Rare Community Profiles is a Patient Worthy article series of long-form interviews featuring various stakeholders in the rare disease community, such as patients, their families, advocates, scientists, and more.
Rare Community Profiles: A Conversation with Rallybio CEO Stephen Uden on the Need for Rare Disease Drug Development
In the world of rare diseases, patient needs often far outpace available solutions. Unfortunately, this means that many patients often face long and arduous diagnostic journeys, a lack of treatment options, and poorer quality-of-life.
It’s in this space that Rallybio emerges as a groundbreaking force. At its helm is Stephen Uden, driving Rallybio’s bold mission to confront the challenging and elusive obstacles in the path to attaining treatments for rare conditions.
In Rallybio’s pipeline there are a number of therapies in development for rare conditions: RLYB212, an anti-HPA-1a monoclonal antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT); RLYB116, a C5 inhibitor for rare diseases driven by complement dysregulation; and an ENPP1 small molecule inhibitor for hypophosphatasia. Uden shares:
“RLYB212 and RLYB116 are in Phase 1 development currently, and the rest of our pipeline remains in discovery and preclinical phases. Moving forward, we hope to move into Phase 2 to show that they have a meaningful impact on patients.”
During the National Organization for Rare Disorders (NORD)’s Breakthrough Therapy Summit in October 2023, Patient Worthy caught up with Uden to discuss why Rallybio chose to focus its efforts on rare disease—and why RLYB212 has the potential to transform the treatment landscape (and maternal and fetal outcomes) within the FNAIT space. Explore with us as we dive into this captivating account where scientific pursuit meets human urgency.
About Stephen Uden, M.D.
Dr. Stephen Uden is a physician by training who received his medical training at the University of London’s St. Thomas’ Hospital Medical School before practicing clinical and academic medicine within the U.K.’s National Health Service (NHS) and at the University of Manchester.
Uden now serves as the Co-Founder and Chief Executive Officer (CEO) of Rallybio, a clinical-stage biotechnology company that is working to discover, develop, manufacture, and deliver therapeutics for individuals living with severe or rare conditions. He has more than 25 years of experience, serving in R&D leadership roles with prominent global pharmaceutical and biotech firms. He previously joined Alexion Pharmaceuticals as the Head of Research, where he led a series of collaborations and external alliances, expanding its research base beyond antibodies to include small molecules, RNA-based therapies and broader protein engineering capabilities. Uden shares:
“I have known Rallybio’s other co-founder, Dr. Martin Mackay for decades. In 2018 after our time at Alexion, we decided to found Rallybio. Alexion was transitioning to a larger pharmaceutical company. While this was absolutely the right decision for the company, Martin and I were bitten by the biotech bug. We enjoyed what we were doing at Alexion and wanted to continue within the rare disease space. As a rare disease company, we have in-licensed promising product candidates for challenging conditions that we believe we can develop for patients with unmet medical needs.”
Learn more about Stephen Uden and the rest of the Rallybio team.
Making a Difference
When asked why the company chose to focus on rare disease, Uden drove home the idea of making a difference. As many people within the rare disease community know, mobilizing support behind rare disease drug development can be challenging. These conditions are often underexplored and poorly understood; doctors may not have heard about rare conditions and may lack an understanding of disease progression. Further, many rare diseases have not been appropriately researched or studied, making it more difficult to develop drugs or other interventions. Says Uden:
“But this is what makes rare disease drug development so rewarding: to discover a way to eliminate a disease, to take it off the table, that would be the most amazing thing. I’ve been working in drug R&D for 30 years. There have been a few projects where I really think, ‘This is it. This is going to change lives.’ FNAIT is similarly prevalent to Rhesus disease, which makes antibodies against a baby’s red blood cells. Rhesus disease affected 1 in 15 pregnancies up until the 60s—and treatments now mean that it is much less prevalent. That’s what I want to do for FNAIT: find a drug that reduces its prevalence or, if possible, completely eliminates it.”
What is FNAIT?
Fetal and neonatal alloimmune thrombocytopenia is a rare immune disorder. The National Organization for Rare Disorders (NORD) explains that:
FNAIT occurs when the baby’s platelets are attacked and destroyed by the mother’s immune cells in her bloodstream [because] the platelets from the baby are identified as foreign and the mother develops an antibody response against them. As of 2022, 35 different platelet-specific antigens have been described in FNAIT.
FNAIT occurs in approximately 1 in every 1,000 births. Symptoms may appear before birth or within four weeks following birth. In mild cases, symptoms may include thrombocytopenia (low platelet levels), skin discolorations called purpura and petechiae, and hematoma formation. Severe cases are characterized by petechiae and purpura, cephalohematoma (blood collecting under the scalp), intellectual disability, seizures, bilateral sensorineural hearing loss, and bleeding in major organs. Without treatment, an estimated 26% of infants with FNAIT develop intracranial hemorrhage, or bleeding in the brain. Infants with severe symptoms are at a higher risk of life-long disability or death.
FNAIT also has considerations for mothers. Mothers of children with FNAIT could have a higher risk of miscarriage. Additionally, Uden says:
“The tragic thing is that, because FNAIT is an immune phenomenon, once the mom has one child with FNAIT, every future child is at risk. We spoke with one mother whose doctor told her that she should be sterilized, which must be such a terrifying thing to hear. There are ways to mitigate and manage for mothers, but we want to provide an option for prevention.”
RLYB212 and Clinical Trial Design
In designing RLYB212 and preparing for clinical studies, Rallybio first looked at two potential ways to treat FNAIT. The first was a polyclonal treatment where the antibody was extracted from the plasma of mothers of children with FNAIT. After connecting with Naitbabies.org, the Rallybio team conducted an outreach effort to locate mothers who could potentially serve as plasma donors. Says Uden:
“Naitbabies is a patient organization registered with the Charity Commission in the UK. The organization focuses on supporting mothers who have had babies with FNAIT, takes part in published research, and provides grants and more. It has been a tremendous resource in putting us in contact with key opinion leaders and groups in this space, and helping us to understand the disease and its impact.”
Rallybio chose to transition its FNAIT program to monoclonal treatment, which can be produced using standard manufacturing methods. The company is currently developing clinical trial designs and protocols for future research. Uden explains:
“During the pregnancy, the mom is completely well. Nobody really realizes there is a problem until the baby is born and begins bleeding from different orifices. If you treat the moms, they have a healthy pregnancy and baby. It’s a bit funny to plan clinical trials where the outcome is, essentially, that nothing happens. So, as we design our studies, we want to understand what we’re trying to avoid and if there’s anything that needs to be top of mind. Our ultimate mission is to prevent this so that no babies are born with FNAIT in the future. As we move forward, we are dedicated to our mission of developing transformative therapies and ensuring that patients can have access.
