N=1 Collaborative

A hallmark feature of The N=1 Collaborative Inaugural Annual Meeting were the stellar presentations by trainees during the Emerging Researchers flash talks. This session featured six 5-minute flash talks from graduate students, residents, and post-docs each working to develop individualized oligonucleotide-based therapies for patients. The future of ultra-rare medicines is looking promising with these talented and bright minds driving the way! Thank you to Boxun Zhao, Robert Thompson, Christiana Wang, Jack Morgan, and Caroline Johnson Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

During this week of thanks, we’re proud to recognize Microsynth AG for joining The N=1 Collaborative Donated Resource Center by contributing antisense oligonucleotides (ASOs) tailored for screening purposes. These ASOs are a crucial resource, helping to accelerate early stage therapeutic development. Microsynth AG joins a growing community of companies—including Argonaut Manufacturing Services Inc., Hongene Biotech Corporation, 3billion, Charles River Laboratories, Jeeva Clinical Trials Inc., and ChemGenes—united in the mission to advance individualized treatments. This collaborative model connects academia, industry, and patients, paving the way for broader access to life-changing therapies. Interested in contributing? Contact Nicole Nolen to learn how your company can join us. Every donated resource brings us closer to a future where individualized therapies are more accessible to real-world patients. Developing an individualized therapy? Explore the Donated Resource Center and apply today! https://lnkd.in/ew-Y3K_Z

Dive into the newly released N=1 Collaborative VARIANT guidelines, educational videos, and eligibility calculator designed to assess genetic variant eligibility for antisense oligonucleotide therapies. In this interactive workshop, lead authors David Cheerie and Marlen Lauffer will guide participants through real-world examples, offering hands-on experience and direct Q&A with the experts. Join us Tuesday, December 10, 2024 at 10:30pm US EST: In-Depth Look at Eligibility Assessment with N1C VARIANT Authors https://wix.to/2oIMmhg

Thank you to Michelle Hastings of the University of Michigan, and Yael Shiloh-Malawsky of the University of North Carolina at Chapel Hill for presenting late-breaking clinical updates for their ASO therapeutic, Zebronkysen, developed for two sisters with CLN3 Batten disease at The N=1 Collaborative Inaugural Annual Meeting. Named after their stuffed animals Zebra and Monkey, their work highlights how patient-first collaborative teams can change the medical paradigm. Michelle Hastings, Yael Shiloh-Malawsky, Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

We were thrilled to debut the N1C VARIANT (Variant Assessments towards Eligibility for Antisense Oligonucleotide Treatment) guidelines at The N=1 Collaborative Inaugural Annual Meeting! This initiative offers a comprehensive set of resources including training videos, practice test variants, and the N1C Eligibility Calculator, all designed to support clinicians and researchers working with rare disease patients. Led by Marlen Lauffer and David Cheerie, this initiative was developed by the N1C Patient Identification working group and a committed network of global volunteer assessors. We’re excited to share this valuable tool with the community. Join our hands-on workshop in December, and explore the guidelines and resources on our website: N1C VARIANT. https://lnkd.in/dyNWurnf Marlen Lauffer David Cheerie Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

Join us in welcoming Julia Alterman to the N=1 Collaborative Seminar Series to discuss Fibrodysplasia Ossificans Progressiva (FOP) - a devastating, ultra-rare condition, where patients acquire bone in muscle and connective tissue either spontaneously or in response to injury. Caused by a mutation in the ACVR1 receptor, and exacerbated by inflammatory response, excessive bone grown means patients with FOP do not often live past the age of 40. Using an siRNA chemical architecture ideal for delivery to muscle, they have developed a combinatorial treatment for FOP targeting both the mutant ACVR1 receptor and an inflammatory cytokine. This approach supports significant reduction in bone growth in a mouse model of disease and may provide a promising new therapy for the treatment of FOP. You're invited to an N1C seminar https://wix.to/sYY23W7

Thank you to Scott Demarest, Associate Professor at the University of Colorado Anschutz Medical Campus, for his presentation during the Best Practices session of The N=1 Collaborative Inaugural Annual Meeting on his experience leading experimental therapies through clinical trials for patients in an academic setting. Insights from his presentation: 1) Team matters! Academic clinical trials requires many key players including: a PI, trial coordinator, nursing, regulatory support, pharmacy, compliance, database management, and more. 2) Institutional buy-in is a critical feature of academic clinical trials – work with your institution to find an executive champion who can advocate for your team and the work. 3) The continue-discontinuation trial criteria will be different than a traditional trial. Discussions with the patient and family about what success looks like will be an ongoing conversation for the team. Conversations about expectations should happen early and often, even before a patient is started on treatment. Scott Demarest Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

Thank you Jonathan Watts, Professor at UMass Chan Medical School, for presenting on ASO Design and Safety during the Best Practices session of the Inaugural Annual Meeting of The N=1 Collaborative. Jon described traditional ASO design and the collaborative efforts across multiple institutions to identify and predict features of an ASO that may lead to toxicity, as well as how to anticipate these issues before ASOs reach patients. Additionally, he highlighted the N1C’s collaboration with La Jolla Labs Inc. to characterize and accelerate functional ASO designs for N=1 cases. Jonathan Watts Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

Thank you to Richard Finkel, MD of St. Jude Children's Research Hospital for his presentation on innovation and perspectives on Clinical Trial Design for rare diseases at The N=1 Collaborative Inaugural Annual Meeting. Highlights from Dr. Finkel’s talk: 1. Clinical outcomes are essential to gauging success of an experimental treatment. 2. Clinical outcomes for n-of-1 or n-of-few clinical trials will look different than traditional clinical trials in large populations. Key outcomes for n-of-1 or n-of-few clinical trials will prioritize: safety outcomes, non-clinical efficiency outcomes (target engagement, biomarker levels), clinical efficacy outcomes (including patient and parent reported outcomes). 3. Multiple single patient INDs (1+1+1+…) will likely be the path forward followed by small scale clinical trials. Once clinical outcome assessments (COA) are developed for one disease or patient, it will need to be explored if the COA can cover multiple ASOs and patients with the same disease. Richard Finkel, MD Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine

Thank you to Tim Yu, Co-Founder of The N=1 Collaborative and Professor of Genetics and Genomics at Boston Children's Hospital for his presentation of a hopeful message during the Strategy Session at the N1C Inaugural Annual Meeting, looking from N of 1 to N of Many. Insights from his talk: 1) Current Status of the Field: Mila and Milasen have shown that individualized medicines are possible. Ongoing research is focused on determining whether customized patient ASOs can be consistently replicated. The current strategy aims to make the development of individualized medicine both rigorous and scalable. 2) The IDEAL Model: The IDEAL model—Idea, Development, Exploration, Assessment, and Long-term Follow-up—provides a framework for iterative learning that advances medicine, born from the surgical field. 3) Applying the IDEAL Model: The IDEAL model offers a tactical perspective on developing and following up on individualized ASOs for patients. Tim Yu Jillian Belgrad Stefanie Leonard, MSN, RN Geri Beaty Annemieke Aartsma-Rus Nicole Nolen Erin M. McConnell, Ph.D., Winston Yan, MD PhD, Tim Yu Julia Vitarello Hugh Hempel Holm Graessner Nicole Boice Nina Green Ashley Kuniholm Margaret Meserve, MS, CGC Erika Fullwood Augustine Scott Demarest Richard Finkel, MD John Keilty Marlen Lauffer Rebecca Schüle Jonathan Watts Melody Joy Paine