A leading strategy in a very big race

Billions are spent every year in advanced economies on drugs for Alzheimer’s disease, yet none of these drugs can halt or even delay its progression. The story is similar for schizophrenia: billions spent annually on drugs to treat the psychoses that torment schizophrenics, but no approved drugs for the cognitive impairment that is the real impediment to patients’ productive engagement in society.

Here are two enormous opportunities to help millions of patients and their families and to save billions in public health care costs. Everyone knows the largest international pharmaceutical companies – the so-called Big Pharma – are constantly looking for blockbuster drugs to replace revenue from others that continue to fall off their income statements – and these two opportunities certainly qualify. So what is our emerging company, Allon Therapeutics Inc., doing in the thick of this race?  Interestingly, we are not getting run over. In fact, we seem to be among the leaders at the front of the pack.

In numerous animal studies, we have shown that our drug, davunetide, halted brain cell degeneration and improved memory. In a clinical trial in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s, davunetide had a statistically significant positive impact on memory. In a clinical trial in schizophrenia patients, davunetide demonstrated it could improve the capacity for daily functioning of these patients. In that same study, we showed through imaging that davunetide had a statistically significant impact on an important chemical marker of brain cell health.

These trials were carried out by some of the top physicians and researchers in the world and reported at the leading scientific conferences and in journals. Our journey began six years ago when a number of us met the founder of Allon, Professor Illana Gozes.

Davunetide and related compounds were discovered by Prof. Gozes, of the Sackler Faculty of Medicine at Tel Aviv University. Her work was supported by visionary philanthropists, Tel Aviv University, and the US National Institutes of Health (NIH). Prof. Gozes derived davunetide from a naturally occurring neuroprotective brain protein that she discovered, known as activity dependent neuroprotective protein (ADNP). Prof. Gozes, with her colleagues at Tel Aviv and the NIH, demonstrated the significant potential of davunetide in numerous models of Alzheimer’s and neurodegeneration. It was clear then, and is even clearer today, that davunetide could be the leading therapy in the so-called tau pathway of Alzheimer’s and dementia. At the time, however, the generally accepted scientific focus was on other approaches.

We decided to build a business around the significant potential that we saw regardless of industry’s focus elsewhere. We made this decision based on the first principle of biotechnology: follow the data. These data were compelling then and have become even more so after numerous human clinical trials. While following the data is the first principle, we built a business based on common sense.  That is: it’s all about people. We assembled an outstanding team with deep scientific, drug development, and business experience. The team works effectively together, does what it says it’s going to do and, most importantly, shares a passion to help patients and families suffering from cruel and debilitating disease.

Over the past six years, our team has consistently produced animal studies with compelling data in models for Alzheimer’s, schizophrenia, frontotemporal dementias, peripheral neuropathy, and other learning and memory deficits. We’ve shown that our lead drug candidate works in humans, that it works in a way relevant to the patients we’re committed to helping, and we can measure its impacts directly in the human brain. We’ve worked with, and been supported by, the key opinion leaders and public institutions.  

Yet we still have to get this product approved, and studies in Alzheimer’s are long, difficult, and expensive. More disheartening is the fact that it has been about eight years since a novel therapy was approved in Alzheimer’s. In the meantime, there have been numerous high profile and expensive failures. There appear to be basic questions about the approval path, the heterogeneity of the Alzheimer’s population, and the tests used to prove efficacy.

We began to look for a unique and more rational approach – and that is when we learned about progressive supranuclear palsy (PSP), a type of frontotemporal dementia (FTD). Approximately 20,000 and 50,000 people are diagnosed with PSP annually in the US and EU respectively, and it is often characterised by progressive difficulty with balance and walking, eye movement abnormalities, and cognitive and personality changes. Patients are typically diagnosed when they are 45 to 65 years old. PSP is associated with progressive disability and death often a little more than three years following diagnosis.

FTD, including PSP, gradually damages or shrinks the front of the brain – the frontal and anterior temporal lobes. Patients gradually lose the ability to behave appropriately, empathise with others, learn, reason, make judgments, communicate and carry out daily activities. FTD affects approximately 200,000 people in the EU, and a similar number of Americans, or about 6.7 people per 100,000 among people ages 45 to 64.  In people under the age 60, FTD is the most common cause of early-onset dementia. FTD can be mistaken for Alzheimer’s disease, Parkinson’s disease, or a primarily psychiatric disorder like depression, manic-depression, obsessive-compulsive disease, or schizophrenia. There is no efficacious therapy for these patients.

A clear path to approval
We believe that an efficacy study in PSP is not just a unique approach – it is also the right one for Allon and davunetide. We are about to launch a robust human clinical trial in PSP because:

• Our existing data support the hypothesis that davunetide works on tau impairment (or “tauopathies”);
• PSP patients are an homogenous population all of whom have the tau pathology on which davunetide seems to work;
• Sadly these patients decline very quickly and there is no effective therapy; and
• There is a validated rating scale that measures clinically relevant outcomes.

Given these facts, we also believe that our study for davunetide in PSP can qualify for single study approval – meaning that this next study may well be the last required before we ask regulators to approve davunetide for PSP. And regulators have responded positively to this point: davunetide has been granted Orphan Drug status in the US and EU, and it has been given Fast Track status in the US as well. The medical community has responded similarly. We are pleased that one of the world’s leading FTD medical teams, from the University of California San Francisco Memory and Aging Center, as well as many other key medical leaders, has been actively engaged with us.

It is also important to note that this next trial will not just provide data for a potential approval,  it will also help define the opportunity in other tau-related diseases, such as several other types of FTD, as well as Alzheimer’s and schizophrenia. This unique approach may well lead to davunetide being the first approved therapy that actually modifies these diseases. More importantly, we believe that it may bring hope and relief to millions of people and families suffering with cruel and debilitating neurodegenerative disease.

Further information: www.allontherapeutics.com