Case Study

Prioritizing Combinatorial Therapy Sensitivity for Drug Development in Primary Liver Cancer

Background

In Primary Liver Cancer (HCC), most targeted therapies show poor efficacy in clinical trials, including proteasome inhibitors.

Method

Optim.AI™ was applied on patient-derived HCC avatar models to investigate combinatorial strategies that could improve tumor sensitivity to these drugs.

Results/Findings

Optim.AI™ analysis revealed that pairing CDK inhibitor Dinaciclib with 2nd generation proteasome inhibitor Ixazomib could enhance the therapeutic potential of each drug / showed greater anti-tumor efficacy.

Conclusion

When applied in the right combination, a previously ineffective or underutilized drug can still be used effectively for treatment.

Rashid et al., Sci Trans Med (2020)

(A)PDX tumors and their corresponding PDX-derived organoids (PDXO).
(B)Optim.AI™ analysis shows the combination of Ixazomib and Dinaciclib (Ixa+Dina) as the drug pair with lowest mean viability across different PDXOs.
(C)Pairing Ixa and Dina enhances tumor sensitivity to treatment, compared to monotherapy.

Others Case study

Combination Design

Partner with IND-ready asset showing limited monotherapy efficacy despite genetic target validation in 20% of solid tumors

Evaluated partner asset+15 drugs of interest across 6 solid tumor lines (3 different indications) at 3 dose levels in 2 months

Identified efficacious combinations across all cell lines that outperformed standard of care

Specifically for gastric cancer, validated results highlighted that a commonly used chemotherapy, normally given at very toxic levels, exhibited high efficacy at much safer doses when in combination with partner’s asset

Target Prioritization

Partner with nucleic acid therapeutics (NAT) group interested in targeting oncogene-specific synthetic lethality

Evaluated 8 potential targets within the context of MYC-driven liver cancer in at a fraction of time and cost of high throughput screening

Mapped all possible drug-drug and target-target interactions

Identified the best synthetic lethality target that synergized with a specific DNA damage response inhibitor

KYAN Therapeutics Announces Collaboration with Institute of Molecular and Cell Biology for Accelerated Drug Discovery and Development of Nucleic Acids

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