Minerva Neurosciences, Inc 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah. First, thank you for the invitation. It's been really nice to be here and to enjoy the conference, which is great. I think in just one minute about history, what we have tried to achieve with Minerva was really to address unmet medical needs in the space of psychiatry, overall neurosciences, but mostly psychiatry. I think we have been quite successful because as you probably have seen, one drug we co-developed with Johnson & Johnson went back to Johnson & Johnson, seltorexant, and I think the drug is doing very well. Our lead molecule, roluperidone, is also addressing a huge unmet medical need, which are negative symptoms in patients who have a diagnostic of schizophrenia.

This is a disease or a type of symptoms from schizophrenia, which people have tried to address since 70 years or so, since we had the first antipsychotic, and nobody was successful. We have really a drug here with a lot of hope for patients.

Yeah. This is what we are doing at Minerva.

Yeah. First of all, I think negative symptoms, people are forgetting it because, since, again, 70 years, we have antipsychotics treating positive symptoms, agitation, hallucination, delusions. We forgot a little bit about what is really the disease. The disease is about three types of symptoms, negative symptoms, positive symptoms, and cognitive impairment. What is very clear is that the first type of symptoms which occur are negative symptoms, and this occurs very early on in the life of these patients, usually when these patients are at around 15, 16 years of age. These are good kids. They're good at school, having friends, interested in whatever music or sport, and slowly but surely, they are losing the drive to do something. This is what we call amotivation or avolition, and this is one of the key driver of negative symptoms.

They're also afterwards losing the pleasure to do something they were liking to do before, which is anhedonia. These are really the two pillars of negative symptoms. The National Institute of Mental Health has called these the five A's, but avolition and anhedonia are really the main symptoms. The diagnostic will not be done there at this age, but the diagnostic will be done when you have a first episode of positive symptoms, whatever, between 18 and 25 years of age. But when you're looking backwards, you see that what is really driving the disease are negative symptoms. This is, by the way, recognized by the FDA, by the regulator, and I think by the scientific community.

It's a great question, and to be completely fair, I think there are currently two schools of thinking. One school is thinking that these patients are cognitively impaired and you have to improve cognition, which is one way to see cognitive impairment in schizophrenia. There is another school, and I'm more in favor of this school, and I will come to our data because our data are more in favor of the second school, which says these patients are not cognitively impaired, they're just not able to execute because they have negative symptoms, and particularly because they have avolition. In my previous life, I was running a research institute. When you are pushing a patient with schizophrenia to do a cognitive task, he's performing quite well. But because he has not as a drive to do it, he has avolition, he has negative symptoms, he's not executing basically.

I personally think that if you improve negative symptoms, you have a chance to improve cognition. I think there is a real link here between the two, and we have published data on two studies where we used cognitive testing and definitely our drug is improving cognition as well.

Yeah. This might be, by the way, another indication we could follow after we have the drug approved for negative symptoms.

Also big debate. But if you are going according to publications, at minimum, you are coming to the conclusion that 60% of the patients have negative symptoms with diagnostic of schizophrenia. Keep in mind that the incidence is around one person. So we are speaking here about a lot of patients, around 3 million people only in the U.S. But if you are putting the disease in a dynamic way and looking to the course of the disease, I think it is fair to say that 100% of the patients with the right diagnostic, there is also an issue about diagnostic, but this is maybe a discussion we can have another time. But patients who have real schizophrenia during the course of the disease, they might have negative symptoms during their lifespan. So I would say that 100% of the patients are suffering from negative symptoms at a certain time of the disease.