CFTR

The round secures funding for the company through 2026. Image credit: Shutterstock/OlekStock. Sionna Therapeutics has continued raising capital, closing a $182m Series C financing round to help advance additional cystic fibrosis candidates into clinical trials. The round, which was upsized and oversubscribed according to the US company, will see Sionna forge ahead with the clinical development of assets designed to stabilise the first nucleotide-binding domain (NBD1) in patients with cystic fibrosis. The round, which follows a $111m Series B round in 2022, secures the company’s cash runway through 2026. Sionna’s lead asset is SION-638 – an NBD1 stabiliser currently in Phase I trials. The first subject was dosed in January 2024, with the company stating that target exposure was achieved at all doses. Sionna said it will now advance two NBD1 stabilisers from its second series – SION-451 and SION-719. The two candidates are slated to join SION-638 in clinical trials in 2024, according to a 6 March press release. See Also: Amylyx considers scrapping ALS drug following Phase III flop Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene lead to cystic fibrosis. The gene codes for a transmembrane channel that produces mucus, which is usually thin and slippery in healthy individuals but thick and sticky in cystic fibrosis patients. One of the most common CFTR mutations—F508del—leads to NBD1 unfolding, which negatively affects CFTR function. Sionna says that its NBD1 stabilisers are designed to restore the function of the CFTR gene. Alongside its trio of NBD1 stabilisers, Sionna is investigating complementary mechanisms in the disease. The company’s CFTR intracellular loop 4 (ICL4) inhibitor SION-109 entered a Phase I trial in January 2024. The cystic fibrosis market is largely dominated by the Boston, Massachusetts-based Vertex Pharmaceuticals . Sionna stands to benefit from that expertise, with Vertex’s former vice president of clinical development for cystic fibrosis Charlotte McKee joining the company as chief medical officer, in 2022. Vertex’s Trifakta or Kaftrio (elexacaftor / tezacaftor / ivacaftor) drove much of the company’s revenue growth for 2023. The combo therapy, which is indicated for cystic fibrosis patients who have at least one F508del mutation, was originally US Food and Drug Administration-approved in 2019 and has since been granted label expansions . Trifakta saw sales of $8.9bn in 2023, up 16% from 2022. Vertex also has Symdeko (tezacaftor / ivacaftor), Orkambi (lumacaftor/ivacaftor), and Kalydeco (ivacaftor) as other FDA-approved therapies in the cystic fibrosis space. The company is also planning fast-track regulatory submissions for another triple therapy, involving vanzacaftor, by mid-2024 following positive Phase III results . Sionna’s CEO Mike Cloonan said: “This capital raise provides financial flexibility positioning us to execute our clinical development plan with funding through 2026 and multiple value-creating clinical readouts.”

- Company positioned to have four compounds in clinical trials in 2024 including three NBD1 stabilizers and one ICL4 modulator - - Edd Fleming, M.D., of Enavate Sciences joins company's Board of Directors - BOSTON, March 6, 2024 /PRNewswire/ -- Sionna Therapeutics, a clinical-stage life sciences company dedicated to developing highly effective and differentiated treatments for cystic fibrosis (CF), today announced the closing of a $182 million Series C financing to support the clinical development of first-in-class small molecules designed to fully restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein by stabilizing the first nucleotide-binding domain (NBD1). The Series C round, which was upsized and oversubscribed, was led by Enavate Sciences with additional new investors Viking Global Investors and Perceptive Advisors, as well as participation by all existing investors including RA Capital, OrbiMed, TPG's The Rise Fund, Atlas Venture, the Cystic Fibrosis Foundation, funds and accounts advised by T. Rowe Price Associates, Inc., and Q Healthcare Holdings, LLC., a wholly owned subsidiary of QIA. Sionna also announced today that Edd Fleming, M.D., Executive Vice President of Commercialization at Enavate Sciences, is joining its Board of Directors. "We have deep experience in CF and a sharp focus on advancing the development of novel small molecules targeting NBD1 and complementary modulators that enable the potential for full restoration of CFTR function for most people living with CF," said Mike Cloonan, President and Chief Executive Officer of Sionna. "We are encouraged by the strong interest and validation from the excellent investors in our upsized Series C financing. This capital raise provides financial flexibility positioning us to execute our clinical development plan with funding through 2026 and multiple value-creating clinical readouts. We are also pleased to welcome Dr. Fleming to our Board and look forward to insights from his more than 30 years of experience in the health care industry." CF is caused by mutations in the CFTR gene, which codes for an epithelial ion channel that is essential for producing healthy, freely flowing mucus in the airways, digestive system, and other organs. The most common mutation in CFTR, ΔF508, causes NBD1 to unfold at body temperature and severely impairs CFTR function. Sionna has presented preclinical data, including data from the clinically predictive human bronchial epithelial cell (CFHBE) model, that demonstrate its NBD1 stabilizers can restore ΔF508-CFTR maturation, trafficking, and function to wild-type levels when combined with complementary modulators. A Phase 1 clinical trial of its first clinical-stage NBD1 stabilizer, SION-638, has identified doses that are generally safe and well tolerated, and target exposure (based on the CFHBE assay) was achieved at all doses, with more time above target with increasing dose. Sionna has nominated two additional NBD1 stabilizers from its second series, SION-451 and SION-719, and plans to advance both compounds to clinical trials in 2024 pending results from ongoing Good Laboratory Practice (GLP) toxicology studies. In addition, the company is continuing to advance the development of compounds targeting complementary mechanisms including SION-109, which targets NBD1's interface with the CFTR intracellular loop 4 (ICL4) region; a Phase 1 clinical trial with SION-109 began in January 2024. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage life sciences company dedicated to developing highly effective and differentiated treatments for cystic fibrosis (CF) by normalizing the function of CFTR, the key protein associated with disease progression in CF. Building on over a decade of extensive research on the genetic mutations associated with CF and founded in 2019, Sionna is advancing a pipeline of small molecules engineered to correct the protein defects caused by ΔF508, the most common mutation that affects the CFTR protein. The company has a first-in-class portfolio of programs directly targeting correction of NBD1, the key and unique mechanism to enable full restoration of ΔF508-CFTR function, and complementary programs targeting ICL4 and TMD1. Sionna's pipeline has the potential to deliver best-in-class efficacy and reach previously unachievable levels of long-term benefit for people with CF. For information about Sionna visit . Media Contact Adam Daley Berry & Company Public Relations 212.253.8881 [email protected] Investor Contact [email protected] SOURCE Sionna Therapeutics

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 startsThe 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 2026The 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.