Dr Carol Routledge (CEO) Alzinova

Dr Carol Routledge (CEO) Alzinova

 

After being dormant for some time, things are finally starting to happen in Alzheimer’s research. Alzinova is one of the companies striving to develop a vaccine that will slow the progression of Alzheimer’s disease, with the goal of creating a treatment that is both effective, well-tolerated and has acceptable side-effects. Today, we meet Alzinova’s CEO, Dr. Carol Routledge, who has already been a member of the board for many years. In this interview, she will tell us more about, the successful PHASE-1 study, how the company’s vaccine candidate works, how the path to a partnership agreement with a larger pharmaceutical company might look like and why Alzinova is likely to succeed!

 

1: Refresh our readers memory, how does Alzinovas vaccine candidate ALZ-101 work, and what is it for?

Dr Carol Routledge (CEO) Alzinova: Alzinova’s vaccine (ALZ-101) is being developed for the treatment of early Alzheimer’s Disease and for patients mild-cognitive impairment.  Ultimately, ALZ-101 could also be used to treat patients with pre-synatic Alzheimer’s Disease.  ALZ-101 is a very selective and specific vaccine.

It works in the same way other vaccinations work in that injection of the ALZ-101 vaccine will stimulate the body to make its own antibodies against particular proteins found within the body, and in this case within the brain.

In the case of ALZ-101, these proteins are the toxic amyloid-beta oligomers that are thought to cause Alzheimer’s Disease.  So, an ALZ-101 vaccination raises antibodies that bind to, and destroy the toxic oligomers in the brain, and in so doing so should help to protect against Alzheimer’s Disease.

ALZ-101 differs from other vaccines such as AC Immune’s vaccine and other beta-amyloid antibodies, because it only binds to the toxic amyloid-beta oligomers, rather than to other types of beta-amyloid.

By being so selective some of the side-effects that have been seen with these other drugs should be reduced. In addition, because it is so selective, ALZ-101 may also be more effective but we need to show this beneficial profile in our clinical trials.

 

2: Why do you think Alzinovas treatment/vaccine is better that the current treatments that today are on the market, or somewhere in the FAS-1 to FAS-3 process?

Dr Carol Routledge (CEO) Alzinova: Part of this answer was addressed in the answer to the first question, however, I would also add here: We already know that targeting beta-amyloid in the brain will be effective, the marketing of lecanemab and donanemab, antibodies that target beta-amyloid, has shown that.

These treatments have shown for the first time that it is possible to slow down the progression of Alzheimer’s Disease which gives significant hope to both the scientific researcher community and to patients and their families.

However, Alzinova’s approach is very specific and very selective for the toxic so-called amyloid-beta oligomers.

Because Alzinova’s treatment approach is predicted to only neutralize the toxic oligomers then it should have a better side effect profile and may also show better treatment effects though Alzinova need to demonstrate this in their clinical trials.

In addition, because Alzinova is developing a vaccine, rather than a therapeutic antibody, the costs to society should be significantly lower than that of antibodies.

The vaccine will be given 3-4 times per year rather than 13-26 times per year.

 

3: Tell us a little bit about yourself! 

Dr Carol Routledge (CEO) Alzinova: Since completing a PhD in neuroscience and neuropharmacology 38 years ago, I have focussed my career  on drug discovery and drug development within UK and US based pharmaceutical and biotechnology companies.

My experience and expertise in R&D has been gained largely from focussing on neuroscience as a therapeutic area.

In particular, my experience in Alzheimer’s Disease has evolved from developing treatments for neurological indications within a number of pharmaceutical and biotech companies but also working for Venture Capital who managed a research effort focussed on drug acquisition and drug profiling of NCEs and biologics.

In addition, I spent a significant period of time as Director of Research at Alzheimer’s Research UK, a non-profit organisation focused on funding research in this area.

I was introduced to Alzinova almost 7 years ago, and became a Board member based on my convictions that their approach should result in drugs that were not only safe and well tolerated, but that also provided significant benefit to patients by slowing down the progression of their disease and alleviating their dementia symptoms.

 

4: Can you walk us through the process from where you are today, to let us say you will sign an agreement with a pharma partner, just hypothetically!

Dr Carol Routledge (CEO) Alzinova: Alzinova is currently completing their Phase 1b study for their lead candidate ALZ-101, a vaccine being developed to slow down or stop the progression of Alzheimer’s Disease.

The vaccine is predicted to do this by inducing the body to raise its own antibodies against toxic proteins in the brian, the so-called beta-amyloid oligomers, which are suggested to be one of the causes of Alzheimer’s Disease.

This study is evaluating the safety and tolerability of ALZ-101 in patients with early Alzheimer’s Disease or with mild cognitive impairment, an earlier stage of Alzheimer’s Disease.

Importantly, it is also measuring the ability of the vaccine to stimulate the release of the bodies own antibodies and it is based on this latter effect that we can understand how well the vaccine might slow down the progression of Alzheimer’s.

In addition, we are also measuring the effects of the vaccine on various Alzheimer’s Disease biomarkers in this study.

Alzheimer’s Disease biomarkers are signals in the body that may tell us what biological effects the vaccine may be having, and how well we think this will be in slowing down the progression of disease.

The information from this study will be key in helping us understand how effective this treatment approach may be, and it is on this basis that we are currently in discussions with pharmaceutical companies, and others, who may be interested in partnering Alzinova to take this treatment forward into larger Phase 2 and Phase 3 studies.

 

5: What is your goal, regarding time, to have signed a Pharma partner deal?

Dr Carol Routledge (CEO) Alzinova: Our goal is to have a partner on board when we move forward to Phase 2 and then Phase 3 studies.

 

6: If you succeed, what would it mean?

Dr Carol Routledge (CEO) Alzinova: If we succeed, it would mean we have a partner to work with us on realising the full potential of ALZ-101 and potentially ALZ-201.

It would enable us to really demonstrate the advantages of developing such a selective approach to neutralising/removing the harmful beta-amyloid proteins which we think underpins the progression of, and potentially the cause of Alzheimer’s Disease.

This would be so impactful for patients and their families and could also inform approaches to the treatment of other neurological diseases.  A deal comparable to those that have recently been completed in this space would be good!

 

7: What is your view on the deal announced with AC Immune and Takeda? 

Dr Carol Routledge (CEO) Alzinova: Any positive news in terms of funding the development of novel treatments that may alleviate the suffering of patients and patient’s families is a significant step forward, and so of course, I am very positive about this news.

AC Immune also have a vaccine approach that is different to Alzinova’s approach in that it is less selective for the toxic oligomer proteins, but nonetheless, it is an approach that should provide benefit to patients with Alzheimer’s Disease.

That AC Immune’s drug is slightly ahead of ALZ-101 is potentially very helpful to Alzinova as this may help to pave the way for vaccine treatments in this area of neurology.

 

8: What is the main difference between Alzinovas vaccine candidate and ALZ 101 and AC Immunes? 

Dr Carol Routledge (CEO) Alzinova: The main difference between these treatment approaches is the selectivity of the vaccine.  ALZ-101, Alzinova’s vaccine generates antibodies in the body that bind to just the beta-amyloid toxic oligomers i.e. proteins thought to cause Alzheimer’s disease.

They do not bind to any other beta-amyloid proteins in the brain such as the non-harmful oligomers, fibrils or plaques.

The antibodies generated by AC Immune’s vaccine bind to a number of different types of beta-amyloid proteins, harmful and non-harmful. Based on the differences in selectivity of these approaches we would predict that the side effects of these vaccines would differ, with ALZ-101 likely to have the better side effect profile.

In addition, the difference may also impact how well the vaccines work in terms of neutralizing the harmful oligomers and in doing so, delaying the onset of dementia symptoms.

 

9: What does Best in class compound mean in Alzinovas case?

Dr Carol Routledge (CEO) Alzinova: ALZ-101 has been described as having the potential to be ‘Best in class’, this means that even though it has a similar mode of action or biological mechanism to other drugs that are being developed to slow down the progression of Alzheimer’s Disease, it will have a better safety and profile and potentially a better effect on dementia symptoms than they do.   So it may not be the first of this kind of drug to be approved, but it might be the best.

 

10: What are the three most important tasks that you will start to deal with immediately as a new CEO?

Dr Carol Routledge (CEO) Alzinova: Given I have been a Board member of Alzinova for almost 7 years now, I already have a very good understanding of what the Alzinova Team are aiming to achieve, and this has made the transition to acting CEO relatively smooth.

But there is still much to get onboard with and these include, not in priority order’

• Really getting to know the Team, who they are, what they do, and what their ambitions are but also ensuring that everyone is aligned on the discovery and development plans for taking Alzinova’s two lead assets towards the market and towards patients
• Ensuring Alzinova gets heard, which means releasing appropriate information on the progress of Alzinova’s pipeline and ensuring news flow reaches investors, scientific researchers and importantly patients and their families
• And, based on the above two tasks, ensuring that I put Alzinova in prime position for partnering so that we really can take these assets forward for the benefit of patients

 

11: Nothing is ever certain, but from your experience, what are the most important results in the FAS-1b study that makes you believe that Alzinova has a fair chance of moving on to the next level?

Dr Carol Routledge (CEO) Alzinova: The most important results to come out of the ongoing Phase 1b study, being conducted in patients with early Alzheimer’s disease and with mild cognitive impairment, is that ALZ-101 is safe and very well tolerated.

The second most important result is that vaccination with ALZ-101 stimulates the body’s immune system to produce antibodies against the brain’s toxic oligomers and that these antibodies have effects on the various biomarkers that we are measuring in this study.

Changes in these biomarkers would provide evidence to show that the antibodies are doing what they need to do to slow down disease progression.

The results from the trial are slowly becoming available and we should be able to talk a little bit more about them in the 4th quarter of this year and early next year.

 

Dagens Börs thanks Dr. Carol Routledge (CEO of Alzinova) for a very interesting interview, and we wish her and Alzinova the best of luck in the future!