Author: The New Economy

Gordon McCauley discusses the important quest for an effective drug combating neuro-degenerative diseases, and the successes developing their drug Davunetide.

The New Economy: How big, how important, is the question for a new drug that can treat neurodegenerative diseases like Alzheimer’s?

Gordon McCauley: You know, it’s a huge quest. First of all you have to understand, there are millions of patients around the world, suffering from Alzheimer’s and other debilitating or degenerative diseases. Probably the best way to understand that is to look at the existing market for Alzheimer’s drugs.

There are about $6bn of drugs sold today to treat Alzheimer’s disease, and all of those drugs have one common characteristic: they don’t do much.

So if you have a market of $6bn for drugs that are really not terribly effective, it gives you a sense of the scope of the human challenge behind that number. So there is absolutely a vital quest to find a truly disease-modifying therapy in Alzheimer’s disease; and of course we believe that Davunetide has the real potential to be that disease-modifying therapy.

The New Economy: Now Davunetide you’ve mentioned – the drug that Allon is developing – has shown a great deal of promise in trials so far.

Gordon McCauley: We’ve had very successful, both pre-clinical animal model trials, as well as human studies. If you look at the pre-clinical package, there’s a very significant body of data there. I think at this point it’s 35 different studies in 17 different models of Alzheimer’s cognition, memory, learning, and so on.

Some are done in our hands, some done in collaborators’ hands, some done in commercial laboratories, where we consistently see a read-out with this compound. So it’s very exciting in that respect.

It’s more exciting to look at the studies we’ve done in humans, where in our Alzheimer’s programme, we’ve seen a statistically significant improvement in memory function: working memory and short term memory. In our schizophrenia cognition programme, we’ve seen a statistically significant improvement in the functional capacity of those patients to live independently. So, can they manage their banking? Can they manage their transportation? Their medical appointments? And so on.

And also in that programme we saw a statistically significant improvement in an important brain imaging biomarker, so, a market of braincell function and integrity. So we’ve had some very encouraging data, and of course we’ll continue to follow that data as we go forward.

The New Economy: Well the principle in biotechnology is always ‘follow the data’, so where is the data on Davunetide leading you from here?

Gordon McCauley: Well absolutely, the mantra has to be follow the data. And I have to say, five or six years ago, when nobody really cared about what we were doing, we still followed the data then, because the early pre-clinical data we had at that time clearly demonstrated the potential for the compound. And we’ve consistently followed that data through time, and we’ve seen, as I say, encouraging pre-clinical data, encouraging human clinical data. We know the drug works in humans, we know that it works in a way that’s certainly relevant to Alzheimer’s disease and a variety of other dementias, so we’ll certainly continue to follow the data going forward.

The New Economy: There’s one particular area of disease which interest you in this, and that’s progressive supranuclear palsy, or PSP. What’s the potential there?

Gordon McCauley: Progressive supranuclear palsy is a debilitating disease today. These patients are typically 45-65 years old when they first get diagnosed, and this is an early-onset movement disorder and dementia.

What’s intriguing is that all of those patients have the so-called tau pathology as the underlying pathology of that disease. And that’s the pathology on which our drug appears to work. So, first of all, PSP is as close as you can come to a homogenous, or not-mixed-population, in dementias, as you can possibly find.

They also decline very rapidly. The average time from diagnosis to death is a little bit more than three years. In extreme cases of frontal-temporal dementia, of which PSP is one type, you see patients lose about 15 percent of their brain volume every year. There is no efficacious therapy whatsoever.

There is, however, a validated, well-understood rating scale, that measures clinically relevant outcomes. So at last if you put all of that together: you have a homogenous population that declines rapidly for which there is no efficacious therapy, and for which there is a well understood and validated rating scale? It meets all of the regulator’s criteria for what’s called single-study approval. So, we’re about to launch a pivotal study, the last study we believe we’ll need before we ask regulators to approve this drug, in progressive supranuclear palsy. And we’re very encouraged by it, because we think it’s a real glimmer of hope for these patients, and an opportunity to bring real disease-modifying therapy to those patients.

The New Economy: The path to drug approval can be long, demanding, expensive… so what partnerships are you making along the way?

Gordon McCauley: It is a long path; it is a demanding path. We’ve had the privilege of working with really some of the best people in the world. So in the Alzheimer’s example, we’ve had the privilege of working with Dr Paul Izen and his colleagues at the Alzheimer’s disease cooperative study, which is really the pre-eminent group in the world focused on Alzheimer’s disease.

Certainly the National Institute of Aging in the US, which funds the ADCS, has been very supportive of us as well. We’ve had the honour of receiving fairly substantive grant money from them. The TURNS Consortium, which is focused on drugs for cognitive impairment and schizophrenia, has been very supportive of us, as has the National Institute of Mental Health in the US, which supports the TURNS Consortium as well.

And presently we’re working very closely, first of all, with our founding scientist Professor Illana Gozes and her colleagues at Tel Aviv University, but also with the University of California San Francisco, Drs Bruce Miller and Adam Boxer, who are probably the leading voices in frontal temporal dementias and PSP specifically in the world.

The New Economy: Great progress so far, but you have to take the long-term view with drug development; what are the next steps for Allon Therapeutics?

Gordon McCauley: Well what you discover about the Allon team first of all is that we’re absolutely focused on execution. If you look at the promises we made to our shareholders over the course of the last five years, we’ve done pretty well exactly what we told our shareholders we were going to do. So going forward, the first priority without question is initiating this pivotal study in progressive supranuclear palsy, which we’ll do over the next short period of time.

There’s also a second generation product we’re developing that will focus exclusively on Alzheimer’s and schizophrenia. There are other products in our pipeline: an interesting one that we’ll look to bring into human testing in the next year or so that has shown quite interesting promise in chemotherapy induced neuropathy, or the pain associated with cancer treatment. And there appear to be opportunities to work on other compounds as well.

So there’s a lot to do, but again, our team is absolutely focused on executing and the lion’s share of our energy will go towards the pivotal study in progressive supranuclear palsy.