Transforming Growth Factor
THE ROLE OF
TGF-BETA
Transforming growth factor beta (TGF-β) plays an important role in key biological processes such as cell proliferation, cell differentiation, immune response and tissue modeling. Because TGF-β is chronically elevated in many diseases, including ophthalmic and fibrotic diseases and cancer, and involved in their pathophysiology, it is an extremely versatile drug target throughout the body.
In ophthalmology, certain gene variants affecting the TGF-β pathway are expected to lead to a higher risk for patients to suffer from more severe forms AMD during their lifetime, which suggests that TGF-beta might contribute to disease progression.
In oncology, TGF-beta is postulated to have both a tumor suppressor role and can act as a pro-oncogenic factor depending on disease progression. Because of this dual role, members of the TGF-beta signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis, as well as molecular targets for prevention and treatment of cancer and metastasis.
Pipeline
Isarna has established a broad portfolio of next-generation first- and best-in-class antisense oligonucleotides blocking three key TGF-β variants with therapeutic potential across a range of indications. In ophthalmological indications, our compounds are clearly differentiated from the currently marketed anti-VEGF compounds such as Eylea and Lucentis and offer the potential for improved efficacy. Isarnahas started Phase 2a development in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). The approach has near-term upside potential through expanding the program into other key ophthalmology indications i.e., dry forms of age-related macular degeneration.
Indication /
Target
Research
Preclinical
Phase 1
Phase 2A
Phase 2B/3
Ophthalmology (TGF-B2)
nAMD/DME
dryAMD
Glaucoma Surgery
FIBROSIS/NASH
TGF-B1
ONCOLOGY
TGF-B2
TGF-B1
TGF-B3
TGF-B4
Clinical Trials
ISTH0036 is a locked nucleic acid-modified antisense oligonucleotide selectively targeting the messenger RNA (mRNA) of TGF-β2. Preclinical studies have demonstrated that ISTH0036 is highly potent and shows selective target engagement (TGF-β2 mRNA and protein downregulation) consistent with long-lasting tissue uptake and pharmacodynamic effects.
Isarna and its collaboration partners presented Phase I safety and efficacy data in advanced-stage glaucoma patients undergoing trabeculectomy for ISTH0036 at The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in 2017. Overall, the treatment was safe and well tolerated at all dose levels and a trend in post-operative intraocular pressure (IOP) analysis provided preliminary evidence for a beneficial effect of ISTH0036 at the two highest dose levels evaluated.
Based on the promising clinical and preclinical data package obtained, Isarna started a Phase 2a clinical trial in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). More information will be provided in due time on our website and on www.clinicaltrials.gov