丨Medicine Hunter Club Research Team
July 16, 2024, a clinical-stage life sciences company dedicated to developing efficient and differentiated treatments for cystic fibrosis (CF)Sionna Sionna Therapeutics, Inc. announced that it has reached a collaboration agreement withAbbVieReach a licensing agreement to obtain global exclusive rights for the development and commercialization of multiple clinical-stage compounds.
According to the terms of the agreement, Sionna will be responsible forgalicaftor (ABBV-2222)、navocaftor (ABBV-3067)AndABBV-2851all development. Sionna will prioritize advancing one of AbbVie's compounds and SION-109 in collaboration withThe First Nucleotide-Binding Domain (NBD1) StabilizerThePotential Dual Combination Regimen。
Financial terms were not disclosed, AbbVie will receive aAdvance PaymentAnd Sionna'sShares, and is eligible for later development and commercialMilestoneAndRoyalty。
Sionna CorrectCystic FibrosisThe Market is Watching Closely
Sionna Therapeutics, Inc. was founded in 2019, headquartered in Massachusetts, USA, and incubated by the investment firm RA Capital Management. It is a clinical-stage biopharmaceutical company focused on developing novel small-molecule therapies for the treatment of cystic fibrosis.March 6, 2024Sionna Announced the completion of a $182 million Series C financing round, which will be used to advance its clinical development programs and provide financial support for the company through 2026.Sionna Therapeutics, Inc. has raised a total of $332 million in funding since its inception.
Sionna Therapeutics Financing HistorySionnaNovel small molecule therapies targeting the most common genetic mutation ΔF508 affecting cystic fibrosis (CF) patients are under development, aiming to normalize CFTR function.CThe most common mutation ΔF508 in the CFTR protein leads to an abnormality in the nucleotide-binding domain 1 (NBD1) of the CFTR protein, severely disrupting CFTR protein function.
Sionna has developed a series of small molecule drugs aimed at correcting the protein defect caused by ΔF508.These small molecule drugs mainly help achieve this by stabilizing the NBD1 of CFTR protein.CFTR ProteinFunctional recovery.
SION‑638 Is aNBD1 Stabilizer，Positive preclinical trial results show that data from the human bronchial epithelial cell (CFHBE) model indicate its combination with complementary modulators can restore various functions of ΔF508-CFTR protein to wild-type protein levels. SION‑638 has already established a safe and well-tolerated dosing regimen in Phase 1 clinical trials, with all doses achieving target exposure levels based on CFHBE assays. Based on these positive results, the company stated that SION‑638 is expected to provide best-in-class efficacy for cystic fibrosis patients and achieve long-term efficacy levels previously unattainable.
In addition, Sionna has also developed otherTwo typesNBD1 Stabilizer, respectively SION-719And SION-451Drug pipeline, and plans to advance these two pipelines to the clinical trial stage in 2024. Toxicology studies are currently underway.The deal with AbbVie provides Sionna with treatmentCystic FibrosisThe drug components.In clinical studies conducted by AbbVie, ABBV-2222 and ABBV-3067 were generally safe and well-tolerated. In Phase 2 clinical trials, the combination of ABBV-2222 and ABBV-3067 demonstrated clinical efficacy, including an increase in predicted percent forced expiratory volume in one second (ppFEV1) and a reduction in sweat chloride (SwCl) levels, comparable to approved dual corrector combinations. In preclinical trials conducted by Sionna, including cystic fibrosis human bronchial epithelial (CFHBE) assays, combinations of Sionna’s NBD1 stabilizers with licensed AbbVie potentiators showed potential efficacy superior to current standard of care, and some combinations have the potential to fully correct ΔF508 CFTR and achieve wild-type CFTR functional levels.
GlobalCystic Fibrosis Market -- Vertex Dominates
Cystic Fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CFTR gene, classified as a monogenic hereditary disease. It mainly affects respiratory and gastrointestinal functions, with patients typically presenting with chronic obstructive pulmonary disease, pancreatic exocrine insufficiency, and abnormally elevated sweat electrolytes.The cystic fibrosis transmembrane conductance regulator (CFTR) encoded by the CFTR gene is a membrane protein in vertebrates. It functions in nutrient absorption, toxin excretion, and mediating intercellular communication between eukaryotic and bacterial cells. Additionally, the CFTR protein is expressed in mucus-secreting glands and is crucial for producing healthy, free-flowing mucus in the respiratory, digestive, and other systems.
Since the discovery of the CFTR gene mutation responsible for cystic fibrosis, researchers have made significant clinical progress. However, the ultimate goal of cystic fibrosis drug development—fully restoring the function of the critical disease-causing protein CFTR—remains challenging.Regarding the treatment of cystic fibrosis, several global pharmaceutical giants have actively positioned themselves, includingVertex Pharmaceuticals、AbbVie, Boehringer Ingelheim, Pfizer, Merck, Translate Bio, and Proteostasis Therapeutics, among others. However, the R&D results have been disappointing. Proteostasis Therapeutics, which focuses on the development of cystic fibrosis treatments, has failed to produce a drug combination superior to Vertex's therapies. Translate Bio's messenger RNA-based approach has also been disappointing, as have PTC Therapeutics' prospective drugs. In terms of pipeline quantity, R&D progress, and sales,Currently, the cystic fibrosis market is dominated by Vertex Pharmaceuticals., OwnsArticle 16The pipeline of treatments for cystic fibrosis, where7 ProductsDrug Approval for Marketing,1 ProductDrug application for marketing,7 ProductsOne drug has entered clinical trials, and one is in the preclinical stage.Vertex Cystic Fibrosis Treatment Drug Research Progress
According to Vertex's 2023 performance, the total annual product revenue was $9.87 billion, with the main income coming from the cystic fibrosis treatment sector. The CF triple combination therapy TRIKAFTA (ivacaftor/tezacaftor/elexacaftor)/KAFTRIO (Elexacaftor/Tezacaftor/Ivacaftor) reached $8.948 billion, an increase of $1.3 billion year-over-year. Other cystic fibrosis drugs generated sales of $925 million, a decrease of approximately $320 million year-over-year.
According to the industry report titled "World Preview 2024 – Pharma’s Growth Boost" released by the industry media Evaluate,Vertex's new triple combination product Vanzacaftor/tezacaftor/deutivacaftor has been included in the 2024 Top 10 Potential Blockbuster Pipeline list and will become a new mainstay for Vertex's sales in the future.Vanzacaftor/Tezacaftor/Deutivacaftor Combination Therapy Shows Positive Results in Phase 2 Clinical Trial for Cystic Fibrosis TreatmentIn this triple combination therapy, vanzacaftor and tezacaftor aim to increase the number of mature proteins on the cell surface by targeting processing and trafficking defects of the CFTR protein. Deutivacaftor is designed to keep the CFTR protein at the cell surface open for a longer duration, improving the movement of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.Compared with the older product TRIKAFTA, the new product shows improvements in both efficacy and treatment scope. It retains the corrector component (tezacaftor) of TRIKAFTA, replaces the potentiator component with an upgraded version of deuterated ivacaftor (i.e., VX-561), and combines it with VX-121. This new combination may allow patients to take the medication just once a day, significantly enhancing the convenience of use.According to Evaluate's forecast, by 2030, the sales of the new triple combination will reach $7.7 billion, with a net present value of $30.4 billion.Why AbbVie PacksSellCystic FibrosisPipeline?
AbbVie has always shown great favor towards the cystic fibrosis market.In 2013, AbbVie joined hands with Galapagos, officially entering the CF field, and willGlobally co-develop and commercialize novel oral therapies for cystic fibrosis,Total transaction amount exceeds 200 million US dollars.At that time, Vertex's newly developed CF drug, ivacaftor, had successfully been launched on the market. It was the first therapy targeting the root cause of CF. Facing a formidable opponent, AbbVie did not back down and hoped to iterate through combination therapy.In 2016, AbbVie deepened its collaboration with Galapagos on the development of the CF triple combination therapy.In 2018, despite two sets of unsatisfactory clinical data, AbbVie still acquired Galapagos' CF pipeline, including ABBV-119, for a $45 million upfront payment.The application of ABBV-119 in combination with ABBV-3067 and ABBV-2222 has become a key focus of AbbVie's exploration. However, the concept validation revealed that the addition of ABBV-119,Did not achieve enhanced efficacy on the original dual-drug regimen.Even if ABBV-119 is replaced with ABBV-576, which has a completely new structure,Nor has it achieved the desired effect.。So far, AbbVie inCystic FibrosisAll attempts in the field have ended in failure,In 2023, AbbVie terminated the development of the CF project.Summary
Perhaps still holding expectations for the CF field，In this collaboration,AbbVie Agrees toSionnaProviding equity investment as part of licensing agreements for multiple candidate drugs.WithAbbVie's Full Support，Sionna Gains More Leverage in Head-to-Head Competition with Vertex.In currently available CF therapies, approximately two-thirds of patients still do not achieve normal CFTR function. This time, in collaboration withAbbVie's collaboration will provide supportSionnaSignificantly expand and accelerate the complementary modulator pipeline associated with NBD1, and create multiple options for a potentially transformative combination to fully normalize CFTR function.SionnaNew combinations of potential modulators developed based on stable NBD1, with NBD1 modulators combined with three licensed schemes from AbbVie, show greater efficacy potential than standard treatments.
Source:
PharmaCube: AbbVie's Advances and RetreatsSheng Hui: Targeting Vertex, Sionna Bets $182 Million on New "Cystic Fibrosis" Therapy, Plans to Advance 4 Pipelines to Clinical Trials This YearCompany Official Website
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