Full Year 2021 Inventiva SA Earnings Call

March 8, 2022

Good day, and thank you for standing by. Welcome to Inventiva's 2021 Full Year Results presentation.

At this time all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded and if you require any further assistance, please press star zero.

I'd like to turn the conference over to your first speaker today, Frederick Fran. Please go ahead.

Thank you and welcome everybody to the full year financial results presentation.

As tradition, I would say, I would share the floor with Darrow, our CFO .

Sure.

Michael also will present the clinical studies, the phase two we've done by Professor [ ] and the legend study well Pierre will cover an update on the phase III.

The clinical studies the phase two.

We've done by Professor <unk> and the legend study well Pierre will cover an update on the phase III.

And then we'll end up with you all of our CFO will give more granularity on the CCAR.

The CCAR.

But before we go into the details of the clinical update, I just would like to provide some of the key highlights of 2021, which I think has been when you look at everything that has been achieved, quite successful. If we start with lending.

Clinical update I, just would like to.

To provide some of the key highlights of 2021, which I think has been when you look at everything that has been achieved.

Quite successfully so if we start with lending.

So we are committed to start the native for phase III pivotal study, which we did. On top of that, we also announced the design of the legend study our combination study between [ ] and [ ] two inhibitor and disclosing it this morning. <unk> seen that we have received positive feedback from FDA and the IND application has been accepted by the diabetes division.

And on top of that we also announced the design.

The legend study our combination study between <unk> and <unk>, two inhibitor and disclosing it this morning.

<unk> seen that we have received positive feedback from FDA and the.

<unk> has been accepted by the diabetes Division.

The interaction with FDA I would say overall during the year has been very positive.

During the year has been very positive.

So my lights are certainly the fact that the past drug, which we had secured for patient with two or three has been extended by FDA to cover patients with compensated cirrhosis.

We're also extremely pleased by the information the feedback we got from FDA and thirdly, the Tox package, which FDA considered as adequate and complete to file an NDA in Nash.

To file an NDA in Nash.

This is extremely positive because it means that we've take other thoughts in the way to commercializing land.

Way to commercializing.

Sure.

We also continued to prepare and complete our package for filing and we positively concluded a QT QTC study, where demonstrated no impact on current electrical activity.

And finally as you all know we had this fantastic publication by the New England Journal of Medicine of the study of the phase to be native title.

So that's the highlight for lending, but then I would say 2021 for us was the year of the Oregon with the completion of the Phase 1B and especially.

Yes.

The completion of the phase one be and especially.

we're very proud and excited to see how it has been moving forward with this trial confirming that they've seen mirror-like efficacy that they believe that could be an efficacious drug in psoriasis and their decision to move.

Mirror like efficacy that they believe that the.

<unk> could be.

An efficacious drug in psoriasis and their decision to move.

Pleased to be because the data of Phase 1B where available in April and I think in November 5th to be started, so that's quite a fantastic accomplishment by the clinical team.

The <unk> clinical team.

And that of course is a direct translation in terms of finance because it triggered before million milestone when the first patient in the Phase 2B was in the study.

<unk> in the study.

With the power solar, we continue preparing for a meeting with the FDA. The objective is to validate with FDA the design of the pivotal trial, which we think is key in finding a new home for all day parts.

Preparing for a meeting with the FDA. The objective is to validate with EBITDA. The design of the pivotal trial, which we think is key.

Finding a new home for all day parts.

Other highlights, less visible we opened an Inc. in the US where we also now an important, sizable cleanup team to follow our native Phase III study.

Back less visible we opened <unk>, Inc. In the U S where we also now.

Important to sizable cleanup team.

To follow.

Our native phase III study.

We also reinforce the team with several recruitment in all departments and also going forward the board with the arrival of dilemma. The financial social will cover that in detail, but we are very pleased of being able to activate at the natural market program of a total envelope of $100 million approximately $30 million is already being used to satisfy the reverse inquiry of long term investors.

Martin dilemma on the financial social will cover that in detail, but we are very pleased of being able to act.

And at the market program of a total envelope of $100 million approximately $30 million is already being used with.

To satisfy the reverse inquiry of long term investor.

And the cash runway, which run through Q1 23, but this is my quick intro and now I'll give the floor to Pierre who will give you a brief update on the Lendingtree brand.

<unk>, which run through Q1 2003, but this is my my quick intro in now.

I'll give the floor to Pierre who will give you a brief update on the Lendingtree brand.

Okay. Thank you Fredrik.

So, we're now moving on page 10.

So as you know, LendingTree of noise, a pan agonist in clinical development Phase 3 for the indication of treatment of Nash and improvement in liver fibrosis.

It has an unprecedented structure and pharmacological profile, it's a pan agonist with moderate and well-balanced activity across the street reforms.

Sedan structure and pharmacological profile, it's a pan <unk> agonist with moderate and well balanced activity.

Across the street <unk> reforms.

It's not entitled and it's not a fabric.

You're very much aware about the number of preclinical investigations that we have performed and showing that most if not all of the pathological features of Nash can be addressed by the north through the activation of several people. Our ISO forms for example.

And showing that most if not all of the pathological features of Nash can be addressed by the north through the activation of.

Several people are ISO forms for example.

The Delta and the Gamma activation, we think is really important and leads to the strong anti-fibrotic activity of the compound, whereas the reforms are involved in the inhibition of inflammation and ballooning.

And leads to the strong anti fibrotic activity of the compound, whereas the <unk> reforms are involved in the inhibition of inflammation and ballooning.

And the potential of Lendingtree, even though to address most if not all pathological features in Nash has been as you know validated in the native Phase 2B trial in non patients and the results of the study actually supported. Breakthrough therapy designation by FDA, which came on top the fast track designation that was already granted for Lendingtree below.

Breakthrough therapy designation by FDA, which came on top.

The fast track designation that was already granted for Lendingtree below.

Sure.

From a safety point of view as you know the non clinical Tox package, which actually included long term studies up to two years, so that LendingTree, even though had a Good safety profile.

Two years, so that lendingtree, even though <unk> had.

Good safety profile.

And FDA confirmed that the stocks package is complete and acceptable to support the filing of a new drug application NDA.

Is complete and acceptable to support the filing of a new drug application NDA.

[inaudible] in the clinic is also a favorable tolerability profile.

Evidence as of today, now and close to 500 patients or healthy volunteers.

As of today, now and close to 500 patients or healthy volunteers.

So importantly, this year, we have completed a thorough Qt QTC study.

Which is a standard component of all clinical development programs for any new therapeutic agent in support of NDA.

These kind of studies of interest in the context of the targeted population.

As the QTC interval prolongation is common in patients with liver cirrhosis.

So, the design we used was the one we commanded by FDA.

And intended to consistently identify drugs that may cause Qt prolongation.

And in this study repeated daily administration of [inaudible] dosed up to two fold higher than the maximal therapeutic dose had no effect on the Qt interval.

In this study, which meets the FDA requirements therefore confirms once more the safety of Lanifibranor

The FDA requirements therefore confirms.

Once more the safety of lending should manure.

On Kodak activity, which was previously observed in our phase two studies.

So if we move to our next slide.

So following the successful outcome of the native phase III trial with Lanifibranor in Nash.

We have agreed on our phase III study design with FDA and EMA and this study is now initiated.

And this study is now initiate it.

To complete the clinical development plan of Lanifibranor in Nash and besides the study in collaboration with Professor Choosy.

And besides the study in collaboration with Professor Choosy.

Evaluating the effect Lanifibranor on liver insulin resistance. We have also initiated an additional profiling study in Nash patients.

Which is going to evaluate the potential of Lanifibranor to be used in combination with [inaudible]

In combination with <unk>.

In Nash patients with type two diabetes.

Next slide.

So the key dates that lead to these three studies are the following.

<unk> lead to this.

Studies are the following.

We expect the results from the part one of our phase III in second semester 2024.

Our phase III.

Second semester 2024.

The result of the study on liver insulin resistance in [inaudible] patients with type two diabetes will come second semester this year.

Study on lever insulin resistance in patients with type two diabetes.

We'll come second semester this year.

And the results from the combination of Lanifibranor, plus[inaudible] in Nash patients with type two diabetes will come second semester 2023.

We'll come second semester 2023.

Next slide please.

So to happily recap on the design of the phase III.

So, in terms of inclusion criteria, we are fully aligned with the patient population that has been included in the NATIVE phase 2B trial.

We are fully aligned with the patient population.

Has been included in the native phase two B trial.

Simply the focus is more on if two out of three patients in the native cease to be.

The patients will be included in the study when showing an activity score. So, combined score ballooning inflammation, which is going to be equal or superior to three out of four.

Included in the study when showing.

And activity score so combined score ballooning inflammation, which is going to be equal or superior to three out of four.

And as I mentioned the Fibrosis score is two out of three

Sorry to NFC.

The patient population will be stratified on type two diabetes.

[inaudible].

It's of course three arms, so we'll be evaluating two dose of Lanifibranor $812 million that were investigated in phase 2b trial.

The statistical powering is 90% and the central biopsy reading process has been agreed with regulatory authorities and will involve review done by three pathologists.

Been agreed with regulatory authorities and will involve review done by three pathologists.

Next slide please.

So the end points for the first part which will last 72 weeks and will include 900 patients.

Which we lost.

72 weeks.

And we'll include 900 patients.

This primary endpoint is the composite endpoint of Nash resolution and no worsening of fibrosis. Meaning that the patient would be qualified as a responder if he shows both Nash resolution and improvement by one stage of the fibrosis score.

The patient would be qualified a responder.

So both Nash resolution.

An improvement by one stage of fibrosis score.

And as a reminder, in the NATIVE Phase 2b study.

In the population of patients with F2/F3 fibrosis score.

<unk> score.

The placebo with 7% and the number of responders in the low dose with 24%.

7%.

A number of responders in the low dose with 24%.

For the high dose 33%, therefore, three and four times more responders in the treated arm relatively to placebo. This was in the NATIVE phase 2b trial for this same composite endpoint.

Composite endpoint.

Our secondary endpoints of course, we will have Nash resolution and no worsening of fibrosis.

Improvement of fibrosis, and no worsening of Nash and other endpoints will include the glycemic control improvements in renal function and reduction of cardiovascular risk.

As a few examples.

Next slide please.

So relatively to the second part of the study, the endpoints are actually based on time to first clinical event.

Second part of the study.

The endpoints are actually based on time to first clinical event.

Which can be defined by either historical progression to cirrhosis or cause mortality.

All cause mortality.

Decompensation events.

The meld score equal to or above 15, and/or liver transplantation.

Next slide please.

So where do we stand today? So, the study is conducted with us by Icon and two clinical research networks that are specialized in Nash Summit in the U S.

With us with by icon.

And two clinical research networks that are specialized in Nash.

In the U S.

And AS in Europe .

In Europe .

Today, we have 350 sites qualified.

The study has been approved in 11 countries out of 25.

And the regulatory review is ongoing in the 14 remaining countries.

We have 121 sites activated.

Among which 77 in the U S and 44 in Europe.

In Europe .

As you can understand, due to the current circumstances in Ukraine.

And circumstances in Ukraine.

All clinical sites in Ukraine, and Russia has been put on hold.

And we are currently working on a mitigation plan with Icon to activate additional sites in other countries in order to compensate for the missing recruitment in those two countries.

Working on mitigation plan with icon to activate additional sites in other countries.

Order to compensate for the missing recruitment in those two countries.

Next slide please.

So we are also actively working to put in place an efficient and secure drug substance and drug product commercial supply chain worldwide moving forward.

An efficient and secure drug substance and drug product commercial supply chain worldwide moving forward.

And for the drug substance, we will have two major cmo's involved.

Both FDA approved with industrial capacities, ensuring the supply in the U.S., Europe, and rest of the world.

With industrial capacities, ensuring the supply.

U S Europe and rest of the world.

And likewise for the drug product.

In parallel, the pharmaceutical development plan in support of the commercial supply has been defined with them and this is for both drug substance and drug product.

So, with this I would like to hand over to Michael. He will go through, based on our first study in [inaudible] patients with Nash collaboration with [inaudible].

Based on our first study.

In.

<unk> patients with Nash collaboration with <unk>.

Please, Michael go ahead.

Thank you [inaudible].

[inaudible]

As further support and profiled almost hit or not with regards with efficacy in patients with Nash and also patients with type two diabetes. First starting on slide 19 is a study in patients who have Nash and [inaudible] and type two diabetes.

Also patients with type two diabetes.

First starting on slide 19 is a study in patients who have.

<unk> study in <unk>.

Patients who have.

Nash and Nash.

Type two diabetes.

This is really a study to further understand the mechanisms.

The mechanisms.

How long of shipping.

<unk> is a bumpy path agonist.

On several aspects of these metabolic diseases.

These metabolic diseases.

So, the primary efficacy endpoint is the reduction.

Patrick.

And simulation so.

I think Pat.

And also we look quite in depth in how this is associated with changes in adipose tissue and insulin resistance in the main organs.

So in resistance in the main organs.

Fat tissue, liver, and muscle these are all affected by metabolic diseases.

Ever.

So these are all affected by metabolic diseases.

And also, to look at the broader picture of how the cabinet metabolic risk profiles.

It's a broader picture of how.

The cabinet metabolic risk profiles.

Microsoft coupled with public health.

Patients with type.

Type two diabetes are beneficially et cetera.

By and large it or not.

As a background.

I'll now call it selling lipid diseases Nash and type two diabetes.

Underlying income and underlying disease biology, and so in many.

High percentage overlap, 70% respectfully.

Yes.

Hello.

The more estimates, the more progress these diseases become the more we can find that they coincide. They work together. And that has to do with the fact that patients have diabetes, Nash is more severe and vice versa.

Progress is as he has become the most we can leave <unk>.

Coincide.

Together and that has to do with the fact that.

Diabetes.

Patients have diabetes Nash is more severe.

So there is some interaction between the two conditions.

So, in diabetes itself becomes more difficult to control in patients with Nash and needs more medication substantial proportion of patients who will have more severe form of.

In.

Diabetes itself becomes more difficult to control in patients with Nash and small dedication substantial proportion of patients who will have some more.

Cynthia form holding with that.

<unk>.

Desktops of pesticides versus described as ballooning inflammation of the liver.

Yes.

And the progression of fibrosis towards cirrhosis, more severe, and progress is more rapidly in patients who has also type two diabetes.

Most of the year and progresses.

Rapidly on patients who are <unk>.

<unk> also type two diabetes.

The coexistence of these two diseases has also to do with the severity of saline resistance in multiple organs and then set to suit adipose tissue insulin resistance actually leads to the inability of fat tissue to store.

Also to do with the unity of saline resistance in multiple organs.

And then set to suit adipose tissue insulin resistance actually leads to the inability of fat tissue to store.

Inability of fat tissue to store.

So just trying to get more increased. A lot of fatty acids and delivery strength is the cause of them.

Increased lot of such assets and delivered which Tim.

is the

Of course, some LIFO.

LIFO toxic and vitamins and delivered which contributes in fact to the damage of liver cells and resulting inflammation.

Of liver.

<unk> ourselves and the resulting in summation.

Insulin resistance again then leads to the inability of the reduced ability of the liver to secrete very low density by proteins.

Inability or to reduce the ability of delivered to <unk>.

Very low density.

Proteins.

Increases de Novo lipogenesis altogether, leading to what we call atherogenic Dyslipidemia profiles, which explains increased cardiovascular risk and that's why these patients have elevated triglycerides, low levels of beneficial HDL cholesterol levels, and small dense LDL particles.

Explains increased cardiovascular risk and that's what <unk> patients have elevated triglycerides.

Hello.

Low levels of beneficial HDL cholesterol levels and small dense LDL particles.

Slide number 20.

The study that we're conducting with Dr. Causing in Florida. He is the investigator and also the sponsor.

It's a small study as I mentioned details further.

As I mentioned details further.

The mechanism of action of panel shipment and also totaled 34 patients are involved. They have type two diabetes and it has to be not ( ), but in certain limits of course, so they will each be able to see not to be higher than 9.5% this should not be on insulin or should not have pumps within the last year and they have to have all (D), which is diagnosed noninvasively for this study.

Not.

Also within certain limits of course, so the HP able seats.

Not to be higher than nine 5% this should not be on insulin.

But let's just all the pumps.

And Thats, all D, which is diagnosed noninvasively.

The study.

They have to have at least 10% determined by MRS.

Patrick.

Such.

Determined by <unk>.

Yes.

And if they have a stable weight, which is defined as no increase or decrease of more than 5% before the study stops then any number of investigations state of the arts and that will define a quite comprehensive picture of the metabolic effects beneficial effects step level of shipment has in these patients.

No.

The decrease of five.

5%.

For the study stops and then Donato any number of investigations state of the ops.

<unk> quite comprehensive picture of the <unk>.

Metabolic effects beneficial effects step level of shipments.

In these patients.

So somebody will do ultrasound-based imaging, travel scan to evaluate for liver fat and fibrosis, we looked at MRI measurement of fats, PFS. as well as fleet fibrosis.

Measurement of PFS.

PFS.

Let's talk about fleet.

<unk> fibrosis.

The study also includes some advanced correct T1 MRI mapping, which provides a picture of inflammation and fibrosis in the liver quantified picture.

Advanced correct T. One.

MRI mapping, which provides a picture of inflammation and fibrosis in the liver quantified.

Picture.

There are additional tests that will define the degree of sensitivity using Saracenic plant and seline section steps enable us to measure the initial degree of influence sensitivity and the improvement thereof felt a lot simpler and then a number of smaller steps altogether in correspondence to cardiometabolic health market HBA, we'll see.

Additional tests that will define the degree of sensitivity using them.

August Semic plant.

Sexual steps.

<unk> enables us to measure the initial effects.

Initial degree of influence sensitivity.

and the improvement thereof felt a lot simpler and then a number of smaller steps.

And altogether chorus.

Corresponding to cardio metabolic health, Microsoft plus seem yes.

<unk> Marcus HBA, we'll see.

Connecting and so forth and also a panel of market fall and liver fibrosis.

So.

The main imaging and metabolic results were based on spectroscopy intra hepatic triglycerides.

Spectroscopy intra hepatic triglycerides.

MRI-based fibrosis measurements and inflammation fibrosis with the correct T-1 measurement.

Inflammation fibrosis with the correct T. One.

Measurement.

Insulin sensitivity through lab tests, and then profile of catametabolic risk factors and fibrosis.

Lab tests, and then pulled off.

Catherine metabolic.

Thanks Hunter roles of smartphone.

Slide 21.

I mentioned that the principal investigator Dr. Cozy at the University of Florida has a study for patients who are randomized one in one to placebo or active which is the 800-milligram launch date.

Florida.

has a study for patients who are randomized one in one to placebo or active which is 800 milligram launch date.

Date.

And in addition to that in order to have reference value for each evaluation, specifically for the imaging tools that will also be healthy none of these individuals will provide these reference tests for metabolic and imaging tests.

Evaluation, specifically for the imaging tools.

that will also be then.

Healthy none of these.

<unk>.

Probably provide this.

Tests for metabolic and imaging tests.

The sample size is calculated based on an expected effect size on the intra hepatic fat cultural triglyceride content.

Okay.

We have data, which we published previously of the effect of cultural triglyceride on the hepatic Steatosis histologic and also capped fiber scan so that provides reference for these sample size calculations.

The published previously of the effect of <unk> on the hepatic Steatosis histologic, yet also capped.

Fiber scan so that potlatch.

Smokeless sample size calculations.

The primary efficacy endpoint is based on a change in the inter hepatic triglycerides at the end of treatment, which assess totaled six months week 24.

At the end of treatment, which assess totaled six months week 24.

Based on expected effect size and then a broad panel of secondary endpoints that's as I mentioned before we'll look at key metabolic markers associated with type two diabetes insulin resistance.

I mentioned before we'll look at.

Key metabolic markers associated with <unk>.

Type two diabetes insulin resistance.

Proportionate for sponsors defined as the percentage of patients who have a decrease in intrahepatic 30% or more.

Scientists the percentage of patients who have a decrease in that.

Just shy of.

10% or more.

The percentage of patients who have a resolution of Nash defined as patients with less than 5% hepatic triglycerides at end of treatment changes in hepatic fibrosis measured at different quantified the different tools MRI.

<unk> quantified the difficult tools MRI.

MRI fibroscan, biomarker, and of course also the safety evaluations. The study is ongoing.

Safety.

Elevations study is ongoing.

Dr. Cozy expects the study to be completed by the end of this year.

No surprise that the enrollment of patients has suffered from the Covid pandemic until recently.

From the.

Covid pandemic until recently.

But.

Earlier this year this involvement has caught up so expect that this aim can be reached.

The government has caught up so expect that.

Amy can be against it.

At each.

Slide 22, I will move to another proof of concept study which we're doing which is some combination treatment evaluating combination therapies in patients with Nash is a very important topic.

The combination treatment.

It's how you weight in combination therapies in patients with Nash is a very important topic. So.

We have chosen to stop the study proof of concept study combining levels which is an [FGF has two inhibitors.]We believe that this is fairly attractive.

She has two inhibitors, we believe that this is a fairly attractive.

Combination of compounds for patients with Nash terminals for patients with Nash, who also have type two diabetes and that is the patient population we are studying in this proof of concept study so on slide 23, a little bit of background information as I mentioned before a large proportion of patients with type two diabetes and Nash.

Proof of concept study so on slide 23, a little bit of background.

<unk> as I mentioned before a large proportion of patients with type two diabetes and Nash.

Perhaps also other aspects of metabolic syndrome of course, often there will be not always but often to have some dyslipidemia profile.

They have hypertension, cardiovascular risk factors, and underlying that is treatment systems as a very foundational abnormality in metabolic diseases.

Foundational abnormality and metabolic diseases.

Type two diabetes is increasingly prevalent it's already very prevalent steady increasing with half a billion people affected globally.

So decrease a little bit.

Half a billion people affected globally.

And if you look at patients with type two diabetes and also has received, that's undergone a liver biopsy you actually find that's prevalent in quite a high percentage and as I mentioned before the more advanced diseases. All of this totaled more often at this point.

At this point.

Costs will be prescribed. Insulin resistance is a key part of physiological events, leading to many downstream effects inflammation et cetera, and clinical manifestations essentially of the entire metabolic syndrome including Nash and type two diabetes. There's

The clinical manifestations essentially off the entire metabolic syndrome with tooling.

Nash and type two diabetes, so there's a lot of.

Lots of good reasons to combine sort of physical pounds that address these upstream metabolic immune pathways of Nash and type two diabetes and would be beneficial for both conditions as well as the other manifestations by extension of metabolic central.

Type two diabetes and would be beneficial for both conditions as well as the yield of manifestations by extension of metabolic central.

So, that's the rationale to combine drugs that have complementary mechanisms of action to show at least additive effects.

Drugs that have complementary mechanisms of action to show at least additive effects.

The metabolic immune aspects of the disease and it is expected that these upstream beneficial effect will then take you through more downstream effects of the disease, which includes also of course fibrosis.

Upstream beneficial effect will then take you through more downstream effects of the disease, which includes also of course fibrosis.

So that would be Florida tool, which further elaborate on the rationale why [ ] and [ ] are a very attractive couple in the context of combination therapy.

<unk> and <unk> at a very attractive couple in the context of <unk>.

The combination therapy.

[ ] has really exploiting the benefits so faulty part.

Exploiting the benefits so faulty part.

Transcription factor saw a sub-debt adult plan hummer and having an effect on multiple organs as a result of combined effect on improving lipid metabolism improving tangible positive metabolism and anti-inflammatory effects.

And having.

Got it affects multiple organs.

As a result of combined effect on improving lipid metabolism roofing tangible positive metabolism.

<unk> and anti inflammatory effects.

Well defined effect on macrophages to differentiation to them, the non inflammatory phenotype et cetera.

The tier two and you'll just have a more upstream effect essentially.

The reuptake of glucose in the kidneys causes a point 17 compound to smelt sort it has itself a huge effect and of course, improves the underlying metabolic dysfunctionality of type two diabetes.

Metabolic the underlying metabolic dysfunctionality of type two diabetes.

They also have theoretic effects so they use volume and there are benefits in preventing heart failure Cadillac disease has been well defined, meanwhile, very high profile studies, specifically also at recently, Florida and positive flows.

I would I think effects so David Hughes.

Volume.

And there are benefits in preventing heart failure.

Cadillac disease has been well defined Meanwhile, very high profile studies, specifically also at recently, Florida and positive flows.

So that makes them attractive as combination compounds.

And slide 25, which explains the studies called legend is based on an acronym.

It's also I think a very good name for the study.

The name for the study.

The expected benefits of the combination of these two compounds is obviously with regard to the secrecy.

Secrecy.

And.

Uh huh.

One of them.

One of the interesting aspects that people look at in the legend study is the effect of the combination on the distribution of fat and the biology of fat because a lot of people are not has about one set of patients you see an increase in weight.

<unk>.

Legend study is the effect of the.

Combination on the distribution of fat in the biology of FX because a lot of people are not has about one set of patients you see an increase in weight.

It's important to remind the audience that the weight increase that we see with Lama similar not as different metabolic speak from the weight gain that is seen in patients or people, who don't eat healthily or don't have enough physical activity, so this weight gain is actually has been well defined with being metabolically healthy.

I'm being metabolically healthy leaf.

These patients also have felt the same improvement in insulin resistance and other markers that has also been prescribed with Promethazine, so the weekend itself is not a metabolic concern, but it can be a concern for patients. So there isn't a need to benefit.

Improvement in insulin resistance markers. What has also been described for five minutes or so so the weekend itself. It's not a metabolic codes. So that it can of course vehicles for patients. So there isn't a need to benefit.

To have an answer for those patients who have a wage increase that maybe a concern for them.

Answer to for those patients who have a wage increase that maybe have concerns for them.

And given the fact that [inaudible] two inhibitors have a weight reducing effect of a combination of the 2, in addition to showing an improved efficacy also balance out the tuition.

<unk> two inhibitors as in a way, it's reducing effect.

It's a combination of the 210 in addition to showing an improved efficacy also balance out the tuition.

The weight changes that you see with Lanifibranor.

What we will also do in the study is look at imaging using MRI.

Imaging.

MRI.

Liver multi scan, which will get us on the picture on the effect of Lanifibranor alone and the combination of Lanifibranor.

And [inaudible] on liver fat.

Liver fat.

On inflammation and fibrosis, but also on the distribution of fat in the body because.

If you if it gets.

Pete.

Specifically people how much activity there is some maturation of fatty acid to lot smart insulin sensitivity.

Yes.

The fat tissue that is more located in the subcutaneous features.

Next shown for the Lanifibranor reduction in liver fat, but this study will provide more details.

And expected to reach distribution of fat towards more metabolically healthy fat.

The primary efficacy endpoint is [inaudible] makes no sense because it's obviously the main efficacy endpoint in diabetes studies, but it's also biologically relevant linked to insulin resistance in the pathogen.

Secrecy endpoints in diabetes studies, but it's also biologics elephant linked twitch and some need assistance in that.

Of Nash and we do know about the effect of Lanifibranor of HPLC is from the naked study.

So slide 26.

The sign of the legend study.

We are in this top expense.

Excellent.

The principal investigators will be Doctors, Michelle lie and Oh, Hello, bolt from Harvard University events to them prospectively.

Doctors, Michelle lie and Oh, Hello, bolt from Harvard University events to them prospectively.

The study will be conducted on both sides of the Atlantic in the U.S. and four countries in Europe .

Four countries in Europe .

With an expected stumble of 50 sites and as Pierre had mentioned.

The diabetes division has approved the IND so the study can proceed and we are planned to start.

Accepted.

approved the IND so the study can proceed and we are.

<unk> planned to start.

So the first half of this year and we'll have top line results in the second half of next year.

The first half of this year and we'll have top line results.

In the second half of next year.

Inclusion criteria would be adult patients who have type two diabetes in Nash obviously.

And.

And it will be from a design aspect. It's of proof of a concept study. So it's an exploratory study.

The comparison between Lanifibranor and placebo will be based on a double blind assessment.

<unk>.

Combination relative to <unk>.

And publishers.

There will be an open label.

<unk> board and populous listen well.

Which is adequate for proof of concept purposes of this study. The primary efficacy endpoint is to change in HPLC and again as I mentioned before we pass it goes measure.

To calculate.

To calculate that because we know the effect of Lanifibranor from previous studies and then we'll have some broad panel of secondary efficacy outcomes.

Outcomes.

Based on imaging, so our assessment of hepatic fat inflammation Santos et cetera.

All Microsoft lipid tongue carbohydrates and metabolism markers of inflammation and then again just changes in body fat composition potentially be authentic complementary.

To the study from Dr. Cozy.

In solving that's expected in distribution towards what's more healthy, metabolically healthy subcutaneous fat.

Number of other outcomes of course,

We look at safety, adverse events, totaled ability, and body weight. I mentioned before we expect that I mean, that's a combination of lot of people in all of the answers two inhibitor.

Will be wage neutral, but has also been shown for [inaudible].

Diverse.

[inaudible] two inhibitors.

If we look at some kind of takes into study.

As I mentioned imaging. And the bottom of the slide to see the design of the studies summarized again as I have mentioned so half of treatment four weeks of follow up and after treatment.

Move to slide to see the design of the studies summarized to gain insight pension so healthy of treatment four weeks of follow up after.

Treatment.

In summary on slide 27.

There's a lot to say, I think its very promising and we also receive a lot of enthusiastic feedback from pathologist and diabetologist alike on a combination of Lanifibranor and [inaudible]

Battologize diabetologist to like on a combination of lot of people don't want to impact that Susan.

It's a pool of concept study that will provide.

Will show us again, the effects of Lanifibranor of course on the different metabolic immune aspects of Nash and type two diabetes, but also the effect of the combination with [inaudible] acting on upstream metabolic pathways.

HPLC as I mentioned is the primary efficacy endpoint. The data on body composition, I think will be very novel and important to look at.

Novel and important to look at.

We expect this distribution of body fat and to once more subcutaneous fat and then obviously since we are positioning and developing Lanifibranor for Nash.

Distribution of.

Body fat and.

While small subcutaneous fat and then obviously since we are positioning and developing a lot of people in her for Nash.

Okay.

We look at the liver and liver markers enzymes, markers of liver inflammation in pathogen fibrosis.

<unk>.

Microsoft.

Markers of liver inflammation to [inaudible] fibrosis will all be assessed through blood tests as well as imaging.

That's as well as imaging.

So with that, back to Pierre on [inaudible] gowns.

Thank you Michael.

So, let's indeed switch gears for [inaudible]. So, can we be on page 29 please.

So as you probably know the Oregon.

Once daily administered or gamma inverse agonist, which is currently investigated.

The phase 2b clinical trial for the treatment of moderate to severe [inaudible] and this decision came out from a successful phase 1B study.

Our successful.

<unk> B study.

In patients with moderate to severe failure [inaudible] .

[inaudible] was discovered jointly by Inventiva and AbbVie.

And [inaudible] royalties really have the potential to be an important source of revenues for Inventiva.

Indeed, if you consider the success of anti-IL17.

Or anti-IL23 biologics in the treatment of [inaudible].

Which is validating IL-23 IL-17 pathway.

<unk> 2017 pathway.

As an important target for therapy, then you may see that there is quite a significant market opportunity for [inaudible] and efficacious treatment acting on[inaudible] in cirrhosis, but there is also a potential market opportunity for this approach in other immunology indications, where IL-17 is relevant.

In cirrhosis, but there is also a potential market opportunity for this approach in other immunology indications, where IL17 is relevant.

Next slide please.

So why is the IL23, IL17 pathways so relevant? [inaudible].

And 23 seven.

17 pathways, so relevant infill yet.

Actually, one of the primary drivers of the inflammatory response in [inaudible].

Is IL17, which is secreted from TH17 cells.

And 17 regulates the proliferation of [inaudible].

And down regulate their differentiation.

It also uses [inaudible] to secrete chemicals that drive the influx of immune cells, including neutrophils and [inaudible] cells.

Nice to see creep Kim with guidance.

That drive the influx of immune cells, including neutrophils.

And then with <unk> sales.

[inaudible] is a nuclear receptor, which controls IL17 cell differentiation and effector function.

And effector function.

[inaudible]18, the transcription of IL17A and IL17S.

Ias 17.

And blocking of all gamma, actually prevents TH17 differentiation.

And inhibits IL17 production.

70 production.

Next slide please.

And this is actually illustrated in one of our publication exemplified here.

One of our publication exemplified here.

So for example, if we consider a 97/58, which is one of the early oral [inaudible] gamma inverse agonists that we discovered with AbbVie.

$97 58, which is one of the early <unk>.

Uh huh.

That we discovered with Abbvie.

Reported in this paper that in vivo, in the model of [inaudible] in use by anti-IL23.

The model of <unk> is used by 23.

Which is actually an interesting model because we see there, time-dependent accumulation of [inaudible] expressing cells across both the dermis and the epidermis.

Time-dependent accumulation of [inaudible] expressing cells across both the dermis and the epidermis.

Across both the dermis and the epidermis.

Epidermis.

In this model, A95/78 was effective in reducing inflammation driven by IL23 and attenuated AP they'll move thickening.

$95 78 was effective in reducing inflammation driven by 'twenty three.

And attenuated AP they'll move thickening.

A95/78 was also effective in suppressing the gene signature associated with IL23 exposure including a significant decrease in IL17A and IL17F gene expression.

Associated with page 23 exposure.

Including a significant decrease in IL 17, eight <unk>.

<unk> F gene expression.

And the treatment with A95/78 also reduced the number of [inaudible] that were reduced by IL23.

<unk>.

Were used by 'twenty three.

And this was seen both prophylactic and therapeutic administration.

Therapeutic administration actually led to an 85% reduction of IL23 then Skinner's formation and reduced IL17A as well as IL17F gene expression and protein levels.

Three two then Skinner formation and.

And reduced <unk> eight as well as <unk>.

Ft expression and protein levels.

In addition to that, we know that clinical studies have shown that biologics against IL23 has been ineffective against [inaudible] parties.

We know that clinical studies have shown that biologics against relatively.

<unk> be ineffective against who met.

While those targeting IL17 show promises.

And here in the middle of rheumatoid arthritis.

A95/78, was capable of reducing push swelling by 41% to 84% depending on the timing of administration, which compares favorably to [inaudible] therapy.

Which compare favorably.

TNF therapy soon this.

This is actually a good proof of concept for the whole year available gamma inverse agonist in all these different preclinical models.

Next slide please.

So indeed substantial commercial opportunity exists in [inaudible] for an overall an efficacious treatment.

As you all know this is a common skin condition that affects 2% to 4% of the population in western countries with global sales in 2020 of approximately $20 billion.

Approximately $20 billion.

The market today is dominated by injectable, anti IL23, IL17, TNF Alpha biologics, which account for more than 80% of the market.

I 17, TNF Alpha biologics, which account for more than 80% of the market.

However, a Tesla a novel drug [inaudible] four inhibitor.

despite failure of efficacy and tolerability profile compared to approved injectables, generated. $2.2 billion of sale and was acquired by [inaudible] for $13.4 billion in 2019.

Tolerability profile compared to approved Injectables.

Generated.

$2 $2 billion of sale.

And it was acquired by <unk> for $13 4 billion in 2000.

19 of them.

So, there are also a number of other [inaudible] available candidates that has been investigated as potential therapeutics for the treatment of [inaudible].

Been investigated potential therapeutics for the treatment of <unk>.

Clinical results from our phase III clinical trials found that [inaudible] inhibitors were able to reduce and creating 75 responses that approach biologic-like therapeutic benefit.

Janus kinase.

<unk> inhibitors were able to reduce and creating 75 responses that approach.

Biologic like therapeutic benefit.

However, the high efficacy seen with some drugs of this class was associated with increased risk of adverse events, resulting in discontinuation of development for this indication.

There is a current clinical development focus on inhibitors of dealers in China is too big too.

These are distantly related tech family member.

[inaudible] recently reported that [inaudible] two inhibitor do cover [inaudible] achieved [inaudible] 75 response in about 50% of patients by week 16.

And about 50% of patients by week 16 them.

Next slide please.

[inaudible]

[inaudible] phase two b trial in adults with moderate to severe [inaudible] with an estimated time completion date of March 23.

In microsurgery news, the Vice Chairman and President noted that city, Oregon showed promising activity in the previous phase would be patients with clinic [inaudible].

So next slide if we look at the design of the Phase 2B study, we just started, it's a double-blind placebo-controlled trial evaluating the safety and efficacy of three doses of the [inaudible] in 200 patients with moderate to severe [inaudible].

The design of the Phase <unk> study, we just started.

It's a double blind placebo controlled trial.

Evaluating the safety and efficacy of three doses of the [inaudible] in 200 patients with moderate to severe [inaudible].

And the primary outcome is the percentage of participants achieving at least 75% reduction from baseline in [inaudible] score.

I mentioned the results of this study would be available in the first semester 2023.

Yeah.

So next slide please if we look at the [inaudible] landscape, we actually believe that this competitive landscape today is limited with 3 compounds, including city, Oregon in the phase 2.

Yeah my competitive landscape.

We actually believe that.

This competitive landscape today is limited.

With a C.

C compounds, including city, Oregon.

In the phase III.

[inaudible] from BI, which status is not clear considering that it is not mentioned anymore in the annual report.

Annual report.

Our [inaudible] product AUR101, which is a BID product, starting a phase II in the US as we speak.

You are 101.

She is a b I D.

Product, starting a phase II in the U S as we speak.

GTE 451 out of [inaudible] tobacco, which has actually limited efficacy results from the study is actually available on clintrial.gov, showing that at the top dose GTE 451 was a goal to achieve passage 75 in 22% of patients.

It's up in tobacco, which has actually limited efficacy.

Results from the study is actually available on clintrial.gov, showing that at the top dose GTE 451.

They both to achieve passage.

<unk> 75 in 22% of patients.

And this after 16 weeks of treatment.

And finally, the unique product IMU935.

With phase 1B ongoing exploring the efficacy of [inaudible] 50 milligram QD and BID in patients with moderate to severe [inaudible] and this due in 28 days.

And this due in 28 days.

Two.

These.

Next slide please.

So I've mentioned the device eligible to receive development regulatory commercial milestones and Tier royalties and these royalties range from the mid-single to low double digits.

<unk> device energy.

Boom to receive development regulatory.

Commercial milestones.

Tier royalties and these royalties ranging from the mid single to low double digits.

It actually a therapeutic space, where you can see that competitors have all reached blockbuster status.

Competitors.

All right.

Blockbuster status.

I know collectively to the limit of [inaudible] for the patent.

CVT four the patent.

But that's been filed in 2016 studied up to 2036 and [inaudible] 5 year extension period.

Five years extension period.

We have a limit of exclusivity of 2041.

2041.

And with that, I would like to give the floor to [inaudible] for the financial results.

<unk> the floor.

For the financial results.

Yeah.

Yes, good afternoon, good morning.

We view the financial performance in two slides.

First of all the big picture of the shareholder base, which is stable.

And I've even been consolidated thanks to the ATM of 32 million US dollars.

So embarking existing shareholders plus opening newcomers in the shown debate.

<unk> shown debate.

So the market cap is at $450 million.

At $450 million.

The performance in the market was quite positive in 2021, although.

The business sector and biotech in particular.

We are suffering from the Ukrainian crisis.

In terms of cash that's quite easy to remember this because we are close to $100 million.

If we take into consideration the 4 million euros milestones received in January from Abbvie, and our estimate for the cash runway is 1 year from now.

Yours milestones received in January from Abbvie, and our estimate for the cash runway is.

One year from now.

Next slide thanks.

So the figures are quite easy to read they are in the continuity of which we had discussed for the H1 financial performance.

We had discussed for the H one.

Our financial performance.

The revenues are made up of the milestone from [inaudible] $4.2 million.

The key information for is the R&D expense, which has doubled in '21 when compared to 2020 with 48.5 million.

The R&D expense expense, which has doubled.

In 'twenty when compared to 2020 with 48 four.

<unk> 5 million.

G&A of course is definitely related to what has been explained in the activity of clinical development and on our assets in particular on 90 [inaudible]. The G&A as expected decreased by 31%. It was fully expected [inaudible]

The clinical development.

Our.

In particular on 90, if you run all the G&A as expected.

<unk> decreased by <unk>, one percentage was fully.

Expected first here.

For <unk>.

Compete here with the dual listing status.

The dual listing status.

No surprises [inaudible] under control.

Beyond our control.

Cashwise as I said, were close to 100 exactly $95.4 million on top of which we can confirm that the 4 million received in January.

They said, we're close to 100 exactly $95 4 million.

Top of which we can we can confirm that the 4 million received in January so I guess as.

As I said one year of cash to operate and the way it has been built is in line with the operational expense.

Cash to operate and the way it has been built.

In line with.

Operational expense.

The net of our in-cash flow used in '21 reached close to $50 million.

In 'twenty one reached.

Reached close to $50 million.

Compared to $13 million last year and in terms of cash investing activity and financing activity has been offset by the ATM that took place end of September raising gross proceeds of $32 million as we said.

September .

Racing.

Gross proceeds of $32 million as we said.

So the cash flow is comfortable for the next 12 months in our sector.

Comfortable for the next 12 months.

Our sector.

Industry. So of course, I would be happy to answer any further information if you need more colors on the financials. Thank you.

Further information if you need if you need more colors on the financials. Thank you.

And then the last slide before we move to the Q&A are the anticipated key milestones and focus only on the clinical readouts that we start with landed here we live.

Q&A.

Anticipated key milestones and focus.

Only on the clinical Readouts that we have.

Start with landed here we live.

The second half the clinical results the topline results of the study with patients with type two diabetes a study conducted by Dr. Cozy.

Early '23 we live [inaudible] end of the 15B.

The <unk>.

Of course once again the publication of these results like the publication of phase 1B [inaudible].

The publication of the phase when the R&D and all that.

Then.

[inaudible] always in 23, another important clinical readout that the combo study land [inaudible].

Of course, I'd say the very important top-line result in the second half of '24 of the native III phase III.

I'd say the very important top line result in the second half of 'twenty four.

Native <unk> III phase III.

So that's for the [inaudible] and then it will be powerful as I mentioned in my introduction, we continue to work to prepare a meeting with the FDA.

Validated clinical development plan, the pivotal trial, and hopefully is an important piece of information for identifying a renewal for [inaudible].

Renewal for Woodsy Park.

So these are the key milestone, but this concludes the highlight of 2021, and we will be ready to take questions and the operator will give you the detailed procedure to follow.

The highlight of 2021, and we will be ready to take question.

The operator will give you the detail.

Procedure to funnel.

Thank you if you would like to ask a question, please press star one on your keypad and wait for your name to be announced if you'd like to cancel that request, you can press the hash key.

That's star and one on your keypad, if you have a question today.

Your first question is from the line of Lucy Codrington from Jefferies. Please go ahead.

Hi, there and thanks for taking my questions.

Yes.

Firstly, on the cash runway can I confirm does that include the costs of the legend trial? and I'm assuming doesn't include any other potential [inaudible] from apathy why do you think from all the powerful.

and I'm assuming doesn't include any other potential [inaudible] from apathy why do you think from all the powerful.

And secondly, and apologies if I missed it, and regarding the phase III with treatment is that progressing as planned?

And I noticed on the slides that it looked like Russia and Ukraine account for about 22 sites, which is about half of the EU sites currently active. How many of those 22 sites were active and what drives confidence that there isn't the need for the delay in the data?

Russia, and Ukraine account for about 22 sites, which is about half of the EU sites currently active how many of those sites.

Yes.

And what drives confidence that there isn't the need for the delay in the data.

And then just finally on the milestones remaining from apathy, I believe it's $35 million and we've had two, so am I right in thinking there are $27.5 million euros left?

I believe that you felt like.

And we've had he.

Thank you Mr. <unk> seven 5 million.

Thank you.

Thank you Lindsey.

For the cash runway, maybe Joe you want to.

Your question about the budget definitely taking into consideration this additional study, it's clear.

Taking into consideration. This addition.

Steady clear.

Considering the masters and [inaudible] there is no milestones planned in '22, according to the development plan.

In 2002, according to the development plan.

We may hope that in '23 if there are good news, we could have an additional item outside the contract.

The contract.

The second question.

The remaining milestone from Abbvie.

No.

So we can get back to you.

We can come back.

It would be finding in the filing in the URD. in the 20th that would be fine [inaudible] next Friday.

In the in the filing in the U R. D. In the 20th that would be fine.

Next Friday.

If it's not written down in this document, I think if it's documented we you can provide.

It is documented we you can provide.

Once again, what is important of course, this milestone with nice to receive but which really make the value of this contract are the royalties, which are we view them as very meaningful and the double-digit level is triggered at the sales level to where I am personally very confident this program will reach.

is triggered at the sales level to where I am personally very confident this program.

We'll reach that.

To your question about the Ukrainian and Russian site.

We were planning to open 10 sites in Ukraine, Ukraine is one of the 11 countries that are currently open.

And we had 3 sites that started screening patients.

That started.

Treating patients.

The other seven were not open and as you can imagine, these 10 sites all activities have been posed given the situation, I would say that we have very limited activity will review there. The other 12 sites are Russia. Russia is not a country that is opened yet.

I would imagine.

10 sites all activities have been posed.

Given the situation I would say that we have very limited.

Activity will review their the other website.

Russia, Russia is not a country that is opened yet.

The regulatory filing [inaudible]

Joey.

No impact I would say on the current the screening activity.

And overall, we have 22 sites that we need to recover so if you look at the various presentation you will note that we have increased the number of target sites, we now targeting 350 on both.

We have 22 sites that we need to recover so if you look at the various presentation you will note that.

<unk> increased the number of target sites, we now targeting 350.

Both.

I think when we started prior looking at 250 and we have increased that.

For example, as Peter mentioned, we recently contracted with summit which is specialized in recruitment Nash very efficient organization. Which sides, mostly in the US, particularly in Europe, and so that also will contribute to reduce the impact of the situation.

Specialized.

In.

Recruitment Nash very efficient organization.

Which side, mostly in the U S, particularly in Europe , and so that also will contribute.

Two.

To reduce the impact of.

The situation.

Of course, in addition to that, working with [inaudible] to see if we can find a different insight.

That working.

Working with icon to see if we can find.

Different site.

Yeah.

Thanks very much.

Thank you. The next question is from the line of Joanne Vandenbosch from KBC Securities. Please go ahead.

Yes, thank you and congratulations on yet another great year.

Definitely.

You bet.

Building on maybe the question from Michael Funk.

Really quick first question.

Looking at [inaudible], the data today as it stands is that based only on existing data?

The data today.

As it stands.

Is that.

Right.

Hum.

Existing data.

Yes.

Or is there currently also other information that you've been using of preclinical data to build the legend trial?

Formation that you've been doing.

Preclinical data.

To build the legend trial.

And then going further, how are you looking at the future of Lani and [inaudible]? Are you still open to potential other collaboration building the market together with our other organizations, or are you really focusing on bringing it to market yourself?

Maybe.

However.

How are you looking at the future of Lani and had never been done already powerful argue.

Still open to potential other collaboration building.

The market together with our other organization or are you really focusing on bringing it to market yourself.

Okay. Thank you for our rationale data available as noise Pierre or Michael do you want to take this question?

Our rationale.

Data available as noise or Michael do you want to take this question.

Yeah.

I think we can refer to Michael because the [inaudible] is very much coming out of a number of clinical trials we're in our other [inaudible] two inhibitors were given on top of patients being treated by Pioglitazone for example.

A number of clinical trials.

We're in <unk>.

Our other <unk> two inhibitors were given on top of patients being treated by Pioglitazone for example.

You would see there a decrease in body weight.

The decrease in body weight.

So I don't know Michael if you want to elaborate on that.

Well.

This just summarizes it's both yes.

<unk>.

The mechanism of action of these compounds will spend [inaudible]

That's it.

People are going to extend its truthful and public funds.

[inaudible]

And the efiicacy in humans is also well known.

[inaudible] has been approved for awhile [inaudible]

And the data from patients and diabetes and cardiology.

And cardiology.

So.

That provides a strong rationale for the combination. So we do not need for this purpose non clinical data.

A strong rationale for the combination of lines. So we do not need for this purpose non clinical data.

So if I understand it correctly Eric in your view enough, let's say circumstantial data through which you don't expect any [inaudible] of the use of the drug.

Eric in your view enough, let's say.

Circumstantial data through which you don't expect any.

Emanation of the use of the drug.

Correct. [inaudibe] is approved anyway.

In particular <unk> is approved anyway.

So.

In patients with metabolic immune diseases, which includes.

Metabolic immune diseases, which includes.

[inaudible]

These patients have multiple drugs in combination is automatically the case.

Many patients have tetnus for example.

So there's nothing unusual combination.

We are actually studying it for the purposes that I explained to show that such a combination can have additional benefits on the efficacy readouts for Nash and type two diabetes and weight management plans for those patients who may need it but there is no need to look at the support ticket Jewish non-clinical data in order to have a strong rational specifically, for

As you can see Readouts for Nash.

Nash and type two diabetes and.

Weight management plans for those patients who may need it but there is no need to.

You look at <unk>.

Support ticket Jewish North clinical data in order to have a strong rational specifically, Florida.

[inaudible]

There have been large studies published that have been conducted in basically every globally combining [inaudible] all four major.

<unk> conducted in basically every globally.

Combining.

It's probably too soon with all four major.

Yes, just two splits on the market and the findings were fairly consistent.

[inaudible]

Sorry.

And in these indications would it be the ultimate idea to market them by yourself or in combination with other partners or how do you see that going forward?

[inaudible]

Patrick, you want to continue?

[inaudible] to answer the second part of your question Phil.

The second part of your question Phil.

[inaudible] we view it as a tremendous opportunity for big pharma now she's certainly a very large market, but you need the muscle, experience, the commercial capabilities of a big pharma. Our objective is to find a partner we believe that the asset is a great value great chance to make it to the finish line.

The tremendous opportunity for big pharma now she's certainly a very large market, but you need the muscle.

experience, the commercial capabilities of a big pharma. Our objective is to find a partner we believe that the asset is great value great chance to make it to the finish line.

And we are open to find a partner most likely it will be in a better position once we have the phase III data, but of course, if somebody knocks on the door before we are certainly open to discuss.

It will be in a better position once we have the phase III data, but of course, if somebody knocks on the door before we are certainly open to discuss.

For the other product.

Sure.

The easy one is [inaudible] again. So everything is in the end of AbbVie.

They decided to start developing for IC they can decide to look at the other indication, but that's clearly on their end, and they are in charge of fully funding the development as well as the commercial redistribution.

And then the last one, it will be powerful there. We have not changed our strategy. We do not have the capabilities to develop LANI and NASH energy power and NPS 6 in parallel, but we remain committed to find the new opportunity because we believe the patient with NPS 6 deserves a new treatment energy path so it could be this new oral treatment that they are looking.

We do not have the capabilities to develop Nash <unk> Nash and of the powerful and NPS six in parallel, but we remain committed to find.

<unk> because we believe.

The patient with NPS.

<unk> two of a new treatment.

The powerful could be this new wood treatment that they are they are looking.

Thank you.

Thank you. The next question is from the line of Sean [inaudible] from Bryan Garnier. Please go ahead.

Okay.

Yes, good afternoon, and congrats again for the very strong year.

There is a stronger year.

Three questions, if I may. The first one is...

Hello? Can you hear me?

Yes, yes, perfectly.

Hello?

Yes, we can hear you.

Can you hear me?

Yes.

Okay, so sorry, sorry.

So.

Okay, great.

First, on the legend trial, could you remind us why you have chosen the 9800 milligram in note 1200?

I think the 800 milligram was not the best during the native trial, especially regarding efficacy.

During native try ordered and especially regarding efficacy.

The second question is [inaudible] you are quite busy with LANI, but could we have an update on the [inaudible] for example, program or do you have all of the products in the pipeline, which may move forward in the next few months, for example, of this year, from which we may have some some news even easy all preclinical or early stage?

Related that you all are quite busy with Lenny. Now that. We have an update on <unk> for example, a program or do you have all of the products in the pipeline. Which may move forward in the next few months. For example, with this year. From which we may have some some news even easy all preclinical or early stage.

Now that. We have an update on <unk> for example, a program or do you have all of the products in the pipeline. Which may move forward in the next few months. For example, with this year. From which we may have some some news even easy all preclinical or early stage.

We have an update on <unk> for example, a program or do you have all of the products in the pipeline. Which may move forward in the next few months. For example, with this year. From which we may have some some news even easy all preclinical or early stage.

Which may move forward in the next few months. For example, with this year. From which we may have some some news even easy all preclinical or early stage.

For example, with this year. From which we may have some some news even easy all preclinical or early stage.

From which we may have some some news even easy all preclinical or early stage.

The last one is back to the envelope calculation is that. Seems you have a cash runway until one year that means you are expected to spend about 100 million this year. So what are the main drivers and significant increase compared to last year?

Yeah. Back to the envelope calculation is that. You have a cash runway until. For one year that means you. <unk> expected. Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

Back to the envelope calculation is that. You have a cash runway until. For one year that means you. <unk> expected. Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

You have a cash runway until. For one year that means you. <unk> expected. Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

For one year that means you. <unk> expected. Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

<unk> expected. Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

Spent about 100 million this year. So what are the main drivers. And if you can't increase compared to last year.

So what are the main drivers. And if you can't increase compared to last year.

And if you can't increase compared to last year.

Think they need the phase III [inaudible], the addition of Legion what are the key drivers now?

Key.

Key drivers now.

Thank you.

Okay. Thank you.

Michael, you can take the legend. Kara can go over [inaudible] and John will talk about the cash.

Go over GAAP.

John will talk about the cash.

Okay.

We've just left Michael's line from the call, we just got to try and reconnect him.

Okay very good so maybe Pierre can you cover, yeah?

Yeah, sure I think I can cover partly [inaudible] Also, the choice was basically made on the fact that as you heard from Michael the primary endpoint is HBA1C [inaudible] is actually those that are producing already. Maximal efficacy on HBA1C there is no difference between 800 and 1200 milligram.

The choice will be.

<unk> made.

On the fact that the.

As you as you heard from Michael the primary endpoint is <unk>.

Is actually those that are producing already.

Maximal efficacy on <unk> there is no difference between the 812 milligram.

And then this is I think the major reason why this was chosen in this study, but Michael can elaborate maybe more once he has reconnected.

Reason why this is.

With <unk> in this study, but Michael can elaborate maybe more once he has to be connected.

Okay.

Do you want to comment Michael?

Yeah.

We connected briefly about.

Yeah.

It's true that if you look at our histology.

Fibrosis qualification of histology of staging of specifically 1200 milligram is better than 800 milligram after six months, which is actually a very short time frame to evaluate to fibrosis, but many other markets.

The two doses that actually pretty equally important with regard to efficacy specifically on metabolic markers and since fibrosis.

is driven by the metabolic abnormalities and inflammation is this actually an expectation that if you treat longer both doses may be compatible we don't know that, of course, made history will tell us that but that's also a main reason why we kept two doses in native III and why we chose 800 milligram in Legend, because that study we don't look at the Fibrosis so logically we look at mainly at metabolic immune markers and we expect and then an additive effect from the combination therapy.

They chose 800 milligram in.

Legend, because that study we don't look at the.

So logically we look at mainly at metabolic immune markers and we expect and then an additive effect from the combination therapy. So the east.

These are the main reasons why we chose the 800 milligram for legend.

And for [inaudible] So we have identified lead compounds couple of lead compounds that we are now progressing in vivo and in models of [inaudible] cancer and renal cancer, why because we have seen quite interesting and potent anti-proliferative effects in-vitro in a number of renal cancer cell lines and a couple of HCC or liver cancer cell lines plus.

In vivo in models of.

But at cancer and renal cancer, why because we have seen a quite interesting.

And potent anti-proliferative effects invitro in a number of renal cancer cell lines and a couple of <unk>.

HCC.

Or liver cancer cell lines plus.

These are products that are quite well distributed to the liver and the kidney.

Quite well.

Distributed through to deliver in the kidney.

So we are now starting to profile those compounds in animal models of hepatic cancer HCC and in renal cancer.

Hepatic cancer.

Cancer HCC in renal cancer.

And we'll keep you posted on that.

And the last question of the cash.

No, I think everything is mostly driven by native yes, definitely you know we finished 2020 with the slow H2 after the results of phase two so in '21, the increase is 80%, 90% due to native.

the increase is 80%, 90% due to native <unk>.

The preparation and much of this study and we met with treatment because the hero and [inaudible] in '21 and we also consolidated the development in pharmacovigilance regulatory team.

much of this study and we met with treatment because the hero and [inaudible] in '21 and we also consolidated the development in pharma.

Pharmacovigilance regulatory team.

Too faced.

The phase III and the trend for 22 would be in this direction.

We've been in this direction.

Yes.

To get [inaudible] for the phase III expense this year.

<unk> yeah.

For the phase III expense this year.

Expense.

This year.

Yes, so driven essentially by native.

Okay.

Yes.

[inaudible]

Okay, if I may just.

If I may just, a quick.

Okay.

Yeah.

I don't know.

If you did what you.

You will need to have a new phones when you're financing during prohibition.

Do you have any idea right now of what could be how are you and being such a raise? Would it be diabetes on diabetes and so on?

Okay.

Such a raise.

Would it be diabetes on diabetes.

And so on.

And I think all the options are on the table.

Non dilutive with potentially business development activity on our pipeline.

With.

Potentially business development activity on our pipeline.

Especially in non strategic areas like like Asia.

We are also looking at loan royalty deal.

Of course as mentioned, we also have an ATM in place.

So we see the right moment, what is the best option for for the company to move forward.

Okay, great. Thank you.

Thank you. The next question is from the line of Seamus Fernandez from Guggenheim Securities. Please go ahead.

Hi, This is Evan Wang on for Seamus just a question on the Aurora Gamma program can you talk more about the profile observed in phase one and how that gives confidence heading into phase 2B, especially for a competitive program product profile, I guess relative to other upcoming oral for psoriasis.

Especially for a competitive program.

Profile, I guess relative to other upcoming oral <unk> for psoriasis.

And I know you can't give that many specifics on future indications, but you know what other indications may be most appropriate for this kind of target?.

Thanks.

Yes.

[inaudible], try to answer that?

Well I think the phase one B data are not public so.

They are going to do well.

Might be that he will.

[inaudible]

The data on the phase 1B in the dedicated conference, but these data are not available.

In the dedicated confronts.

But these data are not available.

I think as he made the decision to enter into phase 2B which as you've seen is quite an important study with 200 patients 16 weeks based on data that we're convincing so I trust very much on the decision of [inaudible] moving forward with [inaudible]

We made the decision to enter into phase b piece to be.

which as you've seen is quite an important study with 200 patients 16 weeks.

based on data that we're convincing so I trust very much on the decision of [inaudible] moving forward with [inaudible]

We're convincing so.

Trust remains very much on the on the decision.

Moving forward with.

He said it will go up.

And.

So we'll see if the data would be published this year.

Relatively to your question about additional indications.

Additional indications, where we're well basically.

There are several indications where we know I17 inhibition is relevant.

You mean, those indications where we know.

17 inhibition is relevant.

Maybe [inaudible] know them. This is basically the axial spondylarthritis on [inaudible]

We know them. This is basically the axial spondylarthritis on Qdoba.

So you take arthritis in [inaudible] got to the heart.

In particular <unk> got to the heart.

Based on the data we have obtained with this early [inaudible] second is we could discovered with Abbvie on the intermodal rheumatoid arthritis, where we see quite the significant reduction of pull inflammation could be [inaudible] also makes sense for such molecule and renewal through that [inaudible] potential additional indication for this type of mechanism of action.

<unk>.

This early.

The second is we could discovered with with Abbvie on the <unk>.

Intermodal rheumatoid arthritis, where we see quite.

The significant reduction of pull inflammation could be.

<unk> also makes sense for such.

Molecule.

Renewal through that discrete itc's potential additional indication for this type of <unk>.

It's both actually.

Okay.

Yeah.

Thank you.

Just a reminder, if there are questions today, you can press star and one on your keypad.

And the next is from the line of [inaudible] from Societe Generale. Please go ahead.

Yes, Thank you and good afternoon good morning everybody.

And just to be back on the right of way regarding the cash position for '22 and '23.

Unfortunately for 24.

I don't see any reason so far to have a massive cuts into the R&D in '23 '24.

To have a massive cuts.

Cuts into the R&D in 'twenty three 'twenty four.

Meaning that more or less '22 number could be extrapolated for the following you have Shawn can you confirm that to me? Please?

More or less 22.

That number could be extrapolated for the following you have Shawn can you can you confirm that to me. Please.

Secondly.

Thank you a question for you.

Regarding the situation in eastern Europe .

When I made the calculation more or less 446% of that.

The patient for that for the <unk> trial will be.

We'll be impacted.

Sure.

Do you can you.

Thank you yourself short Chris please.

Gardening.

The last patient first visit timelines.

How do you see the the completion of the trial so far.

Despite the fact you get.

No there.

Alright.

Cherilyn, both BMO and bought them.

How are you optimistic or do you think we are.

We have to.

Do you see some delay going for what.

And how would that impact between the European population in the U S.

The other type of population can you make in Europe there are some.

Right.

Rick reaching more patients to get the same patient population.

Good afternoon, Dave can I take the first question.

We're right about the range of expense that we may incur in 'twenty three according to our best estimate.

<unk> and 'twenty three are in the same manner.

Same amplitude as for 2022 .

Okay.

On the question about <unk>.

What is the impact.

Of Ukraine, and Russia situation on the trial.

So we don't see that.

This is <unk>.

The overall recruitment of the triumph, we stick to the.

Two.

The guidelines, we provided which is to finalize recruitment.

This year.

Of course, we need to find.

Monitor monitor the situation.

Also find other auction in a certain sense. We had also anticipated or we had also will increase the overall number of sites was again.

We are now 350 sites on target is above what we had.

As planned at the beginning.

And so we are looking with icon at alternative.

First is to find in the country that are open.

Hi.

The capabilities too.

Recruit efficiently the patient for the part one.

And then the second option is to go into new concrete but of course, if we do that.

It would be.

Given the regulatory timelines.

That could come in most likely for the park to rather than the part one.

Okay. Thank you.

Otherwise we had a question on the VA.

Via Internet and I think we've covered most of them most of them.

The only one we did not cover will be where the question. If we believe we can do a partnership before or after the data.

Of course, given the and.

Input on that.

What we can say that we believe Nash is a playground for big pharma, we are open to do a partnership.

Terms are good we can do it in the short term otherwise it will have to be both to phase III.

Okay.

And we don't have any other questions over the phones at the moment.

Okay.

I think it's amendment to conclude thank you very much for attending and the good level of question and discussion.

Next event for Us in June .

In person growth very much looking forward to do that.

As you can imagine with submitted.

The new data abstract.

They will get accepted and we will organize.

And of the Kols webcast to go over.

The Nash space the key data presented and also the new data that we that will be presented at Eagle in the June in London, and so I really hope to see all of you.

In London in June Thank you very much and have a great day.

Thank you. This does conclude the conference for today. Thank you for participating you may now disconnect.

Okay.

[music].

Okay.

[music].

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