Comprehensive Report on AIV-001: An Investigational Multi-Kinase Inhibitor Formulation for Dermatological Applications

1. Executive Summary

AIV-001 is an investigational therapeutic agent under development by AiViva Biopharma Inc. It represents a novel formulation of axitinib, a known multi-kinase inhibitor, combined with AiViva's proprietary delivery technology engineered for prolonged drug release following intradermal administration. The mechanism of action involves the inhibition of multiple kinases, including Vascular Endothelial Growth Factor Receptors (VEGFR), thereby targeting key pathways implicated in neovascularization, abnormal cell proliferation, inflammation, and fibrosis.

Currently, AIV-001 is primarily being investigated for dermatological applications, specifically the non-surgical treatment of nonmelanoma skin cancer, with a focus on basal cell carcinoma (BCC), and the management or prevention of dermal scarring and wound healing. Potential applicability in rosacea has also been suggested based on its mechanism. Completed Phase I/II clinical trials have provided preliminary evidence supporting its potential utility. In studies involving patients with BCC, AIV-001 demonstrated histological and clinical clearance of lesions with good local tolerability. In scar models, it showed a reduction in fibrosis formation. A significant regulatory milestone was achieved in late 2024 with the U.S. Food and Drug Administration (FDA) granting clearance for AIV-001 to be tested via intradermal injection in facial skin for BCC, based on safety data from previous non-facial studies. Despite these promising early results, AIV-001 remains an investigational product and has not yet received marketing approval from any regulatory agency.

2. AIV-001: Background and Formulation

2.1 Introduction to AIV-001

AIV-001 is an investigational drug candidate being developed by AiViva Biopharma Inc., a clinical-stage biotechnology company.[1] It is specifically identified as a novel formulation of axitinib.[1] Axitinib itself is an established small molecule drug, typically used in oncology settings, known for its potent kinase inhibitory activity. The development of AIV-001 thus represents a strategic repurposing effort, focusing on delivering this known active pharmaceutical ingredient via a new formulation and route of administration for novel therapeutic indications, primarily in dermatology.

2.2 Proprietary Delivery Technology

A key feature of AIV-001 is its formulation, which incorporates AiViva Biopharma's proprietary delivery technology.[1] This technology is explicitly designed to achieve prolonged drug release within the skin following intradermal injection.[4] The formulation exists as a suspension.[6] While AiViva possesses other named delivery platforms, such as the JEL® technology used for its ophthalmology candidate AIV007 [3], the specific proprietary name for the technology employed in AIV-001 is not disclosed in the available materials, only its functional characteristic of sustained local release.

The combination of intradermal injection and prolonged release aims to concentrate the therapeutic effect of axitinib directly within the target skin tissue layers, where conditions like basal cell carcinoma originate or where the processes of scar formation occur. Nonclinical studies have supported this concept, demonstrating a long residence time of the drug in the skin after a single treatment.[4] This sustained local drug presence is fundamental to the therapeutic hypothesis, potentially allowing for effective treatment with less frequent administrations compared to traditional topical or systemic therapies. Clinical trial protocols involving treatment intervals of several weeks further underscore this objective.[1] Maintaining therapeutic concentrations locally over extended periods, potentially with reduced dosing frequency, could enhance patient convenience and adherence, which are critical factors for managing chronic or recurrent dermatological conditions. Furthermore, localized delivery might improve the therapeutic window by minimizing systemic exposure and associated toxicities often seen with systemically administered kinase inhibitors.

2.3 Developer Context: AiViva Biopharma Inc.

AiViva Biopharma Inc. is described as a clinical-stage biotechnology company focusing on developing innovative focal therapies.[1] The company targets diseases characterized by neovascularization, abnormal cell proliferation, and fibrosis, primarily within the specialty therapeutic areas of dermatology, ophthalmology, urology, and oncology.[1] AiViva leverages its proprietary technologies to develop its pipeline candidates.[1] Besides AIV-001 (axitinib formulation), their pipeline includes AIV007, a formulation of the kinase inhibitor lenvatinib using their JEL® technology for periocular injection to treat retinal vascular diseases.[3]

This corporate focus provides context for the development of AIV-001. The company's strategy appears centered on applying known kinase inhibitors with established mechanisms to new therapeutic areas by utilizing proprietary local delivery systems. This approach potentially mitigates some early-stage development risks associated with entirely new molecular entities while creating novel therapeutic opportunities through formulation and delivery innovation. The targeting of fundamental pathological processes like angiogenesis and fibrosis provides a unifying theme across their different therapeutic areas and candidates.

3. Mechanism of Action (MoA)

3.1 Multi-Kinase and VEGFR Inhibition

AIV-001 functions as a multi-kinase inhibitor, leveraging the pharmacological activity of its active ingredient, axitinib.[4] Axitinib is characterized as a pan-tyrosine kinase inhibitor.[1] A primary and well-characterized target of axitinib, and thus AIV-001, is the Vascular Endothelial Growth Factor Receptor (VEGFR) family.[3] VEGFRs are critical mediators of angiogenesis, the process of forming new blood vessels. By inhibiting VEGFR signaling, AIV-001 is expected to limit the vascular supply required for tumor growth and survival, a key factor in treating cancers like BCC. This anti-angiogenic effect is also relevant to conditions like rosacea, where abnormal vascularity contributes to inflammation and clinical presentation.[4]

3.2 Targeted Biological Pathways

The inhibition of VEGFR and other relevant kinases by AIV-001 translates into effects on several biological pathways pertinent to its target indications:

• Neovascularization and Cell Proliferation: AIV-001 inhibits or reduces neovascularization (angiogenesis) and abnormal cell proliferation.[4] These effects are central to its potential anti-cancer activity in BCC, as tumors rely on both new blood vessel formation and uncontrolled cell division for growth and progression. The simultaneous targeting of both proliferation (via broader kinase inhibition) and angiogenesis (via VEGFR inhibition) may offer a more comprehensive anti-tumor effect compared to agents targeting only one pathway.
• Fibroplasia and Fibrosis: AIV-001 is designed to reduce fibroplasia, the formation of fibrous tissue, which occurs during wound healing and can lead to excessive scarring.[4] This anti-fibrotic activity forms the basis for its investigation in scar management.
• Inflammation: The mechanism is also suggested to limit inflammation, potentially contributing to its effects in both scarring and inflammatory dermatoses like rosacea.[4]

The combined anti-proliferative, anti-angiogenic, anti-inflammatory, and anti-fibrotic properties resulting from its multi-kinase inhibition profile suggest a potentially broad utility in dermatology. While current clinical focus is on BCC and scarring, the underlying mechanism supports the rationale for exploring other conditions where these pathways are dysregulated, such as rosacea, which was previously mentioned as a target indication.[4]

4. Nonclinical Findings

Preclinical evaluation of AIV-001 provided foundational support for its clinical development. In vivo nonclinical studies, specifically utilizing wound healing models, demonstrated that AIV-001 treatment resulted in reduced dermal neovascularization and fibroplasia.[4] These findings offered early evidence that the drug could modulate key processes involved in both angiogenesis (relevant to BCC and rosacea) and scar formation.

Crucially, these nonclinical studies also provided initial validation for AiViva's formulation strategy. They demonstrated that AIV-001 exhibited a long residence time in the skin following a single treatment application.[4] This observation supported the feasibility of the prolonged-release concept embedded in the proprietary delivery technology, suggesting that therapeutic drug levels could be maintained locally over time, potentially allowing for the less frequent dosing regimens subsequently employed in human clinical trials.

5. Clinical Development Program

5.1 Overview

AIV-001 has progressed through early-stage clinical development, with completed Phase I/II trials investigating its safety and efficacy in nonmelanoma skin cancer (specifically basal cell carcinoma) and in the context of incisional scarring and wound healing.[2] Collectively, three distinct clinical studies involving intradermal administration of AIV-001 have been completed, providing safety and preliminary efficacy data from a total of 67 subjects across both the BCC and scar management programs.[1]

5.2 Phase I/II Study in Nonmelanoma Skin Cancer (NCT04470726)

AiViva completed a Phase 1/2, multicenter, open-label clinical trial (NCT04470726) specifically evaluating AIV-001 in patients with BCC.[2] The study enrolled 26 subjects who had biopsy-confirmed superficial (sBCC), nodular (nBCC), or mixed BCC tumors measuring ≤20 mm, located on non-facial skin areas.[2] Participants were assigned to one of four ascending dose cohorts.[2] The treatment regimen involved administering AIV-001 via intradermal/intratumoral injection, with subjects receiving up to three treatments spaced approximately three weeks apart.[1]

The primary objectives included assessing safety, skin tolerability, and efficacy, measured by both clinical assessment and histological clearance of malignant basal cells within the treated lesions.[2] Efficacy results were promising: lesions treated with 10 mg doses (administered, for example, on Day 1 and Day 21) demonstrated high rates of both histological and clinical clearance.[3] Importantly, histological analysis revealed evidence of drug effect, including clearance of BCC margins and lesion debulking, across all dosing cohorts studied.[3] Overall, clinical and histological clearance was achieved in the cohort of 26 patients.[1] These findings suggest a dose-response relationship, a critical determination in early-phase trials that informs the selection of doses for subsequent, larger studies. The identification of an apparently effective dose regimen (10 mg) provides a foundation for designing potential Phase III trials.

Regarding safety, the trial reported excellent skin tolerability, with no clinically significant systemic or local (dermal) safety findings observed.[2] Systemic exposure to axitinib following intradermal administration was also assessed as part of the safety evaluation.[1] Based on these results, AIV-001 shows potential as a non-surgical, disease-modifying therapy capable of achieving high cure rates in both sBCC and nBCC subtypes.[3] This positions it as a potential alternative to standard surgical excision, particularly appealing for patients seeking to avoid surgery or those with lesions in cosmetically sensitive locations.

5.3 Clinical Evaluation in Scar Management/Wound Healing

In parallel with the BCC program, AiViva completed a Phase I/IIa clinical trial investigating AIV-001 for managing incisional scarring and wound healing.[4] Data from two trials utilizing scar models involved a total of 41 subjects.[1] The key finding from this program was the observation of reduced fibrosis formation following a single intradermal injection of AIV-001 administered over surgical incisional wounds.[1] This provides clinical support for the anti-fibrotic activity suggested by its mechanism of action and nonclinical studies, indicating potential utility in preventing or reducing post-surgical scars and possibly treating keloids.[5] Safety data gathered from these 41 subjects also contributed significantly to the overall safety database for AIV-001.[1]

The concurrent development for BCC and scar management may offer synergistic potential. A successful non-surgical BCC treatment like AIV-001 inherently avoids the scarring associated with surgical removal. Furthermore, its demonstrated anti-fibrotic effect could potentially enhance the cosmetic outcome of BCC treatment or serve as a standalone therapy for scar prevention or reduction following other types of skin surgery or injury.

5.4 Rosacea Indication Status

While the mechanism of action of AIV-001, particularly its VEGFR inhibition leading to reduced inflammation and vascularity, suggests potential relevance for treating rosacea [4], recent development updates indicate that there is currently no active clinical development reported for this indication as of December 2024.[6] Although previously mentioned as a potential application [7], it appears that clinical investigation for rosacea is not currently prioritized or may have been paused.

5.5 Summary of Clinical Trial Data

The table below summarizes the key details of the completed clinical trials for AIV-001 based on the available information.

Trial ID	Phase	Indication(s)	Formulation/Route	Status	Key Efficacy Findings	Key Safety Findings	No. of Subjects	Source Snippet(s)
NCT04470726	Phase I/II	Basal Cell Carcinoma (sBCC, nBCC, mixed; non-facial)	Axitinib suspension / Intradermal	Completed	High histological/clinical clearance with 10mg dose; All lesions showed drug effect	Excellent skin tolerability; No significant systemic/dermal safety issues; Systemic exposure assessed	26	1
N/A (Trial 1)	Phase I/IIa (implied)	Incisional Scarring / Wound Healing	Axitinib suspension / Intradermal	Completed (implied)	Reduced fibrosis formation	Contributed to overall safety database	Part of 41 total	1
N/A (Trial 2)	Phase I/IIa (implied)	Incisional Scarring / Wound Healing	Axitinib suspension / Intradermal	Completed (implied)	Reduced fibrosis formation	Contributed to overall safety database	Part of 41 total	1

6. Regulatory Status and Pathway

6.1 Current Regulatory Status

AIV-001 remains an investigational product candidate. It has not received marketing approval from the U.S. Food and Drug Administration (FDA) or any other global regulatory health authority.[1] Its use is currently restricted to clinical trial settings.

6.2 FDA Clearance for Facial Skin Testing

A significant regulatory advancement occurred in December 2024 when AiViva Biopharma announced receipt of FDA clearance to proceed with testing AIV-001 administered via intradermal injection in facial skin.[1] This clearance specifically pertains to the investigation of AIV-001 for treating superficial and nodular superficial basal cell carcinoma (sBCC and nBCC) lesions located on the face, neck, and scalp – areas considered cosmetically sensitive.[1]

This clearance was granted based on the FDA's review of a data package submitted by AiViva. This package included safety data related to non-facial skin tolerability, efficacy findings, and systemic drug exposure data derived from the 67 subjects who participated in the previously completed clinical trials for BCC and scar management on non-facial skin.[1] Obtaining this clearance represents a critical step, as interventions in facial skin often require heightened regulatory scrutiny due to cosmetic importance and potential visibility of adverse effects. Successfully demonstrating an acceptable safety profile in non-facial skin appears to have de-risked the progression to testing in facial areas.

6.3 Special Regulatory Designations

Based on the provided information, there is no indication that AIV-001 has received any special regulatory designations from the FDA, such as Orphan Drug Status or Fast Track designation.[1] The absence of Orphan Drug Status may relate to the high prevalence of basal cell carcinoma.

The FDA clearance for facial testing is a crucial enabler for AiViva's stated goal of developing AIV-001 as potentially the "first therapeutic developed for facial skin areas having sBCC or nBCC lesions".[1] Conducting pivotal trials in this specific patient population and location is necessary to substantiate claims for this intended use.

7. Therapeutic Potential and Future Outlook

7.1 Potential Clinical Role

AIV-001 holds potential as a novel, non-surgical treatment option for common forms of nonmelanoma skin cancer, specifically sBCC and nBCC.[2] Its development addresses a recognized need for alternatives to surgical excision, which remains a standard of care but can result in scarring and may be less desirable for lesions in cosmetically important areas like the face.[2] The positive preliminary efficacy (lesion clearance) and safety (good tolerability) data from the Phase I/II BCC trial support this potential.[2] Additionally, the observed anti-fibrotic effects in scar models suggest a separate or complementary role in scar management, potentially reducing scarring after surgery or injury.[1]

Given the high incidence of BCC, estimated at millions of cases annually in the U.S. alone [2], and the common patient preference for non-invasive treatments that minimize scarring, AIV-001 could capture a significant share of the BCC treatment market if its efficacy and safety are confirmed in larger, pivotal trials, particularly for facial lesions.

7.2 Competitive Advantages

The unique aspects of AIV-001 confer potential competitive advantages. The proprietary formulation enabling prolonged drug release via intradermal injection allows for targeted delivery directly to the affected skin tissue.[1] This localized approach may offer an improved safety profile compared to systemic administration of kinase inhibitors, by minimizing systemic exposure and associated toxicities. Furthermore, the potential for less frequent administration (e.g., weekly or less often, based on trial designs) compared to daily topical applications could improve patient convenience and adherence.[1]

7.3 Future Development and Outlook

Following the FDA clearance for facial skin testing, the logical next step for AiViva Biopharma is expected to be the initiation of larger clinical trials, likely Phase III studies, to definitively establish the efficacy and safety of AIV-001 for treating BCC, with a strong focus on facial lesions.[1] Continued development in scar management may also occur. The company has indicated an openness to exploring strategic partnerships for AIV-001.[2] The completion of Phase I/II studies with positive signals makes AIV-001 an potentially attractive asset for licensing or co-development, which could accelerate its progression through late-stage trials and towards potential commercialization by leveraging the resources and expertise of a larger pharmaceutical partner. AiViva believes its focal delivery approach is supported by a strong intellectual property position, which would be crucial in partnership negotiations and for long-term market exclusivity.[1]

8. Conclusion

AIV-001, a novel intradermal, prolonged-release formulation of the multi-kinase inhibitor axitinib developed by AiViva Biopharma, represents an innovative approach to treating dermatological conditions. Its mechanism, involving inhibition of VEGFR and other kinases, targets key pathways in neovascularization, cell proliferation, and fibrosis. Early-phase clinical trials have generated promising results, suggesting potential efficacy in achieving histological and clinical clearance of basal cell carcinoma lesions with good local tolerability, positioning it as a possible non-surgical treatment alternative. Furthermore, evidence of anti-fibrotic activity supports its potential use in scar management.

The recent FDA clearance to initiate clinical testing in facial skin for BCC marks a critical step forward, enabling investigation in cosmetically sensitive areas where non-surgical options are highly desirable. While AIV-001 holds significant therapeutic potential, it remains an investigational agent. Future clinical development, particularly pivotal trials evaluating its efficacy and safety in facial BCC, will be essential to fully define its clinical value and determine its place in dermatological practice. The company's strategy of leveraging proprietary delivery technology with a known kinase inhibitor exemplifies a focused approach to addressing unmet needs through formulation innovation.

Works cited

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