Jean-Pierre Sommadossi: Obviously, we will finalize any protocol with the regulatory authorities. But based on our initial interaction, it’s clear that a comparator is required for our Phase 3 program.
Unidentified Analyst: Thank you very much.
Operator: And one moment for our next question. And our next question will be coming from Roanna Ruiz with Leerink Partners. Your line is open.
Rosa Chen: Thank you. This is Rosa Chen on for Roanna Ruiz, Leerink Partners. Just a couple from us. First on COVID. So thinking of all the various high-risk patients you’re enrolling in Phase 3, which subpopulation do you think bemnifosbuvir can offer the most differentiated profile from currently available antivirals? And any thoughts on how you could leverage the data from the combination therapy arm?
Jean-Pierre Sommadossi: Janet, do you like to address the question, please?
Janet Hammond: Sure. So, I think, with regard to the high-risk patient population, I mean, it’s quite interesting, but I think in the last few months, there have been a couple of publications really showing that for the most high-risk patients, the elderly, particularly, I think there’s 75 and above and those that are highly immunocompromised, and I think in that regard, particularly solid organ transplant patients. However many times they get vaccinated, it doesn’t really seem to reduce their risk of getting severely ill when they do become infected with COVID. So, I think these are the patient populations, which are probably the ones where there is likely to be the great benefit. And I think another reason why ultimately I think bemnifosbuvir would be an ideal drug for patients such as these is that these are patient populations that are on multiple concomitant medications.
And as Jean-Pierre mentioned, and as we’ve alluded to, I think the potential for drug interactions, particularly with protease inhibitors is much higher than with nucleoside antagonists. And so, I think these are the patient populations where frequently, they’re actually ineligible to receive a drug such as Paxlovid and have been in the past fortunate enough to have been able to receive monoclonal antibodies. But as you know, the monoclonal antibodies haven’t been able to keep pace with the evolution of the virus. And then, with regard to the combination group and what we’re going to do there to educate ourselves, it’s really — the most important, I think because we have, as Jean-Pierre mentioned in his remarks, a protease inhibitor, which is being developed in which we hope to show more information for later in the year.
And so, I think being able to see how combination therapy and in particular, a protease inhibitor in combination with bemnifosbuvir is able to provide synergy and potentially reduce severity symptoms and allow patients to improve better. And also, we’re again looking at such things as drug interactions, viral load kinetics and safety and tolerability. I think all of that information is important in understanding how best to use these drugs and maximize them as we move further down the line.
Rosa Chen: Thank so much. And then, on HCV, how should we think about the PK and efficacy of bemnifosbuvir and ruzasvir in the patient population that actually has compensated cirrhosis compared to those without cirrhosis in your leading cohort? And then, are you considering including patients with decompensated cirrhosis and also HIV co-infection in your Phase 3? So, it’s a similar — was to pursue a similar label as Epclusa? And then separately, who are these low-hanging fruit patients that you could target if it’s approved?
Jean-Pierre Sommadossi: So, Arantxa, maybe you want to start to address the question, and then we have maybe a comment as well. So, Arantxa?
Arantxa Horga: Yes. Well, I think the PK, we don’t anticipate major changes in PK or even PK/PD and viral kinetics as you saw in the data that we have shown. The kinetics were very fast even in the F3s, which are really borderline compensated cirrhotic. So, we think that — and we’ve seen also in previous trials that the PK should be the same. That is for the compensated cirrhotics. For the decompensated cirrhotic, it is a great population. I think that we are going to target it. It’s probably a little bit later. For the HIV, certainly, we are considering inclusion in Phase 3 trial. It’s like you said, a great unmet need population.
Jean-Pierre Sommadossi: Yeah. No, actually, just one comment for the decompensated patients, obviously, that would be, we believe, a major advance because we foresee — at least, we see the potential to eliminate ribavirin, which right now, you have only one approved treatment, which is a combination of Epclusa and ribavirin in those patients. Now, let’s not forget that this is patient population that is very difficult, very likely in a trial, you are going to have some deaths. So, obviously, we foresee that this population will be very likely not part of the Phase 3 program unless the regulatory authorities will request that, but more as a post NDA commitment. But definitely, we definitely want to go there, maybe not with eight week, probably a 12 week would be already highly differentiated with the elimination of ribavirin.
And obviously, these patients do require the best chance of success and that the length of treatment are less of an importance than what we have with the patient population that Arantxa just shared with you before.
Rosa Chen: Got it. Thanks so much for taking our questions.
Jean-Pierre Sommadossi: You’re welcome.
Operator: Thank you. I would now like to turn the conference back to Jean-Pierre for closing remarks.
Jean-Pierre Sommadossi: Thank you all for joining our fourth quarter and full year 2023 earnings conference call, and thank you as well for your continued support.
Operator: Ladies and gentlemen, this concludes today’s conference. You may now disconnect.
