What is drug repurposing and why is it used for shelved compounds?

Drug repurposing (or repositioning) is the process of finding new therapeutic uses for existing, approved, or failed drugs. It's often applied to shelved compounds because they already have significant safety and preclinical data, drastically reducing the time and cost compared to developing a completely new drug.

What is the GRIP platform and how does it aid drug repurposing?

The GRIP (Global Repurposing Integrated Platform) is Excelra's proprietary platform that combines over 40 public and proprietary databases to create multi-dimensional profiles of drugs, diseases, and targets. It uses proprietary algorithms to perform in silico analysis and generate testable biological rationales for new indications.

How many alternate indications were identified and what was the most notable outcome?

A total of 30 alternate indications were identified and validated across the six shelved compounds. The most notable outcome was the successful repositioning of a preclinical asset (originally for an autoimmune disorder) for Alzheimer’s disease, leading to an IND filing.

How did the multi-omics analysis validate the in silico predictions?

The multi-omics analysis used the client's drug-treated in vitro and in vivo genomics and metabolomics data. The results were then used to corroborate the initial in silico analysis from the GRIP platform, providing a strong biological rationale and wet lab validation for the final list of recommended indications.

What types of compounds does Excelra's drug repurposing service handle?

Excelra's drug repurposing services handle a wide range of assets, including preclinical compounds and clinical assets that failed in Phase II and Phase III development, providing strategies to maximize value across the entire R&D pipeline.

Does this integrated strategy only rely on computational analysis? (Service-based)

No, the strategy is fully integrated. It combines in silico analysis (computational prediction using GRIP) with validation through wet lab data (multi-omics analysis). This two-step corroboration ensures the robustness and testability of the final recommendations.

Case studies

30 alternate indications identified for six shelved compounds

A large pharma company was looking to expand its portfolio for six shelved assets (four failed in clinical development Phase II & III and two at the preclinical stage) using drug repurposing.

Overview

This case study demonstrates the power of drug repurposing in expanding a pharmaceutical company’s portfolio. A large US pharma was looking to revitalize six shelved compounds (four failed in clinical Phase II/III, two at preclinical stage). We applied an integrated strategy combining proprietary in silico analysis using our GRIP platform with wet lab validation via a multi-omics approach. This combined workflow ultimately led to the identification and corroboration of 30 alternate indications for these assets, successfully advancing one compound to an IND filing and demonstrating significant value realization from previously failed assets.

Our client

The client is a large pharma company based in the US, operating in the pharmaceutical industry across multiple sectors.

Client’s challenge

The client faced the challenge of maximizing value from shelved compounds—assets that failed in late-stage clinical trials or were discontinued early in preclinical development. The goal was to identify and validate alternate indications for these assets using a scientifically robust, integrated strategy that combined computational predictions with experimental confirmation.

Client’s goals

The client’s core objective was to utilize an integrated strategy for drug repurposing.

Identify alternate indications

Systematically generate a list of new potential therapeutic areas for the six shelved compounds.

Validate hypotheses

Corroborate the predicted indications through two independent workflows: in silico analysis and wet lab experiments (multi-omics analysis).

Expand portfolio

Leverage data-driven approaches to expand their pipeline by giving a second life to these failed or discontinued assets.

Our approach: integrated drug repurposing strategy

We analyzed the six compounds using a comprehensive, multi-step pipeline that combined our proprietary digital platforms with wet lab validation.

In silico analysis using the GRIP platform

Our novel and proprietary drug repurposing platform, GRIP (Global Repurposing Integrated Platform), allows for an integrated approach by leveraging core components to generate biological rationale for new indications.

Global repurposing integrated database (GRID)

This customized database is a compendium of $40+$ public and proprietary databases, including GOSTAR and GOBIOM. It creates multi-dimensional profiles of biologically relevant entities like genes, pathways, biomarkers, and adverse events. (Learn more about GOBIOM’s biomarker database for enabling precision medicine).

The holy trinity

We established 3-way relationships between drug, disease, and target to help understand relevant associations. (This ties into our Target intelligence for data-driven drug discovery).

Algorithms

Customized proprietary algorithms mined the drug-target-disease associations from GRID.

Analytics & visualization

In-house analytical capabilities and visualization tools enabled the identification of hidden connections between drugs, disease, and targets.

In silico analysis workflow showing data inputs and components of the GRIP platform for drug-disease-target associations.

Multi-omics validation

Following the in silico analysis recommendations, the client shared drug-treated in vitro and in vivo genomics and metabolomics data for the assets.

The multi-omics analysis consisted of analyzing this data to further validate the shortlisted alternate indications recommended by GRIP.
The results from the multi-omics analysis were used to corroborate the in silico analysis, leading to the final recommendations supported by robust biological rationale. (This complements our expertise in Illuminating the path to faster discoveries with Bioinformatics).

Multi-omics validation workflow: steps including experimental design, in vitro/in vivo experiments, data generation, and data analysis for shelved compounds.

30-alternate-indications-identified-for-six-shelved-compounds

Conclusion

The combined approach of in silico analysis and multi-omics validation helped expand the client’s portfolio significantly, transforming liability into asset value through effective drug repurposing.

We identified 30 alternate indications for the six shelved compounds, which were validated in silico and in vitro/in vivo.
One of those compounds, a preclinical asset initially shelved for a gastrointestinal/autoimmune disorder, was repositioned for Alzheimer’s disease and successfully progressed to IND filing. (This aligns with our focus on Accelerated drug repurposing using advanced analytics).
We successfully repurposed a compound for a new indication using lipidomics data, even though its target/mechanism of action was previously unknown. (This showcases the value of Data science to unlock the power of data).
For a compound discontinued due to hepatotoxicity, we identified an alternate use requiring topical administration. (Our services span multiple areas, including Scientific informatics and application development).
This case study underscores the immense value of leveraging data-driven approaches for drug repurposing to rescue shelved compounds and streamline portfolio management.

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