Tyrosine kinase inhibitor (TKI) with potential to treat VEGF-driven disorders such as wet AMD, diabetic macular edema and diabetic retinopathy

High potency and pan-VEGF attributes of TKI axitinib

Targeted delivery via SCS Microinjector®

Enhanced durability via small molecule suspension

Axitinib is a highly potent tyrosine kinase inhibitor (TKI) that achieves pan-VEGF inhibition through receptor blockade. We believe that pan-VEGF inhibition is potentially more efficacious than current approaches. Axitinib acts at a different level of the angiogenesis cascade, directly inhibiting VEGF receptors-1, -2, and -3 with high specificity. We believe this broad VEGF blockade may have efficacy advantages over existing retinal therapies and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Compared to other TKIs, axitinib is 10x more potent, has better ocular cell biocompatibility, and is more effective for experimental corneal neovascularization.

Current wet AMD therapy has a ceiling of efficacy as increased dosage or more intense regimens yield limited or no additional visual benefit and are associated with a significant treatment burden for patients. This treatment burden is further highlighted by recent large “real-world” retrospective studies of wet AMD which underscore the difficulty in adhering to regimens. These real-world studies demonstrate that patients are undertreated, receiving only 6 to 7 injections per year on average, resulting in mean improvement of only one to three letters in visual acuity after one year of treatment. In contrast, CLS-AX provides targeted high levels to affected choroid-retina to leverage the TKI for potential efficacy benefits.

CLS-AX (axitinib injectable suspension) is a proprietary suspension of axitinib delivered via our SCS Microinjector, and is being developed as a long-acting therapy for the treatment of wet AMD. Delivery via our SCS Microinjector compartmentalizes drug away from the vitreous and anterior chamber. This delivery behind the retina and outside the visual field eliminates symptomatic floaters and other certain side effects from other procedures. In addition, the in-office procedure can be easily adopted in current clinical practice.

Suprachoroidal administration of axitinib has the potential to achieve prolonged duration and targeted delivery to affected tissue layers. This provides meaningful durability after each injection, thus potentially reducing the burden on patients from current monthly injections.

Suprachoroidal Injection of CLS-AX Provides Greater Targeted Delivery

Abbreviations: SCS: Suprachoroidal Space | RPE: Retinal pigment epithelium

CLS-AX Phase 2b Clinical Trial in Wet AMD

  • Design: Randomized, double-masked, parallel-group, active-controlled, multi-center, clinical trial comparing CLS-AX suprachoroidal injection and aflibercept intravitreal injection over 36 weeks.
  • Participants: 60 total participants with 2:1 randomization; treatment experienced with reading center confirmation of persistent active disease.
  • Multiple Dosing Requirement: Every participant in the CLS-AX arm re-dosed with CLS-AX at least once

  • Primary outcome measure: Mean change in BCVA from Baseline to Week 36.

  • Secondary outcome measures: changes in visual function and ocular anatomy, need for supplemental treatment, treatment burden as measured by total injections over trial duration.

Trial Objectives

Evaluate safety, efficacy & duration of CLS-AX in participants with wet AMD

Number of Participants

60 Total with 2:1 Randomization*
(40 in CLS-AX arm & 20 in aflibercept arm)

Additional information on the ODYSSEY Phase 2b trial can be found on ClinicalTrials.gov NCT05891548.

CLS-AX Clinical Trial Results

References:

Medscape: F Ryan Prall, MD, et al Assistant Professor of Ophthalmology, Indiana University School of Medicine | Pennington, Katie L and DeAngelis, Margaret M Eye and Vision, Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors, Dec 22, 2016. | Cabral T et al. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018 January; 2(1): 31–37. doi:10.1016/j.oret.2017.04.004. | Lieu et al. The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer. PLoS ONE 8(10): e77117. | Ciulla TA et al. Ophthalmology Retina. 2019 May 25. pii: S2468-6530(19)30280-5. | Viral S. Kansara, Leroy W. Muya, Thomas A. Ciulla; Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits. Trans. Vis. Sci. Tech. 2021;10(7):19.