Maximizing Molecules and Medicines

From the discovery of new molecules to lifecycle management of our approved medicines, Horizon scientists and technical experts are relentlessly and compassionately exploring potential new treatments for patients with rare, autoimmune and severe inflammatory diseases.

Our team is committed to solving difficult problems and is not afraid to explore paths less taken to create the next generation of innovative therapies that serve patients around the world. We follow what the data tell us, resulting in a curated pipeline of targeted experimental medicines and novel mechanisms of action.

Watch to learn more about the Horizon research and development (R&D) team’s practical and creative approach to thinking differently about science:

Creative Approaches to Experimental Medicines

In this section, we explore how our scientists and technical experts are investigating targeted therapies to treat a variety of diseases. At the center of our scientific approach are premier pathways – those that have a central role in aggregating the many biological inputs that lead to disease and the transition from an early disease state to a more severe condition. First, we explain the origination and development of different diseases in the body. Then, we dive into the experimental medicines our team has developed as a potential solution. Take a look.

Lysophosphatidic acid (LPA) is a bioactive molecule that works through several receptors (LPAR) on a human cell. Dysregulated signaling via LPAR1 can cause leaky blood vessels, inflammation and fibrosis, leading to diseases such as idiopathic pulmonary fibrosis (IPF) and diffuse cutaneous systemic sclerosis (dcSSc).

As a potential solution, HZN-825 is a molecule that blocks one of the receptors, LPAR1, and has been shown to reduce collagen deposition, fibrosis and the molecules involved in signaling to immune cells, preventing and potentially reversing the disease processes.

Plasmacytoid dendritic cells (pDCs) are present in high numbers in tissue and constantly activated in certain autoimmune diseases, which causes them to secrete large amounts of inflammatory molecules, especially Type 1 Interferons. This can lead to a variety of autoimmune conditions.

As a potential solution, daxdilimab (HZN-7734) is an anti-ILT7 human monoclonal antibody that has been shown to deplete plasmacytoid dendritic cells (pDCs) and reduce levels of these cells and Type 1 Interferons. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, alopecia areata, discoid lupus erythematosus, dermatomyositis and lupus nephritis.

CD40 is a well-established receptor pathway that contributes to autoimmune and inflammatory disease when it binds to the CD40 ligand (CD40L) causing B cell and T cell interaction that creates inflammation and disease.

As a potential solution, dazodalibep (HZN-4920) is a novel, non-antibody fusion protein that blocks CD40L activity, that has been shown to reduce B cell activation and autoantibody production, potentially halting inflammation and autoimmunity and diseases such as Sjögren’s syndrome, rheumatoid arthritis, kidney transplant rejection and focal segmental glomerulosclerosis.

FLT3L drives the production and survival of plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs), which contribute to inflammation in the body. Many autoimmune and inflammatory diseases have higher levels of circulating FLT3L levels which are thought to support the prolonged inflammation observed in these conditions.

As a potential solution, HZN-1116 is an anti-FLT3L human monoclonal antibody that binds and neutralizes the function of FLT3L and has been shown to reduce the levels of pDCs and cDCs, thereby decreasing the inflammatory molecules they produce, which could potentially reduce prolonged inflammation in a variety of diseases.

Overheard in the Lab

Our scientists are committed to working together to discover and develop novel treatments for patients in need. Watch as they take you behind the scenes.

Science Stories

Our scientific teams are exploring ways to bring novel small molecules, potential first-in-class biologics and new medicine administration options to patients.

'Premier Pathways' Are the Heart of Our R&D Strategy

At Horizon, our research and development (R&D) approach to scientific discovery is all about premier pathways that lead to a variety of diseases.

Read more

A New Approach to Target Dysregulated LPA Signaling

What if there was a way to target dysregulated signaling in one receptor while allowing five other receptors to continue normal activity?

Read more

Halting Inflammation Through CD40 Ligand

Our team is thinking differently about halting disease activity that leads to inflammation through CD40 ligand.

Read more

A Novel Approach to Target pDCs in the Body

Horizon scientists are exploring a new approach to reducing autoimmunity that leads to diseases like lupus.

Read more

People Behind the Science

Our work at Horizon is personal. Our R&D team is fueled by more than 300 scientific minds across the company.

Yaminah Leggett-Wells, M.S., MBA, senior director, alliance management, believes that when diverse mindsets from academia and biotechnology come together, it can create powerful partnerships that ultimately help patients. “Many diseases in our pipeline disproportionately affect people of diverse backgrounds - in order to accurately reflect these communities in our science work, we need to bring diverse perspectives to the table at the early stages of clinical development,” Leggett-Wells said. “Having thought leaders connect with our teams and potential partners, including those in international markets, helps us design better protocols for our clinical trials to ensure we’re meeting the needs of all people living with these diseases.”

At Horizon, Leggett-Wells and her team focus on advancing the company’s business development and scientific collaborations from early drug discovery to on-market medicines. She specifically focuses on seeking academic collaborations that will have a synergistic effect on advancing Horizon’s pipeline and providing new treatments to patients. “When we look for potential academic partners, we try to identify institutions that understand the biology behind the disease states we’re focused on and can help us bring targeted therapies for those patients,” Leggett-Wells said. “Having this kind of partner will make us more efficient in our work, allowing us to get therapies to patients sooner.”

Sadiye Rieder, Ph.D., associate director and research scientist, spends her days in the lab asking questions about how autoimmunity develops in humans. As the leader of Horizon’s early preclinical programs, she builds research strategies to uncover new information about autoimmune diseases that have limited treatment options. She is specifically looking at T cells and the role they play in preventing these diseases. “If you understand the biology of how different cells work in the body, you can break down these disease processes and create targeted medicines that can help patients,” Rieder said.

Asking questions about scientific processes is what initially sparked Rieder to follow her career path. At a young age, she wanted to understand why people developed certain diseases. She credits several influential female mentors for empowering her to translate her autoimmune disease research into something meaningful for others. At Horizon, she aims to do the same with her female colleagues and those she mentors. “Knowing I can inspire young women to pursue a career in science by showing them that their work can ultimately turn into something life-changing for patients is what fuels me every day.”

Bill Rees, Ph.D., Horizon’s leader in translational medicine, is focused on science that puts an emphasis on people as individuals rather than on the patient population as a whole, a discipline he calls “Big Science.” Rees leads toxicology, bioanalytic, pharmacology and translational medicine teams to produce the data needed to understand diseases. “Our team recognizes that one medicine isn’t going to fit all patients with the same disease, which is unique in biotech,” Rees said.

Rees and his team work closely with Horizon’s clinical development and medical affairs teams to examine and tell the story of how Horizon’s molecules interact with the human body. He is a strong believer in the benefit of collaboration to help break down barriers and spur growth. “True strength is not in white papers or guideline documents; it’s in the people and collaboration across all functions,” Rees said. He also looks across therapeutic areas to explore treatments to help patients manage their diseases. “Our goal is to bring the right medicine, right dose and right timing to the right patient.”

Articles and Publications

Our team’s discoveries and scientific findings extend beyond the lab. Review some of our scientific publications and articles below:

Preclinical Manuscripts

Clinical Manuscripts

Review Articles

View Horizon's R&D fact sheet here.