that's significant percentage of patients with Nash have type two diabetes.
We look at the effect of Lama Cyprinoid on H B C.
Which is also not in Maine.
And made sure.
Both basic vision and in Nash progression.
We look at the composite endpoints of diabetic patients, having both Nash resolution and fibrosis improvement. That's also again base.
Based on data we have from from native.
We don't really look at renal function in patients with Nash of course are.
Also have.
Renal.
Kidney so it also involved in the in this metabolic disease, so that could be in.
Got it.
Relevance a secondary endpoint.
And the reduction of the cardiovascular risk.
And other than a positive term improvement of cardio metabolic health, we would measure quality of life you have another question is.
And together these data based on the primary efficacy endpoint.
According to the guidance of the FDA for accelerated approval.
United States and conditional approval by the EMA.
European Union so that's the.
It is important about one equally important is in part two which is the longer duration to look at the outcomes.
The foundation of our.
Full approval and outcomes to define this progression to cirrhosis or liver related outcomes.
Progression to cirrhosis, which probably is what I can see them. Most frequently in these patients who have advanced fibrosis.
Screening methods in place to detect noninvasively when it's a.
Probably be the right time to do a biopsy to 212.
To evaluate progression to cirrhosis and all the components of this endpoint and so on all cause mortality.
Patty decompensation events and citizens hasn't Curtis or events like our site is a portal hypertension encephalopathy.
Mel score above 15 or higher meld scores.
Score, including Bilirubin and.
Which reflects a liver function and liver transplant, which can also of course specific these patients develop an ex U C. Before they have sort of done before to compensate so the outcome improvement as the basis for full approval in the United States and EMEA.
Next slide.
This primary endpoint, where we look at both Reza.
Resolution of Nash improvement of fibrosis.
Well suddenly a clearly differentiated from other compounds for children and advance development.
It's.
It actually reflects the efficacy of longer febrile nor as.
Keep an agonist.
Acting beneficially.
All aspects.
Thanks, Bob.
Defense, that's constitute Nash stocking metabolism lipid metabolism close metabolism insulin resistant inflammation fibrosis.
People are signaling hasn't beneficial effect of all of that which is fine.
We see this as a strong effect on resolution of Nash and fibrosis, So thats a competitive advantage.
And that will also be the foundation of the.
The label.
And the bottom of the slides comparison with two other advance some funds so because the holiday assets.
And until we better receptor agonist is meant to run which is.
Also in phase III.
Now, let's see Bernard is the only compound that resolution of Nash.
And improvement of fibrosis.
And we have also as you've seen.
The promising data in patients with diabetes.
Next slide.
I mentioned at the beginning that the phase III study has started.
Oh, we have to.
We do one pivotal study that's also because.
A lot of children or has received breakthrough therapy designation from the FDA.
That is around and many.
Geographic areas as you can see so the U S North America, South America, Mexico.
Large most European countries, South Africa, and Australia. So the overall 25 countries and we have more than.
300 <unk>.
350 sites, who are participating in the b.
Have a huge interest from side some investigators in almost all of them based on the.
Positive results that we published earlier.
With regard to the timelines at the high level. So the key milestones to study has started as I mentioned.
That was the first sites activated since those patients screened.
In the second half of 'twenty 'twenty, two we plan to have them.
Yeah.
To have the last patient first visit.
And talked one of the studies.
900 patients who would.
Provided data for accelerated approval and then first half of 2024.
<unk> for the last visit is anticipated, which 10 will provide to the results of parts one of the headlines of zones. Yeah in the second half of 'twenty 'twenty, four and Thats been the.
Foundation for the.
N D a N D.
The rest of Florida.
Chinese approval.
And my last flight a save the date for R&D here somebody which happens in every year at the end of day.
He is in November of this year.
Unfortunately.
Virtualized if you wish after they initially.
To have a hybrid meeting, but it's still a very good opportunity to Europe.
News and.
About Nash and in our investigational compounds and we also plan to have on a dedicated meeting two hour.
Leading.
Herpetologist and Gastroenterologists are from.
From around the world. So it came out of the meeting.
But that's.
Okay.
The floor back to P. S.
Thank you, Michael actually and the colder.
Present to a brief overview of Bobby and I was trying to convince you to convey the excitement that we have a.
Program and with the collaboration with Abbvie.
So we are first of all we're scientifically I think this has always been the case for Oregon made a fantastic target because its targets.
17 expression modulates th 17 differentiation in 17.
As you know is a target that is.
Can you indicate validated by many biologics that they've built.
First of all in.
Many autoimmune disease and have reached you'll see it in the next slide substantial sales.
The segment also continue when you look at where these targets could apply do you know that we're developing.
Mother to see Europe, psoriasis, but some of the preclinical work we have.
<unk> done with our park, the raspberry and that has been published.
758, either order compounded neuro again, Steve.
Making those action and Youll see a result.
Several of the relevant model of cope for Ics, but also.
Try it and therefore, there is a possibility to develop.
So in Europe again.
The multitude of indication.
We know that Abbvie is the experience.
The team there.
And then also the puts.
The ability to develop 10 year regarding several indications.
So if he sees why scientifically it's exciting it's also exciting of course financially it's exciting because.
From a financial point of view, the collaboration with fit up with Abbvie and type of symbol kiva to receive milestones and royalties in the deal is backloaded. So the royalties that we've received are not transformative the last one with towards the initiation of the phase will be $8.0 million.
Neuro. So you see that it's nice to have but doesn't change our financial situation, but instead the royalties.
Does that mean.
Single digit timken reached double digit or certainly very attractive, especially when you look at the sales potential that has been reached.
Some of these IL 17, and you know once again I remember when we started that program with our colleague at Abbvie. The team used to call. This program with the ambition of the program you mirror in the period with a better safety.
<unk> reached that I am convinced that the inventory will.
We'll be able to receive double digit royalties on the sale of Europe.
But at this time. It also comes from the progress made by by Abbvie and also by you know the quotation. The quotes are what makes it a real estate during the Q1 result of that.
Business here, where not only they confirm that.
The year ago, Ed achieve.
Achieved clinical proof of concept in patients with psoriasis by measuring the Patty score.
But <unk>.
Even more by the fact that they believe that with a year ago they'd be looking.
You can see it in efficacy.
You mirror or greater.
With a good safety.
And this is exactly what the ambition.
The program.
And then the last excitement called problem, a very recent news published by.
By Abbvie on clinical trials Gov. Please.
If you want more detail do not hesitate to look at the distributor, which we summarized here.
Important trial sponsored by Abbvie.
Which he start it's going to start very soon in November.
<unk> is entitled to a milestone with the first patient will be included in the study.
The study aims to recruit 200 patients, which will be treated for a 16 week treatment period. The proceeds of at least 45 sites in the U S. So you see an ambitious program, which is planned to finished November 'twenty. Three it's also one of the advantage of horizon.
So the relatively.
Sure the duration of the strike.
On the right of the slide you as the values the primary and secondary endpoints. So for those who follow this space I think it will be.
Happy to see that the typical measures.
Included in this study are included especially of course, the past score.
And then lastly, also the sites will come from the overview about the competition of course is the wrong Guy made a very exciting target many.
It takes or large pharma has tried to develop.
Our neuro raw guidance, but when you look.
Today is the competition you see that Abbvie, we said Europe is very well positioned to be a first in class and best in class as many we have attempted to develop Aurora gamma has failed.
I have failed either because they were not able to develop.
Overall.
Formulation. This is a case of GSK pfizer or because they had.
Safety issue like like Garlock.
Overall, we really are pleased with our progress.
Really looking forward now to the beginning of this.
Phase two B, we said Europe.
So these four for the brief overview about this great programming.
Gives us score to Joel will provide us with an update on the financial situation.
Thank you Fred Eric Good morning, Good afternoon, everyone. So well, we're still are relying on a solid ah shall debate rather unchanged.
The the NASDAQ IPO in July.
There are no financing activity as you know for this semester and in terms of market value.
We are if we may see backing the green after the Easter heat during.
During the summer when we announced it at.
All the all back to the value before the ATM.
Quite good shape.
However, we are still believe believing that.
Considering the potential of our programs.
Probably under value the peers.
And we hope we will.
Prove that in the coming weeks and months.
We can review now.
Next slide the key financial.
In terms of the festival quite straightforward and more importantly, he.
He is in line.
With our budget trend and our operational roadmap in terms of the P&L.
No revenues recorded during the semester, but.
As we said we hope.
This language can move by the end of this year with the enrollment of the first patient with as planned.
According to design a study.
November 21.
The key information obviously this strong increase.
And the R&D.
<unk> expenses.
The $19 million compared to $18.0 million last year obviously.
The it's reflect the acceleration if what have you seen and which are dedicated to the development of 93% are under preparation give lunch.
The 93 year phase.
Going along with the reimbursement of the development.
Development E Commerce EMA.
And the accretion of our U S aggregates, where 100% of our staff there.
And then if you want to.
Also.
An important increase in G&A again, Oh, yes.
R&D expenses represented 75% of our operations.
Operating expense and G&A increased as expected.
This is exclusively due to the fact.
That's since last July.
On the NASDAQ rules.
Compliance costs.
Insurance legal or accounting.
Fully in line with budget.
Because here, we are comparing the semester with a semester last year.
On Euronext and we are also implementing to match the U S regulation, we're implementing on sort of the southern nuclear and refined sugar.
Be ready in case, we would we would switch.
U S GAAP.
In terms of cash position, we are let's say a reasonable guess.
Position at $99.0 million compared to $105 set lot.
Kevin last year.
Driven debated consumed confirmation of the of cash flow neutrality at $27.0 million compared to seven two.
Directly related to the trend of the expensive.
In RMB.
Dynamics of the sunlight was two five per month.
During the last semester.
Now.
<unk> estimates that $10.0 million per month or per month, and we are adding.
On average 6 million by the end of the year, which is in line again with.
The.
The development of the study.
I will be happy to answer your question more detailed question if needed during the Q&A session. Thank you.
This is also if we look at the near term catalysts of course for this scene very busy first six months with menu our objective it is bill.
Metal on the various programs.
Well certainly Glenn.
We will of course provide a regular update concerning the development of the pivotal phase III and also we're looking forward to the results of the study that is going ongoing currently.
In the U S had professor <unk> numerous to Florida.
The powerful momentum will provide you an update 2022 and of course with zero again, you should expect to a year.
From us once we once the trial is launched and will receive it.
Milestone for the initiation.
The phase III.
So these are the new then update we wanted to share with you and I suggest we move to the Q&A session.
Thank you if you would like to ask a question over the phone. Please press star one on your keypad and wait for your name to be announced and accounts to your question. That's the hash key.
On one of questions.
The first question is from the line of Lucy Codrington from Jefferies. Please go ahead.
Hi, there thanks for taking my questions just to see.
Lastly on the anticipated Abbvie milestone should we think about that as being in a similar ballpark to the Mustang you the seats on the phase one and to us as patient day, saying Oh given JCB.
Is that likely to be a bit more.
And secondly, do you have any insights into their recruitment status Pakihi study and accordingly, do you see any risk to the April 2020 completion.
Suggested on the clinical trials entry at the moment.
And then with safety.
Safety for treatment.
So suraj this amendment and focus given the JAK class.
What are the key safety concerns when it comes to talk single Gamma.
And it is safety the key risk to the phase TB, but.
Any concern regarding.
Efficacy.
And with that I'll jump back in thank you.
Thank you Lucy.
I think the question about the milestone.
The situation of the Qt study and May be here, if you can comment about the Tox and safety.
About the JAK class and any potential read through.
We will again.
[laughter] quite a quite a good question because it's actually for us when we look at the difficulties of the JAK class, we see it as a great opportunity because.
Not only obvious now too.
To deal with the replacement of the Humira, but also.
Medicaid accounts less on the JAK class on its own JAK two to achieve that and therefore.
Europe is might become even more important to them.
But we see what's happened to.
The development of a year ago.
Back to the milestone that is linked to the phase two b. So once again. These are the milestones are not transformative what is really transformative in the deal are the royalties which are.
You know that can reach double digit which.
We are a partnership that was established preclinical it's quite quite than expected and quite high.
And therefore in terms of milestone.
They of course increase over.
The most of the program will advance, but they remain.
Relatively relatively small in the meeting.
In terms of the Qt study about the recruitment. So this is an investigator led.
Driven by Professor <unk>, so he's in charge of the.
Updating the clinical trials the Gulf.
Each one is the one in charge of taking it to the res April we can only rely rely on that I think what is important to point out about this study is that.
The study that is of course.
<unk>.
To learn more about about <unk>, especially in the population.
Type two diabetes.
But once again, it's a different not the Nash population.
It's a study that is supportive, but there's no impact on how we run and carry out our our phase III.
Maybe on the on the potential talks or safety off road gamma and insights you want to share.
Yeah sure so just as we've been.
<unk> mentioned you see the public sector is the number.
Safety issues that have been.
Concerned like serious health related events cancer blood clots.
I would say that.
The checks are very very of course, it would be kwiecinski expressed actually so did you are reacting on multiple type of sales. This is different football gamma which is much more specific.
Specific to the distributor.
So and co.
From the best Spirit experience we had.
So on that piece the preclinical models, we haven't seen them.
Uh huh.
Cvs side effects at all.
So I think clearly the safety profile of Florida, but I wouldn't be too different from some from the JAK class.
I think there was one.
And Oh here comes down to this speed and.
Terminated due to safety reason. This is you have got a good product.
I assume.
The compound was free and displaying specific.
Net targets related stuff.
Yeah.
Increase of Lytham partners.
In the quarter of the patients quite cut it.
So in a nutshell, that's in the hog unless it would be.
Very very different than what we are sort of protect so far.
That's great. Thank you.
Thank you. The next question is from the line of Linda <unk> from KBC Securities. Please go ahead.
Hi, everyone. Thanks for taking my questions three from my side.
Perhaps the first one from Michael I was wondering.
Just to get some sense of potential patient recruitment could you, perhaps remind us how many patients.
Do you roughly expect that need to be screened for inclusion of the total first 900 patients of part one.
Our next question is on brother clinical development of money. So.
<unk> and <unk> combination settings have been alluded to since the phase <unk> results I was wondering if there's any visibility on when these could be initiated or what events could trigger their initiation also in terms of scope should we think about smaller proof of concept trials mid stage trials are immediately multiple trials and then the last question.
I'm just curious about the drivers behind the delay of the outcome of Oh, the parcels strategic review so curious to Europe.
Your opinions on that thank you.
Yeah. Thank you I.
So the first two questions.
So maybe you can get.
Fredrik can answer so Nash studies have has had relatively high screen failure rates of course for them for a reason.
Instead or they have to do with the disease and the need to have a histological.
Diagnosis and staging in the trading of the disease.
Has it been actually around 70%.
That's actually has been relatively good if you compare with other studies. We have just started those studies. So we do everything we kind of close to.
Efficient.
Uh huh.
A number of.
Let's say our approach is to try to.
It used to screen failure rate as much as possible.
Example, by implementing our imaging fibro scan before patients are considered for biopsy.
That's it by that approach maybe hold that we can keep the screen failure rates.
No as long as possible within within the.
The setting of Nash of course, so it's too early to.
Of course, with our screen failure rate will be but.
We are aware of these challenges.
Together with that.
Our partner.
I can and our investigators.
We do what we can to reduce debt.
The.
The.
A question about cirrhosis is a good one.
Clearly.
Patients with Nash, who have progressed to cirrhosis.
At present.
Unmet medical need to them because they are at risk for them.
Complications of cirrhosis, and ultimately need for transplantation and there has been not really.
Much.
Success in that field, yet, but I should say that the efforts that have been tried so far have aimed at a regression histologically of cirrhosis from the histological stage that for too long.
So logical stage.
Three.
This is considered to be a high end.
And what matters for patients and for the outcome is actually.
How how the disease progresses, and slowing or reversing the disease progression is actually both the mattress.
Regardless of the outcome of patients is also corresponding dear.
The guidance of the FDA, which I think makes a lot of sense. The FDA has does not recognize the solar.
Electrical endpoints in cirrhosis patients.
Surrogate endpoint.
They actually did.
By an upcoming improvement in.
And that she royalties of course, both Nash and so it all just sort of diseases driven by all the parties have Nash and then the.
<unk> miserable cereals itself, so I think in that regard.
A lot of Citron off has a very attractive.
Position and very good.
A question on I think to study some of you better in.
In patients with Nash cirrhosis, because it doesn't affect not just if it does affect capitals of course, but not only fibrosis. It has an effect on all the other pathways that drive this disease metabolism.
Inflammation et cetera, it's well known that patients who have type two diabetes. For example, the nationals progress much more faster so the underlying metabolic abnormalities continue to play a role.
On the on from.
From the FDA is Angola has made a couple of public announcements.
Confirming what I just mentioned about the.
No no.
Astrology histological improvement of Nash cirrhosis B.
Hi, Bob.
And also not being a surrogate endpoint, but on the other hand.
Offering a outcome improvement in Nash patients as in the.
Path to full approval path to full approval that was also a pivotal non cirrhotic Nash assuming debt bonds has received accelerated approval for.
Pre cirrhotic Nash.
That's actually a very good.
Plan or strategy from the FDA I think it makes a lot of sense and of course the euro.
Thinking along those lines and you know well.
Seek our interactions with the FDA on that topic and consultancy. So I hope that addresses your question I think a proof of concept study in psoriasis is as well.
Quite difficult because you have to then a no vote.
And the point.
Proofs of concept to reality is that instead of just there's not really one such endpoint.
So I think the.
Great.
A lot of headroom.
In all of these possibilities.
Drive cirrhosis as a pump peptide agonist strikes and indeed these are receptors, that's really havent programmatic effect on the spectrum of disease manifestations.
I guess it was a very strong very good professional I think to look at the outcome.
Improvements with Islam.
With love it or not in Nash patients with cirrhosis and that's our current line of thinking.
Thank you my opinion, the last question about the power solar power.
Answer is.
It's just the fact that it's just proven more time consuming than anticipated to find a solution for.
That meets our objective, which.
Certain signs are quite simple.
First objective is to add to that.
Hope is to find an option of solution.
Ensures that the parcel continues to be developed.
And the NPS.
NPS expansion because there is really neat.
In this circumstance, we owe it to this patient.
Secondly, also solution that ensures.
Certain return.
Financial gain for <unk>.
Because otherwise if you do not meet these two objectives.
Better off.
We are keeping.
The land parcel.
For our self and once we have the time and resources to get back to work and get back.
And get back on developing a depart.
So that's the that's why we want to have more time to see what is the best option for the powerful moving forward.
Alright, thanks for that.
Thank you. The next question is from the line of Ed Arce from H C. Wainwright. Please go ahead.
Yeah.
Great. Thanks for taking my questions.
Congrats on the initiation of a native story.
A few questions for me firstly.
<unk>.
You mentioned there are other areas in other trials that are.
Part of your overall programming, you're considering so firstly.
With the ongoing phase III.
It is expected to read out early next year.
Type two diabetes.
If you could just.
Explain.
You're thinking about that is that.
An area, where you believe ultimately could lead to a supplemental NDA perhaps.
<unk> expansion EMA or how do you see that program ultimately.
Evolving and then turning to combo studies.
Which particular mechanisms.
Do you believe make the most sense for let me put the Nord.
And you know what what areas specifically, what you think makes the.
The most strategic sense.
And then.
Turning to the native three Ah study.
Of course, you know, there's a key differences with the phase II b.
Longer treatment.
900 patients.
And it's only up two or three but I wanted to.
Hum.
To just focus on any of the other key differences.
Beyond those because I know that.
A lot of the thought behind it was to try to.
Replicate as close as possible.
Yeah.
The baseline of the phase two b.
And then I have a follow up thank you.
Thank you Ed maybe.
For the question about the QC.
The objective of this study outlet.
The Purion serve Medicare can also cover the.
The rationale for developing <unk>.
Combination study in which making those action would make it suited to be combined with <unk>.
And for the design of the Phase III, Michael if you Didnt can take that will be it would be great.
Sure.
Okay. So thank.
Thank you for the question. So the phase two QC is more I would say an exploratory study that would lead to a mechanistic data it actively to them too.
Submissions have actually nothing she'd been though in improving.
Sydney sensitivity.
And this is really something that.
Mentioned conditional shapes and if you've been north from.
From several of our competitors and I think as these key also for them.
<unk> is a condition of Nash patients.
I would say that it's.
Something which is really where it's a study that is truly mechanics each.
Understanding.
Thanks.
You can see.
Of course, this would be supportive data to.
We brought to the attention so he can actually annuities.
When deciding.
NDA for the treatment of Nash and improvement of fibrosis.
<unk> specialty C suite.
The two divisions.
Yeah.
So that is the in the restaurant for this study which is currently ongoing.
Relatively to your question on combination therapy, So I think I'm.
Very interesting community sounds like she then should be no plus as you choose.
In the midterm.
It kind of clearly.
Pools over to you and if you could see a dose issues do we need to dose, which you probably know most who've been investigated.
In type two diabetic patients with Nash with you on Nash.
Plus it does exclude the potential.
Potential to offset the weight gain that we'd see.
Some patients treated with <unk> should be north.
With the due to the mix effects enough as you two inhibitor suites, which is actually a.
Using the <unk>.
Both of course, which is which.
Which can be used for being stored.
Due to the increase.
The output of glucose triggered by inhibiting CMT two plus.
Maybe.
Is it between us and so far have been proven to be very safe.
To reduce our well to have another outcomes.
It comes off on cardiovascular events.
So there is a quite a strong rational for.
Developing these.
These two products.
Moving this combination I would say.
So this study that we are currently working on and of course as soon as we would have some explaining that I used to design something that we'll share with you.
Yeah.
Yeah.
Well Michael.
Yeah on the question on the differences between Natus and native and three the phase III study.
The main difference is the duration of treatment, which I think is actually to the advantage of this study.
This was a healthy 24 weeks and we did see as you.
The dolphins of data clients and a strong effect on fibrosis, which is actually.
Not always the case right fibrosis histologically lacks behind and after.
Often in.
After these effects have been seen that would have required a longer duration of treatment. So six six months of treatment actually is a short duration to see an effect on the histology, which.
Reaffirms actually the efficacy of not my favorite or north.
The longer duration should sort of course play.
Enable us to see these effects on fibrosis.
More importantly.
Importantly, more strongly that's the expectation.
And I think when we look at the multiple Biomarkers. If you looked at what we can expect to see a movement.
Movements in these biomarkers.
Flex fibrosis.
Should translate in a strong histology wasn't down the road. So that's the main difference.
You mentioned that the patient population is more strict with regard to the staging of fibrosis F. Two F prevent us in Natus.
All fibrosis stages were enrolled other than at four.
That is true we have looked at.
We have done an analysis of course of patients with <unk> compared to the total population that NATO centuries, essentially no difference so the efficacy.
It remains the same when you look at T F. Two F Street population.
Studies so that's.
Reassuring that to the phase III study to actually.
Natus and that's you know all of them as I mentioned before the patients who do have a certain degree of fibrosis advancements are the ones who are.
Require treatment.
Most.
Most.
Most are in medical need of treatment.
I think by and large we have.
We have.
The benefits, we expect to benefit from the longer duration of treatment in the phase III study and other than that most.
Factors have been.
Kept as stable as possible.
Great.
Sorry go ahead.
So I hope that addresses your question.
Yes, that's very helpful. Thank you.
And if I may one.
Further follow up regarding.
Regarding severe regard.
You mentioned, the JAK class and of course the.
The safety issues that have recently come up.
With us class I'm wondering.
Given.
<unk>.
The novel Class that are saved Aragon Zen.
There are there.
Particular classes or other drugs in development that you see particularly competitive given the overall profile to date a severe oregon.
I think if you look at the space of course.
Although two will.
Will.
Will evolve, but there'll be a class two to follow.
But it said that we have not indentified.
The compounds or.
Mechanism of action they can.
Roche.
Tangible.
Once daily.
Overall <unk> gamma.
Yeah.
Thank you Rudy.
Thank you. The next question is from the line of SEC <unk> from Roth Capital Partners. Please go ahead.
Well thanks for taking my questions maybe the first one for me just a follow up to the last question regarding a teacher development.
And I just wanted to clarify if the plan is to use the same doses that you're currently using for both the combo and what the FBI patients because I imagine that would impact the development timeline.
Well no concerning on doses, maybe speaking under the control of care or Michael if he gets a bit too soon to.
And if the project our self on what day or what are the doses that are suited.
Either if we decide to develop a fifth campbell or that are suited for four developmental.
Let's first focus on the current phase III and if two or three and then once we have our plans.
For the other fixed dose combo or floor will okay.
Can communicate on the adequate dose.
Thanks, Paul and then the last one you have for me and I think I've asked this question before but again just wanted to clarify for your site. They are currently using are there ongoing studies.
And then again how are you planning.
Brandon to kind of differentiate Randy.
Or how like doctors differentiating Danny.
Sometimes the recommended patient or you are studying or pardon me.
I'm dialing it back inside.
Mhm.
Yeah, maybe Michael take that.
Ed.
Yes of course.
Nash is a very competitive field as many others.
Diseases that represent the medical need of call. So it's not unique but it is very competitive.
Yes.
So there are a number of studies in different stages of development.
And therefore, most sites that have experience in Nash do have other studies, that's obvious and.
How do you differentiate.
It's it's a it's a number of factors strides.
First of all I believe the most important argument is the fact that a lot of people notice.
Promising compounds to reach the market its efficacy data.
That being said he and that safety profile has been a very convincing to the community and whenever I speak with herpetologist in different parts of neuro and so they have.
A lot of shipping orders on the radar screen very clearly.
The risks and the.
Demand for a compound like <unk> or not and it has to do with the fact that it is.
I can't keep an agonist that it really addresses the pathophysiology of Nash at all levels and that's not something that all compounds do I think that is an advantage. So we also as you may see from.
Publications that we.
That's been.
Presenting at Eagle recently.
Looking at our data in the phase two study in native.
Honestly I don't know hesitancy.
Very convincing efficacy on all markers of cardio metabolic health on.
That's good let's see me et cetera.
So these are important differentiators, we treat the liver disease, but also the entire spectrum of what constitutes metabolic syndrome, where they come from flagstone a syndrome.
And pathologists are physicians who are.
You don't see in these patients a day no debt and they they are at least hit that and I think that gives us leverage of course leverage does not come by itself does not make us complacent so we'd do.
We're fully aware of the.
The fact that there are other compounds, which are also attractive and so we are we have.
We.
We will continue to be present scientifically.
We work on good working relationships with our.
Colleagues investigators to different sites together with.
Our partner so we have freely.
Every day that you have to earn that leverage if Jewish and that is part of the efforts we do too.
Having very efficient operations aspect of the study which includes multiple levels of how we interact with the sites and then.
Keep it goes without king's relationship, but I think the.
The core of all it is really the strength of our.
Fluffy Bernhard and how it addresses the disease.
Thanks, Michael.
Yeah.
Thank you one more question on the science and this is from Intel and away from Societe Generale. Please go ahead.
Yes, hi, good afternoon, everybody. Thank you for taking my question.
I was wondering Kim Jong Yoo from the Abbvie team.
Team was daunting.
Thank you Kevin I'm wondering.
Do you have any view on the dosing that's going to be.
Okay.
We treat those people.
P J Keating.
Hey, Jim.
Phase two trial.
Any chance that one of them.
Yes.
Getrich patient do you have any view on that.
So the Nintendo Nekoosa candidate <unk>.
In general <unk> shall exceed the guidance.
<unk>, Michigan attached to them.
You get an idea if it.
Let's say common recounting the scanner to the deputy coating.
According to revenue.
And we have to keep in mind.
Regarding guidance.
We had some <unk> two times.
Previous to the end of the Christmas.
Well it could be through communication and do you have any idea on the way you're going to communicate regarding the number of patients to date.
In Q into the trial.
You remember that previously you were also communicating a member of the.
Opening sites are.
Queen patient recruited patients is something that you can continue.
You're going to you're going to say you know basically at the end of the 900 patients.
Just wanted to get an idea.
Okay.
We had a previous question.
But I do understand your response, but I was also really wondering what he knew that makes you think that to me.
As a different proposition than the one you have in hand.
So.
In the next couple of months, because Dave no new clinical data I guess revenue interpretation of data.
What is the.
Yes.
Would trigger additional year.
That strategic review and finally, Ken gave guidance on the oncology pipeline and they got Ted.
Program that you may have.
Thank you very much.
And if you didn't think so.
First question about the <unk>.
The oh cause wherever with Abbvie of course, we.
Uh huh.
Of course, a good relationship and then we have the.
Contractual communication the GSE.
Oh.
Allow us to have access to.
To the.
Zero again.
Otherwise it must be clear that in terms of development strategy.
This is fully in the end of a visa totally in control.
And I have to say that I think this is a great advantage because when you talk about.
Which is a company in the world that can you.
Developed successfully.
Compiler raw Guy mine deal to an immune disease space and who have strategically motivated to do so I think all the abbvie of course coming from on top of the list.
Directly on your question about the pediatric frankly, I don't know.
Nevertheless, but that's my personal opinion that they would have to run a specific.
Ah study in pediatric patients.
Hum.
But Glenn you recruitment.
So I think.
What is I would say required by them by the stock. It's changed so you know if we are delayed we believe this is a.
Materially formation, we will have to communicate on that otherwise.
Will we.
During the recruitment period make regular updates we we haven't decided on that we also need to be careful about competitors. So we have not taken a decision.
And otherwise, we'll also have to communicate them to the SMB and of course the safety ever.
You know something unexpected.
That comes up.
They don't know the parcel.
You know the CEVA evolve.
Competition can evolve.
We also have the planned meeting with the FDA to discuss.
You know who to validate.
What it would take to get this product.
On the market. So this is probably an information that Ken.
Trends in our.
Our package.
Otherwise you're right in terms of all the data.
We are not planning to.
We've developed new data.
Worth, noting human not didn't look preclinical.
And then on the up there I would turn to Pierre because indeed there feet.
On the Epo pathway Youll have some exciting developments.
Certainly.
And oncology targets that is getting more and more attention.
So just so two other annuity books or wherever.
Papers submitted.
Being reviewed that Wilkes who.
Hum.
Sure some some some interesting technical information.
To be published.
I think you will see.
An important step and regarding Europe pizza.
As you go down to two by the companies that have been.
Working on this program.
You've actually on Qunar.
Busy these days.
Comparing the two.
A core part of our compounds, we let's see.
And we see that.
I hope familiar Europe, but eventually all hubs.
Coupled in a bit.
The contact of the beats.
Between Europe and Kid.
Yep.
As a kind of fun.
Suddenly the member which is very close Cortez that can actually Oh.
Be activated when you have T. D's, you visit and we have some data showing that the World Cup.
Innovating booths, yep, teed and tested which makes this the.
Profit for a compound very different from us.
So thats been published but you don't see and of course the opportunity to target.
Many other cancers.
We're currently working on this particular type of compounds.
The PK profile of those two.
In addition to.
We went to them in vivo studies.
And I think they'll finish the question for sure but can you repeat it again I was wondering regarding the.
Mike.
<unk>, sorry, the <unk> run rate and to scale up.
Up to the double digits.
I don't know if its something that I can't remember is established.
Communicated with the AML.
So you're talking but the level of sales targets itself is something that.
We haven't come in with the rest of the industry that are progressing well.
Right.
Thank you definitely know what we can say that first of all we cannot disclose anything about the conditions, what we may send the bullet point.
Where do you think is that is it.
Is reasonable if I may.
I said to reach.
Double digits, it's not something which which could be considered a very aggressive but.
The market.
We grow and how the launch.
There is the approval of <unk>.
Behave, but I mean, it's quite balanced and.
Okay.
Possible to reach okay.
Thank you thank.
Thank you very much.
Yeah.
Great.
Some question on.
Online.
So as I can feel from Bryan Garnier several questions. So I'll try to address the first one concerns the ATM.
And the question relates to the fact, if we raised <unk> hundred million with the ATM is that totally signed into phase III, but I would say that first on the ATM. This is an opportunity that is available to companies opened on the NASDAQ and its clearly something we would we wanted to benefit because it.
GAAP and some long term investor called back to us they want to buy you do they want to build a position they are not allowed or not allowed not.
Unable to do that because the liquidity is limited.
That case, we view that as an opportunity to give us some financial flexibility, but we have not decided to use the full amount of the $100 million.
And yes, if we ever raised 100 million then we continue with the other options we are studying like loans like or a partnership.
There is a high likelihood that the phase III will be.
Fully funded.
Then so shackled to ask about you know the partnership discussion we have had discussions with potential partners.
Of course, I cannot go into details but of course, if we look at the Nash space remains.
An area totally unmet with high potential and if you look at the drug that they have shown the <unk>.
Promising results that I've met.
The two regulatory input from the FDA, Let me really stands out of course with the discussion with potential partners, but always.
First with the option that we do it on our own and secondly, clearly we think.
<unk> tends to make it to the finish line. So we want to keep.
Lotto for where we want to keep downstream value, especially in the U S market. So this is for us a non negotiable.
Which we which we have and this.
This is something that I think is important for all of our shareholders.
And then a question from Zack concerning figure again.
More specifically the fact that there are out there a compound like <unk>.
That only require three or four injections per year.
Therefore, maybe or develop more oral drug it might not be such a.
Such a panacea.
The solution.
I would say.
First.
The objective of.
<unk> is also 12 and efficacy that is similar to humira.
If we look only at the psoriasis area, we see your Tesla, but that's certainly an efficacy that is.
I wouldn't say minimal, but reduced compared to two IL 17 or compared to your mirror and still with Tesla.
<unk> 2020 more than $2 billion. So there is clearly.
The position or rolled for neuro drug and then finally, you know abbvie is commercializing SKU easy, but they are still very much motivated by.
By zero until their most definitely be a place.
For for for this drug.
So this I think cover.
The question from Zack and then with one last question that tackled the R&D expense and if we can give some projection about 2022, so I'll turn to to show for that okay. So as you know we cannot disclose any projections, but you know.
Where do we stand today in terms of the face we will maintain.
We did not sign the contract John first with this year will see demos so.
This year, we will not have a full year basis in terms of expenses. So mechanically late next year, we should have.
<unk> increased to take into consideration.
A full annual basis also.
Also including you know.
The full year of our.
Operation.
So I must say that it would be in continuity slightly increasing for next year.
Thank you you also discover.
Hum.
The Q&A session I would like to be up with ultimate team. Thank you for your support and for following us over.
For the past year and now of course, we look forward to provide additional exciting news with our with our pipeline <unk>, Oregon to the parcel in our school yet.
Well, thank you very much and have a great day.
Okay.
Thank you that does conclude the conference for today. Thank you for participating and you may now disconnect.
Oh.
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Okay.
Thanks.
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