At n-Lorem, every investment decision carries real weight by directly affecting the nano-rare patients we serve. We think very deeply about each decision of how to invest the limited and precious dollars that we have. But what about investing in basic research to advance antisense oligonucleotide (ASO) technology for the future? Certainly, most of the money should and is being put towards creating ASOs to help patients in need today. Meanwhile, it is also our belief that we must invest to continue innovating and, in this episode, we explore the research occurring at n-Lorem today that will lead to better treatments for more nano-rare patients tomorrow. On this episode we discuss: - ASO technology is still evolving unlike other validated drug discovery technologies

- Nano-rare patients need more from ASO technology

- Reasons n-Lorem are unable to help more patients

• Loss of function mutations
• Mutations that cause dysfunction of an organ to which ASOs distribute at only high doses
• Innate immune activation
• Challenges in creating allele-selective ASOs

- Solutions to these challenges are possible and we know how to do it

• Advances in loss of function mutations
• Targeted delivery to muscle, the immune system, the gut and heart
• Controlling innate immune activation
• Enhanced allele-selectivity

Links:

Colloquium - https://www.nlorem.org/nano-rare-patient-colloquium-2025/

Donate - https://www.nlorem.org/donate/

The Data Safety Monitoring Board (DSMB) is composed of distinguished, independent experts in antisense oligonucleotide (ASO) technology, clinical trial design and evaluation, and drug development. Many are also dedicated clinicians who care for patients with rare diseases. This board provides unbiased safety oversight by reviewing accumulated data from all investigator-initiated studies involving n-Lorem’s ASO medicines.

n-Lorem's DSMB is chaired by Dr. Eugene Schneider, Executive Vice President and Chief Clinical Development and Operations Officer at Ionis Pharmaceuticals.

On This Episode We Discuss:

• 2:20 – What is the Data Safety Monitoring Board at n-Lorem?
• 6:50 – Monitoring the data from each and every treated n-Lorem patient is essential
• 9:40 – The DSMB consists of a collection of physicians and other experts
• 13:20 – As the number of n-Lorem patients grows, the DSMB’s responsibilities have expanded significantly—yet members remain deeply committed to supporting the mission
• 17:05 – The DSMB’s goal is to avoid any ASO-related serious adverse events (SAEs) and minimize adverse events
• 19:20 – During his time as Chair of the DSMB, Eugene has learned lessons in patience and humility
• 21:00 The judgements of monitoring boards can and will affect lives

Links: n-Lorem 2025 Nano-rare Patient Colloquium: https://www.nlorem.org/nano-rare-patient-colloquium-2025/

Donate to support n-Lorem programs: https://www.nlorem.org/donate/

Hongene Biotech: https://www.hongene.com/

Connor Gooley is the first patient ever treated with an ASO for TUBB4A-Related Leukodystrophy, a condition that severely disrupts his nervous system, slows nerve impulses, and impairs his fine motor skills. As a result, Connor cannot speak, walk, sit up on his own, or chew well. Still, he manages to army crawl, propel himself in his wheelchair, and use a gait trainer. He’s also remarkably resilient—rarely crying or complaining despite the daily challenges he faces.

In this episode of the Patient Empowerment Program, Connor’s parents, Diana and Mike, share their family’s journey from diagnosis to treatment and reflect on their observations of Connor after more than six months on an n-Lorem discovered and developed treatment.

On This Episode We Discuss:

1:33 Shaking eyes were the first sign of Connor’s rare disease

4:10 An MRI revealed little to no myelin, leading to whole genome sequencing and an eventual TUBB4A genetic mutation diagnosis

7:10 Connecting with another family with the same mutation

10:00 Finding n-Lorem through a ‘seeking patient candidates’ advertisement in a Global Genes annual report

12:26 Contextualizing Connor’s TUBB4A mutation in simple terms

21:19 How rare diseases affect families and creating a new normal

27:41 Receiving treatment in Boston and contemplating the decision to agree to an experimental treatment for their son

32:00 Observations after 6 months on treatment

35:45 n-Lorem has given the Gooley family hope for a better future for Connor

Links:

Hongene Biotech: https://www.hongene.com/

Donate to n-Lorem / Support nano-rare: https://www.nlorem.org/donate/

n-Lorem 2025 NRPC: https://www.nlorem.org/nano-rare-patient-colloquium-2025/