Cystic fibrosis contender Sionna secures $182M for clinical push

2024-03-06

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Sionna Therapeutics on Wednesday announced that it raised $182 million in an oversubscribed Series C financing to fuel development of new cystic fibrosis (CF) treatments, a space dominated by Vertex Pharmaceuticals at the moment.

"There is room for improvement over existing therapies because we have not yet achieved fully normalised function of the CFTR protein for the majority of people living with cystic fibrosis," CEO Mike Cloonan told FirstWord. "Our laser focus on cystic fibrosis has enabled us to progress potentially four compounds into the clinic this year including three NBD1 modulators."

At the forefront of its efforts are small molecules designed to stabilise the first nucleotide-binding domain (NBD1) of the CFTR protein, alleviating the underlying cause of CF. The most common mutation, referred to as ΔF508, causes NBD1 to unfold at body temperature and severely impairs CFTR function. Sionna notes that NBD1 is a well-known and researched target, but has been considered undruggable until now.

2024 study starts

The company's programmes directly target the correction of NBD1 to enable full restoration of ΔF508-CFTR function, although it is also working on compounds that target complementary mechanisms – ICL4 and TMD1 – two other key regions of the CFTR protein.

Its lead NBD1 stabiliser, SION-638, has already shown promise in a Phase I trial of healthy volunteers, identifying safe and well-tolerated doses that achieved target exposure levels. The study is expected to complete in the first half. Sionna's arsenal includes two additional NBD1 stabilisers – SION-451 and SION-719 – that are poised to enter Phase I this year.

"Our portfolio approach will allow us to select the best compounds for Phase IIa proof-of-concept trials, based on Phase 1 data," Cloonan said.

The company is also advancing SION-109, a compound targeting NBD1's interface with the CFTR intracellular loop 4 (ICL4) region, which entered early-stage testing this past January. Its TMD1-targeting compound SION‑676 is currently in IND-enabling studies.

Preclinical data, including results from a human cell model, suggest its NBD1 stabilisers could bring ΔF508-CFTR maturation, trafficking, and function back to normal levels when paired with complementary modulators.

Funding fuel through 2026

The upsized round was led by Enavate Sciences, with new contributors Viking Global Investors and Perceptive Advisors and existing backers such as RA Capital, OrbiMed, TPG's The Rise Fund, Atlas Venture and the Cystic Fibrosis Foundation also participating. "This capital raise provides financial flexibility positioning us to execute our clinical development plan with funding through 2026," Cloonan said.

When it comes to CFTR protein restoration, Vertex currently leads the way with four products already on the market all centred on the potentiator Kalydeco (ivacaftor). It has another programme in Phase III evaluating a combination of the CFTR correctors vanzacaftor (VX-121) and tezacaftor together with deutivacaftor (VX-561), an altered form of ivacaftor, with plans to file for US approval of the so-called "vanza triple" by mid-year.

Vertex is also working on the inhaled mRNA therapy VX-522 that would be delivered to the lungs by lipid nanoparticles to treat approximately 5000 patients with CF who do not make any CFTR protein that responds to a CFTR modulator therapy. The candidate is currently in Phase I.

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