NACFC 2025: Key Takeaways for the Final 10%

By Chandra Ghose, PhD, Chief Scientific Officer at Emily’s Entourage

From the misty shores of Puget Sound to the buzzing halls of the convention center, Seattle came alive this fall with the energy, innovation, and determination of the cystic fibrosis (CF) community. United by a shared mission to push the boundaries of CF research and care, NACFC 2025 showcased scientific innovation poised to deliver therapies and treatments that could transform the lives of the final 10% of the CF population that does not benefit from existing CFTR modulators and that is desperately waiting for breakthroughs. 

At the heart of this energy was Emily’s Entourage (EE), hosting our 8th annual reception on Friday, October 24, 2025. More than 105 CF researchers, clinicians, biotech leaders, pharmaceutical representatives, and community advocates from around the world came together to celebrate collaboration, connection, and the progress being made across the CF community. 

This year’s reception was especially meaningful for a number of reasons. We presented the inaugural Dr. Carolyn Denning Trailblazer Award to Batsheva Kerem, PhD, a visionary in CF genetics whose pioneering work—from helping identify and clone the CFTR gene to developing innovative nucleotide-based therapies for rare and difficult-to-treat mutations—has transformed our understanding of CF and opened new paths toward life-changing treatments. Presenting the newly named award to Dr. Kerem felt especially apt given that Dr. Denning herself was also a pioneer in CF care whose groundbreaking work, compassionate care, and lasting mentorship as a CF physician and researcher laid the foundation for the progress we see today. 

Additionally, this year’s Trailblazer Award was a custom work of art created and presented by Dylan Mortimer, a nationally and internationally exhibited artist and double lung transplant recipient living with CF. Dylan’s glitter-filled paintings, sculptures, and installations bring the lived experience of CF to life in striking and provocative ways. It was particularly meaningful to have Dylan present the award to Dr. Kerem himself. 

As the evening unfolded, EE Chief Scientific Officer Dr. Chandra Ghose shared updates on our latest grants as well as EE’s CF Clinical Trial Connect (CTC) and Clinical Trial Matchmaking Program, programs that accelerate clinical trial recruitment for individuals that do not benefit from available modulators. These programs are a critical bridge between life-changing research and the people who need it most.

Now that NACFC 2025 has come to a close, I’m excited to share a glimpse of the most inspiring scientific developments—advances that are generating real momentum and hope for the final 10% of the CF community still waiting for life-changing therapies.

1. Skipping Ahead: A New Approach for Nonsense Mutations

For some mutations, the body’s own quality control systems act like a roadblock, destroying ribonucleic acid (RNA) before it can produce a functional protein in a process known as “nonsense mediated decay.” This is exactly the challenge of the W1282X mutation. Batsheva Kerem, PhD, presented her latest work on SPL23, an antisense oligonucleotide (ASO) that directly addresses this obstacle. By promoting exon 23 skipping, SPL23 bypasses the nonsense-mediated decay mechanism that normally prevents modulators from working for this mutation. When combined with a CFTR modulator therapy, this approach significantly restores CFTR protein function—turning what was once an impassable roadblock into a viable path toward treatment for this mutation. This work is in addition to SPL84-002, its ongoing global Phase 2 study evaluating SPL84, the Company’s lead antisense oligonucleotide (ASO), for the treatment of people with cystic fibrosis (CF) carrying the 3849+10 kilobase (Kb) C->T splicing mutation in the CFTR gene.

2. Fixing the Stop Sign: Targeted Therapy for G542X

Nonsense mutations act like a premature stop sign, resulting in truncated, not fully functional protein production. Andrei Korostelev, PhD—a 2025 Emily’s Entourage Translational Research Grant recipient—showed how readthrough antisense oligonucleotide (R-ASO) therapy is designed to overcome this barrier. 

Unlike conventional readthrough approaches that can cause harmful side effects, R-ASOs selectively target disease-causing premature stop codons. His team is focusing on the G542X mutation, with early work demonstrating restoration of full-length CFTR protein safely and effectively. By addressing this molecular “stop sign,” R-ASO therapy opens up therapeutic possibilities for individuals with CF unable to benefit from currently available modulators. 

3. Rewriting the CF Gene: A Full Replacement for Lung Stem Cells

Imagine being able to rewrite a faulty genetic instruction manual at its source! That is no longer just a dream; it is the principle behind Sriram Vaidyanathan, PhD’s work to replace the entire CFTR gene in airway stem cells using CRISPR-Cas9. 

By modulating how cells repair DNA, his team has dramatically improved success using viral-based delivery, while demonstrating that non-viral approaches remain less effective due to cellular mechanisms not yet fully understood. This research brings the possibility of a long-lasting, mutation-agnostic therapy closer to reality, offering hope for all people with CF, including the final 10%.

4. A Universal Fix: Lentiviral Gene Therapy Moves into Humans

Delivering a functional gene to the lungs and making it stick has been a longstanding hurdle in CF therapeutic delivery. Jane Davies, MB Chb, provided an update on lentiviral gene therapy, using a third-generation vector carrying the full-length CFTR gene. 

Already in first-in-human clinical trials, this mutation-agnostic approach is designed to provide efficient, long-lasting gene expression across different CF mutations. By effectively “installing” a working copy of the CFTR gene in lung cells, this therapy tackles the root of the disease and could potentially be “curative” not only for those that don’t benefit from existing modulators, but for anyone with CF, regardless of their mutation.

Why This Matters for the Final 10%

Every insight, every conversation, and every breakthrough at NACFC 2025 brings us closer to a future where CF can be eliminated for everyone with the disease. For the final 10% still waiting for lifesaving therapies, that future is particularly urgent. Our singular focus at EE is to make it happen as fast as possible by serving as the hub of the final 10%—forging connections and providing critical funding, leadership, clinical development support, and strong, unwavering representation and advocacy. 

The energy, tenacity, and spirit of collaboration we experienced—from researchers and clinicians to advocates and community members—captured the heart of the CF community. We are profoundly grateful to everyone who came together in Seattle to celebrate breakthroughs, ignite bold ideas, and propel the next wave of life-changing innovation. It cannot come soon enough!

At EE, we remain relentless in our mission: accelerating research, supporting those in the final 10%, and pushing toward a day when CF is no longer a part of anyone’s story. The finish line is in sight, and we’re racing towards it with everything we’ve got.