Annette Bakker, PhD, Chief Executive Officer of the Children’s Tumor Foundation, discusses repurposing shelved assets for rare diseases.

The Children’s Tumor Foundation is an organization dedicated to developing treatments for patients with neurofibromatosis (NF). NF is a group of rare genetic conditions that cause tumors to develop in the nervous system. The main types of NF are Type 1 (NF1) and NF2-related schwannomatosis (NF2-SWN). Symptoms can include skin changes, bone abnormalities, optic gliomas, and tumors on the nerve tissue or under the skin, acoustic neuromas, hearing loss, ringing in the ears, poor balance, brain and/or spinal tumor, and cataracts at a young age. Schwannomatosis causes schwannomas, pain, numbness, and weakness.

Dr. Bakker recently spoke about the importance of repositioning drugs for rare disease at the 2025 World Orphan Drug Congress (WODC). When small biotech companies begin development on a new drug and then are bought out by major pharmaceutical companies, these drugs may become shelved assets. This means the drugs to do get further developed and initiatives are stopped, typically for business and strategic reasons. Because these drugs still have efficacy and safety potential and usually, phase 1 data, they are a huge opportunity for the rare disease community.

The challenge lies in getting the rights to these treatments and out of the companies they are being held in. Further challenges arise from the project team being reassigned or no longer at the company, unorganized data, and convincing upper management of the decision to repurpose.

Despite these challenges, two drugs have recently been approved through this process. With the help of the CTF, systems are being put in place to further progress in repurposed drugs. A preclinical hub has been set up to quickly derisk assets and platform trials allow companies to place their drugs into testing. The foundation currently has about 60 ongoing clinical trials.

Chapters:
Introduction 00:00
The Children's Tumor Foundation 00:30
Repositioning Drugs for Rare Diseases 1:01
Challenges With Shelved Assets 2:33
Success Stories 3:42
Finding Clients and Funding 5:37

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Alison Bateman-House, PhD, Assistant Professor Division of Medical Ethics at NYU Grossman School of Medicine, discusses ethical concerns in rare diseases and expanded access programs.

Rare disease patients, caregivers, and healthcare practitioners often face unique challenges. This includes the ethical concerns involved in drug development, clinical trials, and treatment plans. Some of these ethical concerns include deciding which rare diseases to develop drugs for. Some rare disease communities have a lot of sponsor interest due to being seemingly easy to develop a drug or being a guaranteed money maker. However, many rare diseases do not have any drug development programs.

Ethical concerns are also evident in the designing of clinical trials where researchers have to choose which patient populations will be enrolled. Oftentimes, choosing between the least-affected patients versus most-affected or whether to include children or adults. Interesting questions arise in the use of children in clinical trials, such as allowing parents to make difficult decisions on behalf of their children, or waiting until the children are old enough to make their own decisions. This leads to further concerns about drug effectiveness at different disease stages and when to best start treatment to slow disease progression.

Additionally, rare disease communities are often well-networked and tightknit and clinical trials are small. Parents may struggle with balancing emotions of grief and empathy for other families, while still needing to keep their own interest in mind. For example, learning that a child has been rejected from a clinical trial, supporting the families of those involved, while trying to get their child enrolled in these limited slots.

Dr. Bateman-House explains how Expanded Access Programs can be beneficial to rare disease patients and communities. Expanded Access Programs are a pathway for patients to access drugs and treatments that are currently unapproved by any regulatory agencies. These treatments are only typically available to those enrolled in a clinical trial. However, because of the small populations in rare diseases and the prominent need for therapies, these treatments can be beneficial to the patients that receive them.

There is a large need for education about clinical trials and Expanded Access Programs. Both in regards to how best to develop such initiatives in ways that are beneficial to the rare disease patients and in getting messaging out to families to raise awareness about their options.

Chapters:
Introduction 00:00
Rare Disease Ethical Issues 00:35
Expanded Access Programs 3:29
Need for Education 4:50

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Connie Lee, PsyD, Chief Executive Officer of Alliance to Cure Cavernous Malformations, discusses cerebral cavernous malformation (CMM) and the diversity of patient advocacy group initiatives.

CMM is a rare, capillary-venous malformation characterized by closely clustered irregular dilated capillaries that can be asymptomatic or that can cause variable neurological manifestations. These can include seizures, non-specific headaches, progressive or transient focal neurologic deficits, and/or cerebral hemorrhages. About 70% of people with CMM are unaware of the condition until a major event occurs and they are formally diagnosed via MRI. About 25% of patients have an autosomal dominant genetic form that can be detected with genetic testing.

The Alliance to Cure Cavernous Malformations was founded about 23 years ago and has since developed a robust network of patients, researchers, and clinicians. They provide free genetic testing for patients as well as centers of excellence, virtual support groups, patient navigation services, and patient conferences.

As Dr. Lee explains, patient advocacy groups are vital to the rare disease community. Her presentation at the 2025 World Orphan Drug Congress (WODC) highlighted ways in which industry partners can evaluate and find benefit in patient advocacy groups. While patient advocacy groups focus on providing support and resources to patients, many of them are also involved in the basic and translational science communities.

Dr. Lee and her colleagues put together a guide that shows all dimensions of patient advocacy groups and the diverse initiatives that they have in hopes that industry partners gain knowledge and see ways in which these organizations can be beneficial partners.

Chapters:
Introduction 00:00
Cerebral Cavernous Malformation Overview 00:22
Diagnostic Journey 1:33
Alliance to Cure Cavernous Malformations 2:34
Understanding Patient Advocacy Groups 3:57

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Yuri Maricich, MD, Chief Medical Officer of CAMP4 Therapeutics, discusses the company’s current drug development programs.

CAMP4 is a biopharmaceutical company focused on utilizing RNA to develop novel treatments that increase gene expression in patients with rare genetic conditions.

CAMP4 is currently working on CMP-CPS-001, a novel investigational therapy designed to address the underlying cause of urea cycle disorders (UCDs) by regulating genes associated with the condition. The first clinical trial of this program was initiated in March 2024 with a phase 1 single-ascending dose study in healthy volunteers. Following the completion of this trial, a multiple-ascending dose study was initiated.

Recently, the company announced a phase 1b expansion of this study in an ornithine transcarbamylase (OTC) heterozygote population. Upon completion of this extension, the goal is to transition into a phase 3 registrational clinical trial in the second half of 2026.

A second treatment is being developed for SYNGAP1-related disorders. While CMP-SYNGAP is not yet in clinical trials, encouraging results have come from testing in animal models. The company has plans to present data at this year's American Society of Gene & Cell Therapy meeting (ASGCT 2025).

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David Curren, patient advocate and board member for Breath of Hope Rhode Island, discusses the organization and his grandson’s diagnostic journey.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease characterized by repeated episodes of bleeding into the lungs, which can cause anemia and lung disease. The body is able to remove most of the blood from the lungs, but iron accumulation can lead to fibrosis in the lungs. Symptoms can resemble pneumonia and include coughing, coughing up blood, difficulty breathing, and wheezing. The cause of IPH is unknown.

As Mr. Curren explains, diagnosis of this disease can be difficult due to symptoms resembling those of other more common diseases. His grandson was in the ICU for two weeks before a lung biopsy was performed and an IPH diagnosis given.

Breath of Hope Rhode Island is currently raising funds for the University of North Carolina Children’s Research Center where a patient registry is being put together. The organization also focuses on raising awareness for IPH providing support for the community.

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Johannah Rossell, Senior Vice President and General Manager of Rare Diseases at Sumitomo Pharma America, discusses best practices for navigating challenges of the orphan drug market and provides personal experience through her work with congenital athymia.

Congenital athymia is a rare disease characterized by the absence of a functioning thymus and is commonly associated with several genetic and syndromic disorders. Congenital athymia can result from defects in genes that impact thymic organ development such as FOXN1 and PAX1, among others.Athymic patients often present with absent T cells but normal numbers of B cells and natural killer cells. Patients with congenital athymia have profound immunodeficiency, increased susceptibility to infections, and frequently, autologous graft-versus-host disease.

Rethymic (allogeneic processed thymus tissue-agdc) was the first tissue-based treatment to be approved by the U.S. Food and Drug Administration (FDA) in 2021 for congenital athymia. The treatment is developed from thymus tissue and reengineered to target patients’ ability to develop an immune system.

Ms. Rossell recently gave a presentation at the 2025 WODC meeting where she gave valuable insight into navigating challenges of the orphan drug market and provided examples of her work with Rethymic. She noted four main challenges that pharmaceutical companies face when trying to commercialize their drug and get it in the hands of rare disease patients.

The first challenge is generating robust data with clinical meaningfulness. This is key in gaining an FDA approval can be challenging in rare disease populations where numbers are small.

Secondly, pharmaceutical companies face complex manufacturing challenges when dealing with novel therapies. Ms. Rossell stresses the importance of scalability in companies while sticking to practices that are sustainable but can allow for the effective treatment of patients.

The third challenge is demonstrating the value in a product to both the healthcare system as well as patients. This is done through creating effective programming and messaging that gets the word out about a treatment to those populations.

With the last challenge, Ms. Rossell describes how to take advantage of different regulatory approval pathways. These may include specific designations such as Regenerative Medicine Advanced Therapy, Breakthrough, Rare Pediatric Disease, Orphan Drug, etc. The achievement of such designations is important in being able to have more conversations with regulatory agencies and learning what they want to see to help better the chances of a treatment approval.

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Arezou Khosroshahi, MD, Associate Professor of Medicine at Emory University School of Medicine, discusses the approval of Uplizna (inebilizumab-cdon) for treatment of immunoglobulin G4-related disease (IgG4-RD).

IgG4-RD is an immune-mediated condition that can affect multiple organ systems. Common features include IgG4-related autoimmune pancreatitis, swelling within an organ system, salivary gland disease, swollen lymph nodes, skin manifestations, and symptoms consistent with allergies or asthma. The cause of IgG4-RD is unknown. Prior to the approval of inebilizumab, treatment of IgG4-RD mainly consisted of the use of glucocorticoids.

Inebilizumab is a humanized monoclonal antibody that targets the depletion of autoantibody-producing CD19+ B cells that contribute to the underlying disease. It is administered as two initial infusions, followed by one dose every six months.

The FDA approval follows positive data from the MITIGATE trial. This study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial evaluating the safety and efficacy of inebilizumab in reducing risk of flares in adults with IgG4-RD. The primary endpoint was time to first treated and adjudicated IgG4-RD flare. Secondary endpoints included annualized flare rate, flare- and treatment-free complete remission, and flare- and corticosteroid-free complete remission.

Key findings observed in this study included an 87% reduction in the risk of flare compared to placebo and a reduction in annualized flare rate for treated and adjudicated flare at 0.10 for patients receiving inebilizumab compared to 0.71 for patients receiving placebo. Additionally, 57.4% achieved flare-free, treatment-free, and complete remission at week 52 compared to 22.4% for the placebo group. Achievement of flare-free, corticosteroid-free, and complete remission at week 52 was at 58.8% in the inebilizumab group, and 22.4% in the placebo group.

The safety profile of inebilizumab was favorable. The most common adverse events in patients were urinary tract infection and lymphopenia.

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Al Freedman, PhD, Rare Disease Psychologist and Rare Dad, discusses how industry partners can support the mental health of rare disease communities.

Dr. Freedman provides individual counseling, support group facilitation, and advises rare disease advocacy organizations and industry partners on mental health needs. His presentation at this year's World Orphan Drug Congress (WODC 2025) focused on how industry partners can support the mental health of rare disease communities.

Some of the unique mental health challenges that rare disease families face include the trauma of diagnosis and adjusting to life-changing news, navigating a new life of anxiety-inducing uncertainty, and how to find hope and strength in their community. Scientific progress can also contribute to the mental health of those in the rare disease community. The addition of newborn screening and new treatment options bring hope to patients and families. However, progress can also present new challenges such as ethical issues, access to treatment, and funding. Despite these challenges, Dr. Freedman has repeatedly observed the ability of rare disease patients to be more resilient, creative, and have a better perspective than persons without rare conditions.

Because the priorities of industry partners and rare disease community members often differ, Dr. Freedman stresses the importance of finding the intersection of those priorities and investing in a mutually beneficial partnership. Industry partners that do the best in these communities are those that get to know patients and families, listen to their needs, and respond with actions that address those needs. Earning trust and listening are the top ways for industry partners to support the mental health of this community, along with initiating sponsored programs such as workshops, support groups, and peer support.

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Yuri Maricich, MD, Chief Medical Officer of CAMP4 Therapeutics, provides an overview of urea cycle disorders (UCDs) and discusses developing novel therapies.

UCDs are a group of rare, inherited metabolic disorders caused by deficiency of one of the six enzymes in the urea cycle responsible for removing ammonia from the blood stream. The most common of these enzymes are OTC, ASS, and ASL. Urea is a byproduct of the metabolism that, in normal cases, is converted to urea and removed from the blood. However, in UCDs, nitrogen builds up in the blood in the form of ammonia, resulting in hyperammonemia. Common symptoms include vomiting, lethargy, seizures, and developmental delays. In more severe cases UCD can lead to irreversible brain damage, coma, and death.

Current treatments for UCDs focus on managing ammonia levels through dietary restrictions, medications, and in severe cases, liver transplants. The condition has no therapies that target the underlying cause of disease.

CAMP4 is currently working on CMP-CPS-001, a novel investigational therapy designed to address the underlying cause of UCDs by regulating genes associated with the condition. The first clinical trial of this program was initiated in March 2024 with a phase 1 single-ascending dose study in healthy volunteers. Following the completion of this trial, a multiple-ascending dose study was initiated.

Recently, the company announced a phase 1b expansion of this study in an OTC heterozygote population. Upon completion of this extension, the goal is to transition into a phase 3 registrational clinical trial in the second half of 2026.

Chapters:
Introduction 00:00
Urea Cycle Disorders 00:50
Clinical Trials 4:10
Challenges of Diagnosis and Clinical Trial Enrollment 5:27
Developing Novel Treatments 6:06

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