Dermatology
Addressing Skin Conditions That Are Underserved
Nonmelanoma Skin Cancer
In the U.S. alone, an estimated 3.6 million cases are diagnosed each year with basal cell carcinoma (BCC). Basal cell carcinoma (BCC) is a type of skin cancer that often develops on areas of skin exposed to the sun, such as the face. This is the most common form of skin cancer and the most frequently occurring form of all cancers. AiViva is targeting two of the four main clinical subtypes of BCC: nodular (nBCC) and superficial (sBCC).
Positive Results of AIV001 Intradermal Injection as a Nonsurgical Option for Treatment of Nonmelanoma Skin Cancer
Nonmelanoma skin cancers are the most diagnosed cancer with 80% of lesions of basal cell carcinoma (BCC) form1-3 with highest occurrence in facial skin4. Primary BCC treatment is surgical removal, thus an effective nonsurgical treatment option would benefit patients that are not willing or not good surgical candidates, particularly in cosmetic sensitive skin areas.
AIV001(axitinib) is a potent vascular endothelial growth factor (VEGF) receptor inhibitor formulated for intradermal injection with prolonged skin residence. A first-in-patient phase 2a study (NCT 04470726) was completed in four dosing cohorts to determine systemic and dermal safety and BCC clearance rates. A total of 26 subjects with 28 biopsy-confirmed ≤20 mm superficial (sBCC) and/or nodular (nBCC) lesions in non-facial skin were enrolled at four U.S. sites.
No clinically significant systemic or dermal safety findings were reported. All treated lesions showed evidence of drug effect by histology with clear BCC margins. Lesions receiving 10 mg treatments (e.g., Day 1 & 21) provided results in high histological5 and clinical clearance rate. Drug effects assessed by histological biomarkers5 and evidence of lesion debulking, were reported in all four dosing cohorts.
AIV001 demonstrated potential to be the first disease-modifying therapy with a high cure rate in both sBCC and nBCC lesions with excellent skin tolerability. Also, the safety database from three independent dermal trials using intradermal AIV001 injections in non-facial skin supports the future testing in facial skin. This simple injection administered by physicians will provide an option for patients seeking nonsurgical methods for treating BCC lesions.
Objectives
- In a first-in-patient nonmelanoma skin (NMSC) cancer trial, optimize delivery of an intradermal/intratumoral injection to biopsied confirmed basal cell carcinoma (BCC) lesions of ≤20 mm.
- Evaluate the systemic and dermal safety of up to three AIV001 treatments over a 21-day treatment interval
- Assess the effectiveness of AIV001 ascending doses on histological and clinical clearance rates and histological cellular responses .
References
(1) Cameron, M.C. et al. (2019) ‘Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histological subtypes; and disease associations.’, Journal of the American Academy of Dermatology, 80(2), pp. 303–317. (2) Ciążyńska, M. et al. (2021) ‘The incidence and clinical analysis of non-melanoma skin cancer’, Scientific Reports, 11(1), pp. 1–10. (3) Ciuciulete, A.-R. et al. (2022) ‘Non-Melanoma Skin Cancer: Statistical Associations between Clinical Parameters.’, Current health sciences journal, 48(1), pp. 110–115. (4) Waldman, R.A., Grant-Kels J. (2022) Dermatology for the Primary Care Provider. (5) Cockerell Dermatopathology Laboratory performed biopsy assessments and histological clearance evaluations.
AIV001-C01 NCT 04470726; AIV001 is an investigational product candidate currently in clinical development in the United States. The efficacy and safety profiles have not been established, and they have not been approved for marketing by the Food and Drug Administration.
Scar Prevention
An estimated 100 million people in the developed world form scars following surgery (1). In the U.S. there are approximately eight million surgical procedures performed annually wherein scarring is a concern (2). Scarring results from abnormal deposition and organization of collagen, with no difference between normal and scarred skin in composition of dermal tissue. The pathogenesis of scar formation is poorly understood. Scarring can have negative physical, aesthetic, and psychological effects if left untreated. There are no approved drugs for scar prevention following surgery; treatments are limited to pressure dressings, silicone sheeting/gels, steri-strips, and steroid injections.
Rosacea
Rosacea is a common skin condition that affects over 16 million individuals in the U.S. and, according to some estimates, hundreds of millions of people worldwide (3). Rosacea is a chronic relapsing inflammatory skin disease primarily affecting the face. Rosacea comprises uncontrolled vasodilation, inflammation, and later fibrosis associated with glandular hyperplasia which presents as persistent erythema. This disease is thought to be under treated, as it’s often mischaracterized as acne. Current treatments consist of oral and topical medications that are taken or administered daily with limited efficacy.
AiViva is developing AIV001 to address the negative impacts that scarring and rosacea can have on patients.
1. Sund, 2000. 2. American Society of Plastic Surgeons. 3. Berg M, Liden S. An epidemiological study of rosacea. Acta Dermato-Venereologica. 1989;69:419-423.
Ophthalmology
Addressing Unmet Needs in Neovascular AMD
Neovascular Age-Related Macular Degeneration (nAMD)
Neovascular age-related macular degeneration (nAMD) is a chronic eye disorder that causes blurred vision or a blind spot in the visual field. It is generally caused by abnormal blood vessels that leak fluid or blood into the macula, the part of the retina responsible for central vision. Neovascular AMD affects 11 million people in the United States and is the leading cause of vision loss in people age 50 and older. The number of people with nAMD is expected to double as the population continues to age (1). The mainstay treatment modality for nAMD involves intravitreal (IVT) injectable anti-VEGF therapies, with the leading drugs accounting for approximately $8 billion in sales in 2018 (2). Anti-VEGF therapies have shown treatment success, however, the disadvantages of current treatment therapies include frequent visits to the Ophthalmologist for intravitreal injections, development of tolerance, and development of subretinal scarring (3, 4).
1. Pennington, K., et al. Epidemiology of age-related macular degeneration (AMD) 2. IMS Revenue Data & SEC filings 3. Daniel, E. et al. Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trial, 2014. 4. Daniel, E. et al. Development and Course of Scars in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT), 2018.
Diabetic Macular Edema (DME)
DME is manifested as retinal thickening caused by the accumulation of intraretinal fluid, primarily in the inner and outer plexiform layers. It is believed to be a result of hyperpermeability of the retinal vasculature. DME can be present with any level of diabetic retinopathy.
In USA: The WHO (World Health Organization) estimates 15 million DME half undiagnosed and 50% of 8 million without eye care, 25-30% risk of vision loss from CSME. International, WHO estimates more than 150 million patients with diabetes worldwide. However, the absolute prevalence of DME might be increasing due to the overall increased prevalence of diabetes in industrialized nations. It is expected that the incidence of DME will decrease as excellent metabolic control is increasingly embraced as a therapeutic goal by patients and health care workers.
AiViva is developing AIV007 (lenvatinib) a broad spectrum-tyrosine kinase inhibitor, targeting critical pathways involved in angiogenesis, inflammation, and fibrosis. AIV007 was formulated in a JEL® technology for periocular injection and durability and being developed for patients with various retinal vascular diseases.
1. Albert and Jakobiec’s Principles and Practice of ophthalmology. Third edition, second volume. Canada: SAUNDERS ELSEVIER; 2008. pp. 1793–1996. 2. Pr Gabriel Coscas. Oedemes maculaires Aspects cliniques et therapeutiques.Spain: Springer Science & Business Media; 2011. Sep 15, pp. 110–196.