Half Year 2023 Genfit SA Earnings Call
Good day and welcome to the Gen Fit conference call. Today's call is being recorded.
At this time, I would like to turn the conference over to Stephanie Magner. Please go ahead. Hello everyone. Thank you for joining us on our 2023 Half Year Earnings Call and Corporate Update. Following publication of our half year results press release.
Brush release can be accessed via our website at ir.genfit.com in the news tab.
Joining me on this call today are Pascal Prejean, CEO and members of the management team.
Before we begin, I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to GenFIT's expected future performance, business prospects.
events or plans, including ability to meet and obtain milestones through our licensing agreements, obtain regulatory approvals, anticipated timelines for clinical development, study enrollment, and data release dates.
well as expected cash used in our operational activities and cash runway are forward-looking statements as defined under the US private securities litigation reform act of 1995.
They're based on our management's current assumptions and estimates, which although believed to be reasonable, are subject to numerous known and unknown risks and uncertainties, which would cause actual results to differ materially from those expressed in or implied or projected by the forward-looking statement.
For further discussion of the material risks and other important factors that could affect our business operations and financial results, please refer to those contained in our most recent filings with the SEC and AMF. These forward-looking statements speak only at the date of this webcast.
Other than is required by applicable law, the company does not undertake any obligation to update or revise any forward-looking information or statements, whether as a result of new information, future events, or otherwise.
Following the prepared remarks, we'll open the call up for questions that will be addressed by GenFIT management. Please limit yourself to one initial question to allow time for others.
I now turn the call over to our CEO Pascal Prigent.
Thank you, Stephanie.
Well, this is an exciting time for GenFit as we are now entering a new era for the company.
Indeed, we are now pivoting from a model that was centered on El Efibarno to one where we will be focusing on the development of a promising portfolio of direct candidates targeting primarily ACLS.
Elafybana was discovered at GenFit and the company took it all the way from drug discovery to phase 3.
These years of development culminated earlier this year when, at the end of June , we announced positive data from a 52-week double-blind treatment period of a pivotal relative phase free trial of el-Asibano in PBC.
As a reminder, the trial met its primary endpoint with a statistically significant higher percentage of patients achieving a clinically meaningful colostasis response compared to placebo.
Indeed, 51% of patients on elafibonor 80 milligram achieved a cholestasis response compared with 4% on placebo. It means that we saw a strong treatment effect with approximately 13 times more responders on the active arm compared to placebo.
We hit the first key secondary endpoint, normalization of ALP at week 52, which was also highly statistically significant.
Although the other key secondary endpoint did not reach statistical significance, we observed the trend for proritis improvement.
The study showed that the Tefibronor was generally well tolerated with a safety profile consistent with that observed in previously reported studies.
We believe these findings already demonstrate that elafibranol can be a very valuable option for patients with PBC.
We have seen some analysis speculating about the competitiveness of Elafibano relative to other alternatives in development.
But we believe it is an exercise of limited value at this stage.
Comparing partial high-level results across different studies without a full understanding of potential design differences or population differences is not scientifically sound.
Much more meaningful conclusions might be possible after more data is released at upcoming scientific conferences.
As far as GenFit is concerned, we are now finalizing the transfer of the Elafybano program to IBSEN that is now fully responsible for the next steps including scientific communication, regulatory filing, commercialization, and potential additional development.
We are very pleased by IFSAN's continued commitment to the program. We believe that their strong commercial track record and international footprint will enable them to make the most of the opportunity and achieve significant commercial success.
As ELA Fibonacci becomes a NPSAM program, it essentially turns into a potential source of revenue for Gen Often.
As per our agreement with Ibsen, we are eligible for up to 360 million euros of milestone payments and the first payment could start as early as later this year.
Of course, the potential approval and successful launch would trigger additional milestones and a regular stream of revenues through the royalties.
As I was alluding to earlier in this call, we are now shifting our strategic focus from a single program to a diversified portfolio of programs.
The development of Elafibano brought us two things. First, over the years, we built R&D knowledge, capabilities, networks, and strong partnerships in the field of liver disease.
Second, the successful PBC program and subsequent partnership with IBSEN brought us the funding to build and now to develop a diversified pipeline that we have strategically put together over the last 18 months.
GenFIT's focus now fully turns to our expanded pipeline in rare and severe liver diseases with a high unmet medical need with a primary focus on ACLF syndrome, also known as acute and chronic liver failure, where we are running multiple programs with several key inflection milestones to look forward to.
Our ACLF franchise now comprises five assets, all based on differentiated mechanisms of the world's action leveraging complementary pathways through different modes of administration.
So we have VSO1, NTZ,
as well the newly in-licensed SRT15 that we licensed from Ciroc Therapeutics in Seattle and CLM022 that we licensed from Ciroc in Cleveland.
well as VS02 in hepatic and sulfalopathy which is a condition
Development stages of these different programs range from preclinical to phase 2.
So let's start with the SO1, our potential first-in-class liposomal based therapeutic. It's currently being evaluated in the International UNVEIL IT Phase 2 open label randomized controlled multi-center.
proof of concept study to assess its efficacy, safety and tolerability.
addition to standard of care compared to standard of care alone in adult patients with ACLF grade 1 and 2 with a thiitis.
The first patient was randomized in early July , and we expect interim data to be available in the first half of 2024.
Given the high unmet need in this indication and the orphan drug designation obtained from the US FDA for the SO1, it is expected that the program may qualify for some of the expedited regulatory pathways provided by health authorities.
In May 2023, we presented positive data at the Digestive Disease Week 2023 from an NTZ phase one study demonstrating that it was generally well-terrrated with a favorable safety profile in subjects with moderate and severe hepatic impairment.
Preliminary data from a similar phase 1 study conducted in subjects with renal impairment also support a favourable safety and sorority profile.
So those studies enable us to move forward. But for ADTZ in ACLF, GenFIT has decided to pursue the development of a new nitazoxanide formulation, which will permit greater dosing flexibility. We have therefore revised the expected launch date of a phase 2 clinical trial to the first half of 2025.
In the first half of this year, we further expanded our ACLF franchise by e-licensing two additional exciting programs.
In May, it was SRT015, an Ask 1 inhibitor in an injectable formulation. And more recently, in July , CLM022, which is a 13-class inflammasome inhibitor, in between sensors from Ciroiate purposes.
So ASK1 inhibition has shown several potentially beneficial effects that may be
such as blocking LPS associated
reducing the RRS-related immune response.
reducing apoptosis, reducing release of a poor inflammatory cytokines, reducing fibrosis, and protecting macrophage mitochondrial function.
A first in-human study is planned for SRT15 in the second half of 2024 to support a proof-of-concept study in ACLS patients as early as 2025.
CLM022 enables GenFit to develop a potential of an inflammasome inhibitor into liver disease indication for the first time. We will provide updates on this program as it moves closer to an IND.
The last asset in this franchise is VS02, which is a urea inhibitor, which is being developed in hepatic and cephalopathy, which is one of the major complications of advanced liver disease and portal hip intention and is closely associated to ACLF.
IND-enabling studies are targeted to be completed in 2025.
We are very pleased to have created a unique portfolio in ACLF. There is a very high unmet medical need, and we believe our deep pipeline provides us with a unique opportunity to drive value rapidly and potentially bring new hope for this patient.
Besides ACLF.
We are running our Phase 1B slash 2A program.
for the treatment of advanced cross-mutated cholangiocarcinoma evaluating our novel clinical stage autophagy inhibitor called GNS-561.
The first patient is expected to be screened in the last quarter of 2023. And the first biomarker data expected to be available as early as the first half of 2024.
should support preparation of further evaluation of efficacy with the optimal doses of TNF561 and Tramethanib in the phase 2a part of the study.
Other than ACLF and CCA, we have an earlier stage program underway with ESO1, this time developed for acute hyponomic crises associated with inbound errors of metabolism in urea cycle disorders and organic acidemia, or OA, where IND-enabling studies are targeted to be completed in 2024. We, at ESO, have a new legal mandate regarding matchup on attributed hormones and their'e extremes that define an immunocompcommandment influence stage on saccharin. Often, sometimes when weuo Lif Kenya, now including the
Last but not least, we will continue to explore partnerships opportunity for NIST2 Plus technology with the goal to release an IVD test powered by NIST2 Plus on the US and European markets. We believe this market is bound to grow now that approval of NASH drugs seems to be on the horizon.
In 2023, we've continued to have scientific publication and presentation at scientific events on NIST2+.
In conclusion, I'd like to say just a few words about GenFit corporate social responsibility.
as this was recognized by three independent stakeholders. In January , we were granted a prime status by ISS. In June , GenFit was classified by other research as best in class for ESG based on two main criteria, activity impact and ESG maturity. And in July , GenFit was awarded a gold medal by ET finance and ranked two out of 75 companies in the biopharmaceutical sector in France.
This recognition is our testament to a company-wide effort in implementing CSR initiatives and ensuring transparent communication about them. In the second half of 2023, GenFit will continue to reaffirm its commitment to associate all social responsibility and sustainable development.
I will now highlight a few key financial elements from today's press release, but I won't get into details since all numbers were already described in the documentation provided.
So as of June 30, 2023, GenFIT had 111.8 million euros in cash and cash equivalents.
compared to 140.2 million euros as of December 31st, 2022.
The decrease in cash, cash equivalents, and current financial instruments between December 31, 2022 and June 30, 2023 is largely the result of our research and development efforts, notably for Eletiv or Phase III clinical trial, FLF-Ebronol in PBC, and the IT or Phase II clinical trial for VSO1 in ACLF.
the study for GNS 561 as part of our cholangiocarcinoma program as well as the continued development of NTZ in ACLF.
As we continue to advance our current product candidates, conduct preclinical studies as well as clinical trials, we expect that our cash use in operational activities will amount to about 60 million euros in 2023.
This amount does not include potential expenses we may incur in future business development activities such as in licensing.
GenFIT's finances remain secure until the fourth quarter of 2024 based on current assumptions, excluding exceptional events and in particular, excluding potential milestone payments, which GenFIT can expect to receive following the positive interim readout of relatives.
If GenFit were to receive milestones related to a successful relative study according to potential regulatory submission and approval, as well as potential commercialization, we expect that company funding may be secured far beyond 2024, obviously assuming that all plan outcomes are favorable.
So, I guess we are now ready to take questions. So, operator, I'll let you give the instructions to the audience. Thank you. Thank you.
If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment.
Again, please press star 1 to ask a question. Our first question will come from the line of Evan Wang with Guggenheim Securities. Please go ahead.
Hi guys, thanks for taking the question. Just have a question on Elif Ebenor. Seems like both GenFit and Ipson are pretty confident in some nuance heading into A S.L.B.
So just interested to hear what kind of analysis we could look forward to at AASLD, whether it be on baseline characteristics.
different measures of biochemical response or different cuts in depridus.
Thanks.
Hi, Yvan. Well, at this point, we can't really comment further. I think both CIMABE as well as then are going to present more data at upcoming conferences and as
the sort of full day.
is made available, people will have a better idea about how the two products profile are. I think at this point, we just can't comment on what Isen is going to present.
but the ASLD is not too far out so there's not much time to wait.
And if I could ask one follow-up, you know, great to see that alpha-dens laboratory trials underway. Does that trial provide an opportunity to look at pruritus in a larger patient population?
So this trial, I mean obviously as you know, the confirmatory study is primarily designed to show the impact of the treatment on hard clinical endpoints to demonstrate that the SORGATE that are in the phase 3 are indeed productive.
of clinical endpoint. That being said, it is also an opportunity to gather much more data from a larger group of patients. So I fully expect Ibsen to be communicating on various elements through this study.
Thanks. I'll jump back to the queue.
We will take our next question from the line of Susheela Hernandez with Van Lanchett- Lanshot-Kipman. Please go ahead. Smartsie policing done by N More Automated Computer
Please go ahead.
Thank you for taking my question. First of all, could you just repeat when you expect the first milestones to come in from Ibsen and what triggers them? And as a second question, are you expecting to further build out your Iseola franchise? Thank you.
Hi, Sushila. Well, actually, we hope to get the first milestone. We hope to meet the first milestone before the end of the year, and the first milestone being to regulatory filing.
in the US and in Europe .
As far as your second question is concerned, no, I think we now have a pretty deep portfolio in ACLF. As far as I know.
No other company has more than one program in ACLS and we have now five. So the idea is not to continue to build that but to execute on the development of the VELS program.
That's clear. Thank you.
Please go ahead.
Thanks for taking my questions and congratulations.
on the data earlier in the quarter.
I wanted to ask about your growing ACLF portfolio.
You know you have this a new ask one inhibitor with with data potentially in 2025
I'm just curious you just brought this in I'm wondering if you can explain to us What specific aspects to the profile of this asset? Gives you confidence in ACLF.
And how does this sort of...
inconclusive data previously with this target in NASH Have anything to do if if at all in ACLS, and then I have a follow-up
Yes, hi Ed. So I let Dean comment on this specific Ascoani limiter and how it differed from the one that was tested in NASH by Iliad. I just want to maybe preface Dean's comment.
by talking just a little bit about the importance of medical need in ACLF.
I mean, as we know, all liver disease sort of, you know, lead to cirrhosis, regardless of the etiology, right? It could be NASH. It could be
It could be viral, it could be valetase. They all lead to cirrhosis. It could be viral, it could be valetase.
In the US, it's about 300,000 hospitalized decompensated cirrhosis per year. And about a third of those, or 100,000, go to ALS. That's the stage we're at.
So the unmet need is really high. The cost to public health is also really high since there's obviously a lot of ITO resources. So it's really important to try it and address those. So the other one is underway. And then we brought those to asset. And I let Dean comment specifically on SRT-15 and ask one in addition.
Thank you.
Hi Ed, thank you for the question. So the SRT015, as you just mentioned, is an inhibitor of S1. I think the audience probably know S1 inhibitors best.
as a position in Nash. And when it's positioned in Nash, I think most of the focus was looking at...
the inhibitors to be able to impact on fibrosis.
However, I think when you look at the mechanism of S1...
Pathway, we know that when ask one is Activated it leads to activation of downstream pathways like p38 junk
And that pathway, when it is chronically activated, which is what you have in chronic liver diseases, including cirrhosis and late-stage cirrhosis.
decompensated cirrhosis beyond the fibrosis. There's going to be benefits.
because this pathway impacts on inflammation and we know that
systemic high systemic inflammation is a real hallmark of ACLS patients.
And the other important activity of an AS-1 inhibitor is that it impacts on cell death. And as we realize that ACLS, hallmark of which is, as I mentioned, systemic inflammation, but also most often it links 21 cells to personal health, right?
organ failures, multiple organ failures. So that combination of activities on fibrosis, inflammation, as well as cell death.
I think it's going to be a potent combination to be used to address
for the treatment of ACLF patients.
The SRT-015 molecule itself I think has a wider therapeutic window than the molecules which an autogon silosative than what was used in NASH.
And I think also, CEO-ROC also has done a lot of work looking at the activity of this molecule in different disease models.
Things like acute liver failure, drug and disease liver failure, and so on. And there's some very nice positive data looking at that which of course is aligned with some data looking at specifically at the ability of...
in the meeting S1 with SRT 015 impact on key steps within the pathway.
I hope that answers your question.
I think maybe we can add that I think
Generally, what people think happened with selonsertib is that the dose was too low maybe to show efficacy. And that was because at a higher dose, there was some safety concern. And I think the folks at C-ROC have really made a convincing case that this issue does not exist.
with SRT015 which enables them to dose it at the right level for efficacy.
Great, that's very helpful. Thank you. One follow-up, if I may, before I get back in the queue, and this is sticking with your proprietary pipeline beyond El Efibonor. Given that the
The first biomarker data out of the CCA program Is probably the nearest coming up here in the first half of 24. I'm wondering if you could Give a little more detail about what exactly we can expect with that data readout. Thanks so much
I'll let Dean comment on what we can expect to see. I would just say that the
The first data we'll have is likely to be the SO1. Of course, it will depend on the rhythm of enrollment. But I think the two will be really close next year. So Dean, I'd like you to comment on GNSI-1.
Yeah, so as you probably remember, GNS561 is an inhibitor of photophagy.
And as an inhibitor, autophagy specifically inhibits PPT1, which is an enzyme towards the later stage of the whole autophagy pathway. So I think some key...
markers which we'll be assessing is the ability of this molecule to decrease the expression of PPT-1, for example. So there's different steps throughout the autophagy pathway downstream of PPT-1 we'll be looking at, but I think that is a particular one which will be of high interest.
Thanks again.
Thanks again. Our next question comes from the line of Evan Wong with Guggenheim Securities. Please go ahead.............
Hey guys, just wanted to, you know...
Great to see some of the progress there and, you know, it sounds like we're on track for a first half 24 interim read.
I just, you know, just wanted to get a sense, you know.
on how enrollment is tracking, and can you talk through some scenarios that would allow for.
expedited pathways.
is the trial size of the petition for a potential accelerate approval.
Hi Evan. So in terms of enrollment, I mean it's still early days. I mean right now we're still on track. We hope to open...
more sites in the US that are going to come online later, and that obviously help with accelerating, accelerating performance. So we're hopeful. Obviously we're breaking a little bit new ground here because there have not been a lot of ACLF trial up until now, but we're confident and will update you as we go along. In terms of,
In terms of accelerated approval, it will obviously depend on what we are able to show. I think the view is that if we can make a case that there is efficacy, there will be openness.
from the authorities because of the very high medical needs and the fact that we got the particular drug that's also a irrational thing to do onto the underlying justice field with
designation. Right now we have an LED comment about the design but we have
is the cliff score, which is a score developed by Giselle and look at the log and function. But we're also obviously looking at the
at survival and obviously if we can show something here, that would be a very strong argument to get approval. Dean, do you want to comment on the design of the study?
Sure, yeah, so before I get into that, I think another important point, and this is what we're seeing as we engage.
with different investigation centres as well as the investigators themselves. I think there's a lot of excitement and motivation from the different investigators with whom we have met and with whom we're reaching out to. I think, as you know, that's going to be a key point to be able to address.
drive the treatment of any trial. This trial is not an easy trial, but I think it's viewed as technology as an engineered liposome, and the mode of administration and all of that I think is seen as a technology that really has potential to be groundbreaking and be a real game changer. I think all these different things taken together also based on what has been seen in terms of results in the first human trial. This very compelling result I think drives a lot of excitement.
So right now the study is in phase two. We have different centers open in Europe and the design is to recruit a total of 60 patients.
So we'll have.
30 patients on treatment with VS01 on top of standard of care versus the control group which is standard of care.
Pascal mentioned the primary endpoint was the CLIF ACLF score. So the CLIF ACLF score is something that was developed by the CLIF Consortium, and this was published.
I think back in like 2014, I invite anyone who's interested to really look at that paper. I think it's published in the journal, Hepatology, really describing the development of the CLIF score, the strength of the CLIF score, and also the ability of the CLIF score to be prognostic and informed on network framers and been involved in various
on risk of mortality of these different patients.
So the CLIF score is basically a score, an algorithm, which looks at organ system function, which is composed of liver, the kidney, the brain, coagulation, circulatory, as well as respiratory, and the two other components, which it captures is age and white blood cell count to inform it on inflammation.
So again, you know, it's a score which has been developed and tested quite extensively. And you'll see in the publication that it does have a lot of evidence supporting it. So that's the primary endpoint.
And of course, the secondary end point, which is equally important, concerns mortality.
in terms of the timing of this. So the protocol itself is that we will...
Thank you.
introduce the VS01 technology into the inter-peritoneal space.
and leave it in there up for four hours. So it's a four hour dwelling time. We then drain it back out, then we do this once a day for four consecutive days. And then we follow up the patients, we keep it in the hospital up to seven days. And then we follow up at day 14, 20, and 90.
and at day 90 at the end of study.
Good afternoon. Thanks for taking the questions and congrats on all the progress.
Just a couple questions from our end. I guess first on elofibrinol, we've seen a competitor post the study in patients who are above upper limited normal, but below the 1.67 times upper limited normal criteria.
I guess can you just remind us?
how the future Elafibranor development plans are going to be implemented with IFCEN. Do they drive all of the clinical development decisions here, or are you working with them to help structure that? And how do you think about running a study in that patient population to perhaps expand, either expand the label or expand the addressable patient population and then
Just a second question on overall strategy.
Can you just give us an update on sort of your latest thoughts on business development? Are you still out there evaluating some of these other rare liver disease programs and looking to bring in additional assets or do you feel like you've kind of completed the pipeline build at this point? You're more in sort of an execution mode.
Are you still out there evaluating some of these other rare liver disease programs and looking to bring in additional assets or do you feel like you've kind of completed the pipeline build at this point, you're more in sort of an execution mode? Thank you.
Hi Tom. Look, so first of all, in terms of the development for elafimano, Ibsen is now responsible for everything. So that would include the open label part of the Phase III as well as the confirmatory study.
and obviously any new indication either in PBC similar to what CIMABE is doing to expand that market or in other indication I think Ibsen has communicated that they started
in the SC and also potentially in combination for example. So that's 100% Ibsen decision. The only sort of impact for us is should it be successful then say the Félèf Chibanno
will also give rights to royalties for Gen-FIT. But whatever choice is made there is entirely up to EBSET. That being said, I mean obviously we know the product very well, so if they have any question, we are 100% here to help, but that's their decision how they want to pursue that. For more information, visit EBSET.org
In terms of your second question, we feel that from a BD standpoint we want to pose. We have built a portfolio in ACLF that's really unique. Nobody else has anything close to that in terms of its depth and in terms of the company commitment.
to ACLF, but now, I mean, we can't keep adding. So first of all, we feel that we've covered.
the more promising pathways. And also, we need to now really be focused on execution. And we don't have the bandwidth to do much more than that. So no, don't expect anything else from a business standpoint. We'll obviously be continuously monitoring the environment. And if there's something really promising, we might change the vision. But
In terms of strategy, we feel we have something.
That's really exciting and we want to develop that.
Got it. That's super helpful. And maybe just.
One quick follow-up, if I could, on Elefrem Noor. And I was just wondering if you could comment on, I guess, whether there are any outstanding data sets that would potentially serve as a gating factor, you know, basically turning them over, I suppose, to IPSN for the regulatory submission, or whether, at this point, you know, essentially everything has been turned over, and it's just a matter of IPSN preparing the NDA and submitting the NDA on their end.
Thank you. Thank you.
Yes, we have completed the transfer. So now it's really absent in the driver's seat for the filing and also for the presentation of a much more complete dataset in the N3 conferences.
Got it. Okay, great. Yeah, super helpful. Looking forward to seeing the detailed data at ASLD and congrats again on all the progress.
helpful. Looking forward to seeing the detailed data at ASLD and congrats again on all the progress.
This does conclude today's question and answer session. I will now turn the call back to Pascal Prigent for any additional or closing remarks.
Thank you and thank you all for joining. So in conclusion I'll just reiterate that the positive results for our relative phase 3 study in PBC means that GenFit is now entering a new era and we pivot from a focus on a single program to the development of a robust portfolio of WooPROics program to DR Lights and the successful 0s going into February , which is near and dear to the Jeffrey and NancyANA system. want to give a funny start on newer treatments on this
Additional ELLITIV data will be released in the coming months and we are confident that this data will further demonstrate that Elafibarlo has a very competitive profile and the potential to add significant value to patients with PBC.
We are very pleased to see the commitment of our partner, IBSEN, and we believe that they will make the most of the opportunity. And for GenFit, essentially, this means a potential first milestone met in 2023. And if LFC 1R is approved in PBC, additional milestone and regular revenue stream for royalty payments.
These potential revenues would be used to finance the development of our pipeline with seven different programs now ranging from preclinical to phase two. As I was saying, in particular, five distinct programs in ACLF where the medical need is really significant.
So looking forward to our next corporate update at ASLD in mid-November.
Thank you and goodbye.
This concludes today's call. Thank you for your participation and you may now disconnect.