Sionna revitalizes AbbVie's discarded CF compounds

Sionna Therapeutics has taken significant strides in the cystic fibrosis (CF) therapeutic landscape by acquiring exclusive global rights to various CF assets from AbbVie, a pharmaceutical company that had previously abandoned its CF program due to unsatisfactory clinical outcomes. Specific financial details of the agreement remain undisclosed, although it includes an upfront payment to AbbVie, along with potential development and commercial milestone payments, and royalties. Additionally, AbbVie has made an equity investment in Sionna Therapeutics, which recently raised $182 million during an oversubscribed Series C funding round.

The agreement specifically involves several compounds: ABBV-2222 (galicaftor) and ABBV-3067 (navocaftor), both of which have successfully completed Phase II trials, and ABBV-2851, which is currently in Phase I development. ABBV-2222 and ABBV-2851 function as TMD1-directed correctors, while ABBV-3067 serves as a CFTR potentiator. AbbVie's decision to halt its CF program was influenced by the failure of a triple combination therapy in a proof-of-concept study. This combination therapy included the C2 corrector ABBV-576 along with a backbone of ABBV-2222 and ABBV-3067, which did not meet the expected efficacy criteria.

Sionna Therapeutics, however, views these compounds as promising when paired with its proprietary NBD1 stabilizers. The company points to preclinical assays indicating that such combinations could unlock new treatment potentials. "Our strategy is to build a CF franchise anchored on our novel correctors that stabilize the NBD1 of the CFTR protein," stated Sionna's CEO, Mike Cloonan. The company's approach involves pairing its NBD1 stabilizers with either AbbVie's compounds or its own ICL4-directed corrector, SION-109, to develop more effective dual combinations.

The preclinical studies have shown encouraging results for these pairings, with some combinations demonstrating the potential for superior efficacy compared to existing treatments. Notably, some combinations appear capable of fully correcting the ΔF508 CFTR and achieving wild type levels of CFTR function, which represents a significant therapeutic advancement.

Sionna Therapeutics has outlined an ambitious roadmap for its development programs. The company plans to complete a Phase I trial of SION-109 in the latter half of the year. Additionally, Phase I studies for two NBD1 stabilizers, SION-451 and SION-719, are slated to begin this year. Among its portfolio, Sionna's most advanced NBD1 corrector, SION-638, is set to enter Phase II trials soon. Moreover, the company is progressing with the development of another TMD1-directed corrector, SION-676.

By reviving AbbVie's previously discarded compounds and leveraging its own proprietary technologies, Sionna Therapeutics aims to expand and enhance the treatment options available for CF patients. Their innovative approach and strategic acquisitions could potentially lead to breakthroughs that may offer superior efficacy over current CF therapies. The company's concerted effort to advance multiple compounds through clinical trials underscores its commitment to addressing the unmet needs within the CF community.