Conferência Norte-Americana de FC 2019: Avanços para mutações Nonsense da FC

Emily’s Entourage (EE) attended the North American Cystic Fibrosis Conference (NACFC) in Nashville, TN from October 31 to November 2, 2019. This conference, held annually by the Cystic Fibrosis Foundation (CFF), brought together over 5,000 Cystic Fibrosis (CF) clinicians, researchers, and caregivers in one space to discuss the latest CF research, care, and drug development. The conference focused on exchanging ideas to improve the health and wellness of people with CF.

The 33rd NACFC came at a particularly integral moment in CF history. On October 21, 2019, the Food and Drug Administration announced its approval of the highly-anticipated triple combination therapy, TRIKAFTA™, developed by Vertex Pharmaceuticals, for 90% of the CF population ages 12 and older who have at least one copy of the most common CF mutation, F508del. TRIKAFTA™ is a combination of three CFTR modulators (a “triple combination” therapy). Together, the three drugs increased mean lung function by 13.8% in the Phase 3 trial, exceeding all expectations and restoring lung function to a level many in the CF community had not experienced in decades.

The relevance and urgency of EE’s laser-focused mission to speed breakthroughs and a cure for nonsense mutations of CF became more apparent than ever in discussions throughout the conference. The limits of TRIKAFTA™ were a focal point of discussion and reinforced the pressing need to develop therapies for those in the outlying 10% that would not benefit from TRIKAFTA™, including those with two nonsense mutations. Multiple sessions presented research to accelerate breakthroughs for those without life-saving treatments available or in late-stage clinical trials.

The following therapies presented at NACFC have direct relevance to nonsense mutations of CF:

• Eloxx Pharmaceuticals presented the “readthrough” agent ELX-02, a small molecule therapy in phase 2 clinical trials for individuals with nonsense mutations of CF. Those with nonsense mutations of CF do not produce a full-length, fully functional CFTR protein, which inhibits the body’s ability to regulate chloride within the cell. The way ELX-02 works is by promoting the production of the full-length CFTR protein to partially restore CFTR function in disease-affected organs, such as the lungs. ELX-02 showed compelling efficacy in model systems that supported its progression to clinical trials. Phase 1 clinical trials successfully focused on safety and current phase 2 clinical trials focus on CF caused specifically caused by the G542X nonsense mutation.
• Traduzir biografia presented their messenger RNA-based therapeutic approach for CF, MRT5005, which is in phase 1/2 clinical trials. Messenger RNAs (mRNAs) serve as intermediaries that relay gene-encoded information to cells that generate proteins. MRT5005 uses therapeutic mRNAs capable of producing the normal CFTR protein to replace afflicted mRNAs containing mutations. Of particular note, Translate Bio’s approach is mutation-agnostic approach, meaning it could benefit everyone with CF regardless of their specific genetic mutation.
• Enterprise Therapeutics presented the potentiator TMEM16A, which is in preclinical development with hope to progress into phase 1 clinical trials soon. TMEM16A acts as an alternative chloride channel in the airways and could compensate for lost CFTR activity, restoring normal lung function and clearance of bacterial infections. Similar to Translate Bio’s approach, this therapy is mutation-agnostic and could benefit everyone with CF regardless of their mutation.

Complementing the informative and inspiring sessions at NACFC, EE was thrilled to hold its 4th Annual, invitation-only NACFC Cocktail Reception for over 90 CF scientists, researchers, and caregivers on November 1. This event served as a venue for EE to share its annual progress, learn about researchers’ progress, and most of all, celebrate and honor the EE scientific community. The event was attended by top researchers, clinicians, nearly all of the major CF biotech companies, and CFF leadership, reflecting their shared commitment to our mission.

EE is grateful to the entire CF research community for its persistence in speeding the development of therapies for the final 10%, including those with nonsense mutations of CF. Their determination was demonstrated and strongly felt at NACFC. EE remains committed to facilitating scientific collaboration, research and drug development to make these therapeutics a reality as soon as possible.