Autophagy Activator Drug Discovery Platform

VITA-FAST

Aging

Ageing is associated with the decline in the capacity of the autophagy pathway to degrade dysfunctional and damaging cellular components, such as protein aggregates and mitochondria. Dysfunctional autophagy, in turn, undermines other cellular functions including DNA repair, metabolism and survival. Therefore, activation of autophagy is considered a promising therapeutic approach to combat ageing and age-related diseases. A large number of screens has been performed and published to date, these have identified a wide range of small molecules that stimulate initiation of autophagy. Prof. Korolchuck lab proposes to initiate a drug discovery program with the aim of identifying novel bioactive autophagy inducers.

Owned by

0xf7990…96555

Contract:

0x6034e…33d36

Description

Team

Owner

Owner

Owner

Owner

Owner

Owner

Experiment Cost

$285,000.00

Project Score

Updated Aug 12, 2026

Technology Readiness Level

PRE-TRL

TRL 1

TRL 2

Price of VITA-FAST

$0.607

Project Progress

All updates

All categories

Timeline

Activity

Time	Type	$VITA-FAST	USD	ETH	From

Autophagy Activator Drug Discovery Platform

VITA-FAST

Aging

Owned by

0xf7990…96555

Contract:

0x6034e…33d36

Description

Team

Owner

Owner

Owner

Owner

Owner

Owner

Experiment Cost

$285,000.00

Project Score

Updated Aug 12, 2026

Technology Readiness Level

PRE-TRL

TRL 1

TRL 2

Price of VITA-FAST

$0.607

Project Progress

All updates

All categories

Timeline

Activity

Time	Type	$VITA-FAST	USD	ETH	From

Rationale

The VitaFAST project has conducted extensive in vitro experimental work, including high-throughput phenotypic screening of thousands of compounds, three rounds of NCE synthesis and testing, dose-response characterization, and target identification using multiple cell-based assay systems (Npc1-/- MEFs, autophagy flux assays, LC3 traffic-light imaging). However, no experiments have been completed in disease-relevant in vivo models — C. elegans studies were ongoing but proposed for cancellation, and murine disease model studies (Npc1-mutant mice) are planned but not yet performed. The experimental systems used are immortalized mouse embryonic fibroblast cell lines in 2D culture, which constitute simplified in vitro systems rather than advanced disease-modeling systems (patient-derived organoids, 3D tissue models) or in vivo disease models required for TRL 3 classification.

Assessment

Low Confidence

RecommendationSUPPLEMENT

Total Score3.50

Overall Assessment

VITA-FAST scores a 3.5 out of 5.0 on the weighted evaluation, reflecting a solid TRL 2 project with notable strengths and identifiable gaps. The project's strongest dimension is therapeutic relevance (4/5, weighted 1.8), driven by robust experimental validation of the autophagy-inducing mechanism across multiple cell models, identification of two novel targets, and strong scientific leadership from the Korolchuk Lab. The biological rationale is well-supported by peer-reviewed publications and conserved mechanisms from yeast to humans. Therapeutic optionality (4/5) is also strong given the breadth of potential indications (NPC, longevity, neurodegeneration, LSDs) and the dual NCE/repurposing development strategy, though these remain largely conceptual at this stage. The project shows moderate performance (3/5) across IP, candidate utility, and safety. While a patent has been filed for repurposed compounds and the FTO position appears favorable, the critical composition-of-matter patents for novel NCE leads remain unfiled — a notable gap given that lead compounds with 10-100x potency improvement have been identified. Drug candidates are emerging with promising cellular potency but lack formal pharmacological characterization (EC50/IC50) and any in vivo validation. Safety prospects are cautiously positive based on cellular data and the repurposed compounds' prior Phase 1 history, but no animal toxicology has been conducted. Overall, VITA-FAST demonstrates strong scientific foundations and a compelling mechanism of action appropriate for TRL 2, with clear next steps needed in IP protection of novel compounds, quantitative pharmacology, and progression to in vivo studies to advance toward TRL 3-4.

Weighted Score

Therapeutic Relevance

Early experimental results strongly support the hypothesis. Two novel autophagy-inducing targets (Autophagy1 confirmed, Autophagy2 hypothesized) have been identified, and the biological relevance is well-reinforced. VITA-FAST compounds induce autophagy at 10x the level of rapamycin. Three rounds of NCEs have been tested with three lead compounds showing 10-100x higher potency than earlier series. The mechanism of action — rescuing lysosomal dysfunction via autophagy activation — is validated across multiple cell models (Npc1-/-, Atg5-/-, Atg7-/-, FIP200/Rb1cc1-/-) with specificity controls demonstrating true autophagy-dependent rescue. Strong literature foundation from the Korolchuk Lab (H-index 56, 160+ publications) validates the autophagy-NAD axis across yeast, mouse, and human models. The only reason this is not a 5 is that formal EC50/IC50 values have not yet been reported and the second target (Autophagy2) remains at the hypothesis stage with the specific protein family member unconfirmed.

Therapeutic Optionality

Emerging findings clearly suggest multiple alternative applications beyond the primary NPC indication. The platform has broad applicability to longevity/aging, neurodegeneration (Alzheimer's, Parkinson's, Huntington's), other lysosomal storage disorders (Gaucher, Fabry, mucopolysaccharidoses), and metabolic diseases. Two lead repurposing molecules with prior Phase 1 data open a parallel clinical pathway. The identification of two novel targets that are 'previously proposed longevity targets' expands the therapeutic landscape. Combination approaches with NAD+ precursors and sirtuin activators have been identified. The dual development path (NCEs + drug repurposing via UAE) represents meaningful optionality. Scored 4 rather than 5 because these alternative pathways remain conceptual/early-stage and have not yet been experimentally validated beyond the primary autophagy assay system.

Intellectual Property

Early results are beginning to strengthen IP filings. A patent was filed on December 2, 2025 for repurposed compounds ('METHODS FOR ENHANCING AUTOPHAGY USING REPURPOSED PHARMACEUTICAL COMPOUNDS'), and VitaFast LLC (Delaware) has been formed to hold and manage project IP. The IP-NFT structure is registered on the Molecule protocol. Screened compounds show high chemical variability and no similarity to pre-existing autophagy inducers, suggesting strong novel IP potential. FTO analysis indicates a favorable position with differentiation from mTOR inhibitors and existing NPC therapies. However, composition-of-matter patents for the novel NCE lead compounds have not yet been filed (planned for H2 2025/Q4 2025), which is a significant gap given that three lead compounds with 10-100x potency have been identified. The IP strategy is still under development, and the filed patent covers only repurposed compounds (methods of use), not the novel chemical entities which represent the core value.

Utility Of Candidates

Potential drug candidates are clearly emerging. Three lead compounds have been identified with 10-100x higher potency than previous series, and two lead repurposing molecules with prior Phase 1 clinical data show high potency in autophagy assays. However, viability for achieving therapeutic effects remains partially demonstrated: formal EC50/IC50 values have not been reported, no in vivo efficacy data exists yet, and the computational optimization phase to further improve VF-series compounds is still underway. Round 2 NCE structural modifications did not improve target binding over Round 1, indicating SAR challenges that necessitated the pivot to computational optimization. The candidates are at an early stage — promising in cellular assays but unvalidated in animal models. The dual pathway (novel NCEs + repurposed compounds) provides some de-risking. Scored 3 because candidates exist and show promising potency but lack quantitative pharmacological characterization and in vivo validation.

Prospects For Safety

Early safety signals are cautiously positive. Lead compounds show no acute cytotoxicity at therapeutic concentrations in cellular assays, and the mechanism specificity is demonstrated (rescue in Npc1-/- but not Atg5-/- cells, confirming on-target activity rather than non-specific survival effects). The two repurposed lead molecules have prior Phase 1 clinical safety data, which significantly de-risks one development pathway. Worm healthspan and longevity studies are ongoing to assess systemic effects. However, no formal in vivo toxicology data exists for the novel NCEs, no ADMET/DMPK profiling has been completed, and IND-enabling murine safety studies are not planned until 2026. The mechanism of action (autophagy activation) is generally considered manageable but context-dependent (e.g., cancer implications). Scored 3 because early cellular safety data is reassuring and the repurposed compound pathway provides some safety validation, but comprehensive safety assessment is still ahead.