The National Organization of Rare Diseases (NORD) describes multiple sclerosis (MS) as a chronic neuroimmunologic disorder involving the brain, spinal cord and optic nerves. MS is just one of 7000 known diseases categorized as a “rare disease,” but in addition to its rare disease classification, it is also autoimmune – meaning the body’s immune system wrongfully targets its own healthy tissue when initiating an immune response.

In the case of MS, the targeted healthy tissue is the central nervous system, which sustains an ongoing series of inflammatory attacks. These attacks lead to the scarring of the myelin sheath – the protector of the nerves around the brain and spinal cord. These attacks occur unpredictably, vary in intensity and affect multiple locations of the nervous system tissue – hence the name multiple sclerosis.

During the course of MS, patients may have attacks (relapses or exacerbations) that gradually worsen or stabilize. Some people with severe MS may lose the ability to walk independently or at all. 2.3 million people worldwide have an MS diagnosis, for which there is currently no cure. However, there are biotech companies searching for new therapies as well as a cure, including Apitope based in the UK and Belgium. Apitope is developing potential first-in-class antigen-specific immunotherapeutics targeting the immunological basis of autoimmune diseases.

Apitope researchers use their novel, proprietary discovery platform to select and develop highly specific peptide-based therapies, known as apitopes®, which restore the natural balance (immune tolerance) of the immune system. This mechanism of action avoids global immune suppression which protects against autoimmune diseases such as MS. Apitope’s lead product candidate, currently in Phase II clinical development, is ATX-MS-1467. It is the first potential therapeutic for MS that combines high efficacy with an excellent, and thereby differentiating, safety profile.

Leading Apitope is their Chief Executive Officer Hayley French. Dr. French has over 20 years’ experience in the life sciences sector.

Before joining Apitope, Dr. French spent three years at Novartis, based at their Basel headquarters. Prior to Novartis, Dr. French worked in the Life Sciences Group of Bird & Bird, London. Previously she was Head of Commercial Legal Affairs at the Centre for Applied Microbiology and Research (CAMR) in Salisbury UK.

Dr. French has a B.Sc. in Microbiology from the University of Liverpool, as well as a PhD in Microbiology and a M.Sc. in intellectual property from the University of London.

As part of a new series on rare diseases, WuXi AppTec Communications explored the issues and challenges of rare disease research with Dr. French and why her company’s lead drug could become the first cure for MS.

WuXi AppTec: What are the differences between developing drugs for rare diseases and for more common diseases?

Hayley French: Developing drugs for rare diseases has additional challenges, especially in the recruitment of patients in rare disease populations. There is generally a lack of knowledge about such diseases, and this presents diagnostic problems as well as challenges in clinical design, such as a lack of clinical end-points.

WuXi AppTec: Following up on what you said, can you speak to the specific regulatory and business challenges to drug development for rare diseases? Do regulatory incentives help encourage rare disease research?

Hayley French: First there are a limited number of patients for trials. A rare disease in the EU is defined as one that affects less than one in 2000. In the US a rare disease is defined as affecting fewer than one in 200,000. In fact, most rare diseases affect far fewer people. With such small patient populations, it becomes more complicated and more costly to recruit for randomized clinical trials.

Another challenge is a lack of knowledge of the history of the disease, which also adds to the complexity in designing a clinical trial. Most rare diseases are genetic diseases, which can make it even harder to research because there are different versions of the same disease. An additional difficulty is that almost 50 percent of patients suffering from a rare disease are children. This results in added ethical considerations and limits in designing clinical trials.

Fortunately, both EU and US regulatory agencies along with rare disease patient groups have increased regulatory and financial incentives for drug companies to target and develop therapies for these long-underserved patient populations.

WuXi AppTec: How much progress has been made in multiple sclerosis drug research and development over the last 20 years?

Hayley French: While the past 20 years have brought many significant advances in the management of multiple sclerosis, with the approval of over a dozen disease modifying therapies (DMTs) and numerous palliative treatment options, significant unmet needs still remain in the market. There has been a lot of activity in a busy market and many approvals of blockbusters with increasing levels of efficacy. However, with increasing efficacy we have observed safety and side effect issues. Also, there is still a need to slow down neurodegeneration and halt disease progression.

Furthermore, drugs for progressive forms of the disease have been under-researched for this underserved patient population. This has led to pharmaceutical companies focusing research and development efforts on their currently marketed relapsing MS products to treat this form of the disease.

WuXi AppTec: Your lead drug is aimed at MS, can you tell us what you have seen so far in your clinical research?

Hayley French: Apitope’s lead product candidate ATX-MS-1467 is currently undergoing Phase II clinical development. It is a potential first in class treatment specifically for MS that combines high efficacy with an excellent safety profile. Clinical studies performed so far by Apitope have demonstrated a significant reduction in brain lesions as well as the volume of brain lesions, both of which are associated with the disease. It has also demonstrated a highly favorable safety profile. Importantly, in addition to its safety and efficacy profile, Apitope’s drug has the potential to be differentiated from other therapies in halting disease progression and improving cognition.

WuXi AppTec: Different companies use different targets to treat a disease. How is your approach to MS different from other companies?

Hayley French:  Our approach is focusing on correcting the cause of the disease by acting to downregulate the specific T lymphocytes that destroy the myelin insulation of the nerves. To target a very specific T cell population the rest of the immune system is left to fully function to protect the patient from other issues, e.g. infections and cancer. Current therapies are addressing a broader cell population or a cell function which induces a general immune suppression, which results in increased susceptibility to opportunistic infections as a consequence. By inducing immune tolerance by establishing a specific set of T regulatory lymphocytes known to be missing in autoimmune diseases, the aggressive myelin-specific T cells are silenced and the disease goes into remission.

WuXi AppTec: Dr. French you mentioned the importance of your drug’s safety profile. Can you elaborate? What is the advantage to the patient?

Hayley French: The treatment has been demonstrated to be very safe with no severe adverse events, which will allow for the treatment of  newly diagnosed patients. With a continuous maintenance treatment after establishing the immune tolerance, the Apitope peptide drug can prevent the progress of  MS into more severe forms of the disease.

WuXi AppTec: Why do you see ATX-MS-1467 as a possible cure for MS? What other approaches could also be a cure for MS?

Hayley French: From our perspective, Apitope therapies treat the underlying cause of the disease by selectively reinstating immune tolerance to the self-antigen target. We believe our MS therapeutic. ATX-MS-1467 has the potential to halt disease progression rather than just slowing down the disease. Additionally, further development is being pursued on re-myelination, which could create new myelin sheaths to protect the brain and spinal cord cells.

WuXi AppTec: As a closing thought, Dr. French you have a long and successful record in drug development. What do you see as the best new technology that can really shape the future of healthcare?

Hayley French: Although still in its infancy, pharmacogenomics and its role in personalized medicine is likely to be a game-changer  and become routine standard of  medical care over the coming years. Utilizing genomics technology in drug development in the future will determine how individuals respond to drugs and have the potential to provide more effective, safe and well-tolerated individualized drug therapies.