Exclusive License Agreement Term Sheet between AAVnerGene Inc. and Klotho Neurosciences, Inc.
AAVnerGene Inc. and Klotho Neurosciences, Inc. have agreed to a term sheet for an exclusive global license allowing Klotho to use AAVnerGene’s AAVone platform technology to develop, manufacture, and commercialize gene therapy products targeting specific neurological diseases. The agreement outlines fees, deliverables, and milestone payments for three clinical programs, with royalties on future sales. The license is contingent on patent approval, and a definitive agreement will be finalized later. Both parties signed the agreement on July 16, 2025.
Exhibit 4.1
AAVone License - Terms of Agreement
Between AAVnerGene Inc. and Klotho Neurosciences, Inc. (“KLTO”)
The License Terms of Agreement and collaboration (the “Agreement”) sets forth the terms of an exclusive license and the activities and deliverables associated with a license for KLTO to utilize the AAVone and potentially the AAVShD platform technologies developed by AAVnerGene. The primary activities are associated with a deliverable related to a product candidate called KLTO-202 which targets amyotrophic lateral sclerosis and other rare motor neuron diseases of mankind.
The core intellectual property of AAVnerGene being licensed to KLTO is critical to the success of KLTO’s product development programs. If the patent applications do not result in a patent being granted and issued, the monetary payments and terms of the yet-to-be-executed “Definitive License Agreement” may be amended by the two parties at some future date.
Part I and Part II of the agreement will ultimately result in Part III, the GMP production of KLTO’s gene therapy candidates designated KLTO-202 and potentially Part IV and Part V. KLTO-101 and a third candidate, KLTO-303, may also be developed once a successful outcome and a collaborative relationship has been shown with KLTO-202.
Part I. AAVone Production Platform License Terms and Scope
1. | License Scope |
(a). AAVnerGene Inc. hereby grants Klotho Neurosciences the exclusive and global right to use the AAVone platform for development, manufacturing, and commercialization of gene therapy products based on the human Klotho gene isoforms for three clinical programs targeting:
■ | CNS-targeted secreted Klotho (Alzheimer’s and ALS - KLTO-101); |
■ | Neuromuscular-targeted secreted Klotho (ALS - KLTO-202) |
■ | Full-length human soluble- Klotho (KLTO-303) |
This exclusivity applies solely to these three pipelines based on human Kloto gene and does not extend to other therapeutic areas and genes unless otherwise agreed in writing.
(b). The current gene constructs (promoter and s-KL gene sequences) will be provided by KLTO investigators and used to create the AAVone construct. A second-generation “optimization program” for KLTO-202 may be funded and operationalized at some point in the future.
(c). Scope – KLTO-202:
● | Subclone GOI and (Heidelberg) capsid to AAVone |
● | Procedure optimization for small scales |
● | One batch 5 L-scale production and QC release |
● | Stability program for 4 time points. |
Deliverables:
● | pAAVone plasmids carrying GOI and (Heidelberg) Capsid |
● | One batch 5 L Drug Product |
● | Batch record |
● | Certificate of Analysis (CoA) |
● | Stability report |
(d). Scope – KLTO-101
● | Subclone GOI and (CNS targeted) capsid to AAVone |
● | Procedure optimization for small scales |
● | One batch 5 L-scale production and QC release |
● | Stability program for 4 time points. |
Deliverables:
● | pAAVone plasmids carrying GOI and (CNS targeted) Capsid |
● | One batch 5 L Drug Product |
● | Batch record |
● | Certificate of Analysis (CoA) |
● | Stability report |
(e). Part I Fees – two constructs – KLTO-101 and KLTO-202
Fee:$50,000 per candidate/pipeline; $100,000 for 2 candidates and $150,000 for three candidates.
Duration: 3 months
Part II. Preclinical License Stage & Tech Transfer to CDMO
License | Payment due | KLTO-202 | KLTO-101 | KLTO-303 | ||||||||||
AAVone License | Upfront | $ | 150,000 | $ | 200,000 | $ | 300,000 | |||||||
AAVone license | Maintenance | Free | Free | Free | ||||||||||
Tech transfer | Upon Delivery | $ | 100,000 | $ | 100,000 | $ | 200,000 | |||||||
Total | $ | 250,000 | $ | 300,000 | $ | 500,000 |
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Part III. Tech Transfer and CDMO Manufacturing – (Outsourced- N/A)
Stage | Price (USD) | |||
Project Management and Technology Transfer | 100,000 | |||
Establishment and Manufacture of Transfer Plasmid | $ | 250,000 | ||
Process Development (2L, 10L, 50L) | $ | 700,000 | ||
Analytical Development & Qualification | $ | 200,000 | ||
GMP HEK293 Cell Banking & Characterization | $ | 250,000 | ||
High-quality Grade Engineering Run (50L) | $ | 500,000 | ||
GMP Manufacture (50L) | $ | 700,000 | ||
Stability | $ | 200,000 | ||
Total | $ | 2,900,000 |
Part IV. Clinical License (Milestone-Based)
AAVone clinical License /indication | Payment due | KLTO-202 (USD) | KLTO-101 (USD) | KLTO-303 (USD) | ||||||||||
Upon IND filling and Phase I/II trials | Once IND NTC# is being awarded | $ | 150,000 | $ | 200,000 | $ | 300,000 | |||||||
Phase III | Upon completion of six (6) months of dosing in a Phase III clinical trial | $ | 150,000 | $ | 200,000 | $ | 300,000 | |||||||
BLA | 1 month post approval | $ | 1,000,000 | $ | 1,500,000 | $ | 2,000,000 | |||||||
Total | $ | 1,300,000 | $ | 1,900,000 | $ | 2,600,000 |
Part V. Commercial License Terms (Global and Exclusive License)
Royalty: 2% of Net Sales of licensed AAVone-based commercial products
<Signature Page Follows>
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Signature Page
AVVnerGene, Inc. and Klotho Neurosciences, Inc. agree to the general terms of this term sheet Agreement. A final definitive License Agreement shall be drafted incorporating the terms of this Agreement.
As agreed to on this date: July 16, 2025 | ||||
Klotho Neurosciences, Inc. | AVVnerGene, Inc. | |||
Signature: | Signature: | |||
/s/ Joseph Sinkule | /s/ Daozhan Yu | |||
Name: | Dr. Joseph Sinkule | Name: | Daozhan Yu | |
Title: | CEO and Chairman | Title: | CEO and Founder |
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