Lloyd Miller, M.D., Ph.D., Vice President, Immunodermatology Disease Area Leader at Janssen Immunology, spoke with Jason Witherington, Vice President of Immunology Scientific Innovation at Janssen about his career journey as a clinician-scientist and why he is optimistic about the next generation of potentially transformational therapies for patients living with immune-mediated skin conditions. Johnson & Johnson Innovation captured the discussion below.
What led you to become a dermatologist?
As a MD-PhD clinician-scientist, my decision to become a dermatologist combined my desire to provide excellent patient care for skin diseases (that are often lifelong) with my strong interest in investigating immune responses. In inflammatory skin diseases, the inflammation in the skin can be seen with skin manifestations such as redness, swelling, scales, blisters, abscesses, and hair loss, which enable dermatologists to readily diagnose patients and monitor the response to treatment.
What inspired you to leave academia to join industry?
After 20 years in academia where I treated patients, taught medical students, residents, and fellows, and directed a basic and translational research laboratory, I decided to join industry hoping to make an impact in the development of next-generation, transformational therapies for patients living with immune-mediated skin diseases. In addition, I was particularly excited about the Immunodermatology Disease Area Leader position at Janssen to build on prior successes in psoriasis and conduct clinical research in other immune-mediated skin diseases in which there are limited therapeutic options and high unmet need.
Has your view of industry changed since you joined?
Since I joined Janssen more than a year and half ago, I have been extremely impressed with my colleagues, specifically their brainpower and “one team” spirit. Everyone at Janssen is focused on working to bring improved therapies to patients. This level of focus is truly inspiring. It’s why I enjoy going to work every day.
How great is the unmet need for patients with atopic dermatitis (AD)?
Patients living with AD can experience chronic itchy skin, which often begins in infancy and is a lifelong disease in many patients. The itchy inflamed skin and constant scratching can lead to sleep disturbance and high rates of anxiety, stress, depression and suicide. In AD, there continues to be significant unmet need as patients aren’t experiencing full clinical remission with available treatments. AD patients are also at an elevated risk of developing other allergic diseases, such as asthma, seasonal allergies, and food allergies, further exacerbating the disease burden.
How are AD patients currently treated?
Patients living with AD can experience itchy skin rashes with frequent disease flares. Patients living with mild AD are typically treated with topical corticosteroids, calcineurin inhibitors and oral anti-itch medications (such as antihistamines) to reduce itch. Patients with moderate-to-severe disease (>10% body surface area involved) are traditionally treated with phototherapy, oral corticosteroids and other immunosuppressant therapies. The first biologic therapy was approved for treating AD in 2017. It works by blocking the signalling of specific inflammatory mediators thought to contribute to inflammation in AD.
Where do you see the need for innovation for patients with AD?
I noted earlier that the vast majority of people living with AD are not experiencing full remission, and therefore the need for continued innovation is urgent. Currently, there are other therapies in development that specifically target IL-13, a known driver of inflammation, and inhibit Th2 cell responses, as well as oral and topical Janus kinase (JAK) inhibitors. Janssen has ongoing trials with a therapy that blocks IL-1α, which is a key inflammatory mediator in the skin, thought to reduce Th2 and other T-cell inflammatory responses. Of course, early intervention is extremely important to prevent long-term impact on patients.
“We are at the beginning of a golden age of scientific innovation.”
Recent approaches in the field of AD have had a strong focus on the Th2 pathway, what emerging pathways/approaches do you see on the horizon?
Inhibition of the Th2 pathway is one pathway in AD. There are other mechanisms involved in this highly heterogenous disease with different clinical presentations and disease-driving mechanisms. AD patients have an impaired skin barrier in which environmental allergens, microbial components, and toxins exacerbate the skin inflammation of the keratinocytes in the epidermis and immune cells in the dermis. AD patients also have an altered skin microbiome associated with disease flares. In AD skin, in addition to Th2 cells, there are also Th22, Th17 and Th1 and other cell types that contribute to the disease and their interactions between neurons that contribute to itch and pain with immune cells. There are many efforts to target these other mechanisms to provide additional therapies to AD patients.
Beyond AD, where is the greatest unmet need in dermatology?
There are several other immunodermatology diseases with high unmet need - either no approved therapies or only a single therapeutic option. These include hidradenitis suppurativa, alopecia areata, palmoplantar pustulosis, vitiligo, and bullous pemphigoid.
What synergies do you see between large pharma, biotech’s and academic KOLs?
Large pharma, biotechnology companies, and academic investigators will need to collaborate and work together to bring transformational therapies to patients. Many initial scientific discoveries in a specific disease are made by academic investigators and these can be translated to therapies by biotechs and large pharma. Large pharmaceutical companies, like Janssen, play an essential role as they have the capabilities and resources to accelerate clinical development, scale-up manufacturing and globally distribute new therapies to patients worldwide. Working together, we can advance our common goal of improving patient’s lives.
“Large pharma, biotechnology companies and academic investigators will need to collaborate and work together to bring transformational therapies to patients.”
What areas of innovation/science are you passionate about from a partnering perspective?
We are at the beginning of a golden age of scientific innovation with advances in ‘omics technologies (such as transcriptomics, genomics, metabolomics and others), digital health and medical imaging coupled with big data, real world evidence and computational biology. Partnerships among large pharma, biotechnology companies and academic researchers are needed to fully leverage these advances and provide the deep scientific understanding of diseases to develop safe and effective and targeted therapies for patients living with immune-mediated skin diseases.
Johnson & Johnson Innovation seeks to positively impact human health through innovation. We do this by helping entrepreneurs realize their dreams of creating healthcare solutions that improve peoples’ lives around the world.
Working on a transformational idea that aligns with our priorities? Get in touch with the team today by clicking here.
To learn more about a Johnson & Johnson Innovation Immunology Flagship event, Making Precision Medicine a Reality in Immune-Mediated Diseases, and to register, visit here.