Test the efficacy of your compound(s) in a panel of 25 patient-derived organoids representing colorectal, lung, and pancreatic cancer. Our advanced screening capabilities include:
- Direct measurement of cell viability with an image-based viability readout
- High-throughput 3D assay format
- Test any number of compounds, with no minimum number of models to enroll
- High-dose quality with 10-point dose-response curves per compound
- Inclusive of IC50 determination and heatmap generation
Accelerate your KRAS drug development with our comprehensive portfolio. Identify promising leads and understand compound mechanism of action to investigate and develop novel therapies. Book a consultation now!
Preset KRASmut panel features
- Largest commercially available KRASmut PDO panel, with 25 models that represent pivotal KRAS mutants including G12A, G12D, G12V, G13D and many others
- Rigorously characterized with readily available RNA or DNA sequencing data
- Diverse models encompassing both primary and metastatic tumors, with the ability to test off-tumor toxicities with matched normal organoids
- Models with WT KRAS that can be added to this 25 model panel
Applying our KRASmut PDO screen
Our meticulously designed KRASmut panel was instrumental in developing a clinical candidate using organoid technology targeting head & neck cancer. Discover our proof-of-concept study and learn how PDOs can be used to accelerate your preclinical therapeutic development.
Mutation-specific KRASmut panel features
This organoid panel includes allele-resolved patient-derived models for KRAS-targeted drug development. We provide mutation-specific panels drawn from a biobank of over 50 patient-derived organoids carrying clinically relevant KRAS driver mutations. Each panel is assembled by confirmed mutated allele and indication to support efficacy testing, combination optimization, and resistance characterization in models that preserve patient tumor biology. The panel has also been benchmarked for response against daraxonrasib, an approved multi-KRAS inhibitor.
The challenge involves the development of a next-generation inhibitor that can hold up as a monotherapy where the first generation could not and the identification of a more effective combination partner. This requires preclinical systems that retain the complex mutation background, tissue context, and adaptive signaling capacity of patients. Conventional 2D cell lines do not preserve these features, and allele- and indication-specific questions require sufficient model depth within a single mutation.
Platform specifications
- Model characterization: RNA and DNA sequencing data available, including co-mutation status
- Tumor origin: primary and metastatic models
- Controls: genetically matched normal organoids for off-tumor toxicity assessment
- Viability readout: direct image-based measurement
- Assay format: high-throughput 3D
- Dose-response: 10-point curves per compound per model
- Analysis: IC50 determination and IC50 heatmap generation
- Compound number: unrestricted
Studies may be configured using the preset KRASmut PDO Screen, a single mutation-specific panel, or a combination of both; consult with our scientific team for more information.
G12D – 23 PDOs
Colorectal 14, Pancreatic 8, Ovarian 1
Study types:
- Combination screening across all 20 PDOs — compound as monotherapy and in combination with EGFR or PI3Kα inhibition, at model number sufficient to resolve the interaction
- Colorectal responder stratification — 13 colorectal PDOs enable identification of the sensitive subset and its associated co-mutation background
- Cross-indication efficacy comparison — colorectal, pancreatic, and ovarian models profiled under identical assay conditions
- Pancreatic benchmarking against the reported activity profile of clinical-stage G12D inhibitors
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, and underlying image-based viability data, with per-model sequencing data available for interpretation.
Best for: Combination strategy development, stratification hypothesis generation, indication selection.
G12C – 7 PDOs, colorectal
Induced resistance model included with studies exceeding 4 PDOs
Study types:
- Anti-EGFR combination screening across all 7 colorectal PDOs — compound as monotherapy and in combination with cetuximab or panitumumab, resolving combination dependence at model level
- Comparative efficacy analysis against sotorasib and adagrasib, as monotherapy and in anti-EGFR combination
- Post-progression activity assessment in Induced Resistance Models generated by progressive exposure to approved G12C inhibitors
- Responder stratification against co-mutation background rather than aggregate response
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, and underlying image-based viability data.
Best for: Next-generation G12C inhibitor positioning, colorectal combination rationale, comparative differentiation packages.
G12V – 12 PDOs
Colorectal 7, Pancreatic 2, Ovarian 1, Lung 1, Fallopian 1
G12V accounts for approximately 30% of KRAS-mutant pancreatic cancer and is the second most prevalent KRAS allele, with no selective inhibitor currently approved. Development activity is concentrated in pan-RAS, PROTAC, active-state, and immunotherapeutic approaches. G12V has additionally been reported as an acquired resistance allele in patients progressing on G12C inhibitors, extending the relevance of these models to G12C programs.
Study types:
- Four-indication efficacy profiling — colorectal, pancreatic, ovarian, and lung G12V PDOs under identical assay conditions
- Resistance-coverage assessment — evaluation of compound activity against G12V as an emergent resistance allele in G12C-treated disease
- Ovarian cancer data generation — an indication with limited representation in commercially available KRAS panels
- Combination screening with EGFR, MEK, or alternative partners where monotherapy activity is modest
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, underlying image-based viability data, and cross-indication comparison across all four tumor types.
Best for: G12V-selective, pan-RAS, PROTAC, and active-state inhibitor programs; first-in-class indication strategy.
Rare G12 variants — 5 PDOs
Colorectal 3, Pancreatic 1, Head & neck 1
Rare G12 alleles including G12A, G12S, and G12R are individually infrequent but collectively substantial, and constitute the test of pan-KRAS and pan-RAS coverage claims. G12R exhibits distinct biochemical behavior relative to other G12 variants. These alleles are commonly excluded from commercially available panels.
Study types:
- Allele-coverage profiling across G12A, G12S, G12R, and additional variants, generating the breadth data required to substantiate pan-KRAS claims
- G12R-specific characterization, establishing whether compound mechanism generalizes across biochemically divergent G12 variants
- Head & neck cancer data — the sole head & neck model in the KRAS collection, and the indication underlying the first clinical candidate developed using organoid technology
- Coverage gap identification in advance of partnering or regulatory review
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, underlying image-based viability data, and an allele-resolved coverage profile.
Best for: Pan-KRAS and pan-RAS breadth substantiation, partnering and regulatory documentation, rare-allele inclusion criteria.
G13 — 5 PDOs
G13D 2, G13C 1, Colorectal
G13D occurs predominantly in colorectal cancer and has a long-examined relationship to anti-EGFR benefit. Codon 13 mutants occupy a distinct biochemical regime from codon 12, with altered intrinsic nucleotide exchange and GAP sensitivity. G13C, as a cysteine mutant at an alternative position, is of specific interest for covalent chemistry developed against G12C. Patient-derived organoids carrying G13 alterations are scarce commercially.
Study types:
- Covalent selectivity assessment — determination of whether a G12C-directed warhead engages cysteine at codon 13
- Codon 12 versus codon 13 comparison — identical compound profiling across G13 and G12 PDOs to establish positional dependence
- Anti-EGFR combination screening with cetuximab or panitumumab in the indication in which the G13D question originated
- Activity profiling in alleles without approved or clinical-stage selective inhibitors
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, underlying image-based viability data, and direct comparison against codon 12 models on request.
Best for: Covalent selectivity characterization, undrugged allele exploration, colorectal anti-EGFR combination rationale.
Q61 variants — 5 PDOs
Colorectal 3, Pancreatic 1, Fallopian 1
Q61 mutations reside in the catalytic machinery rather than the switch-II pocket targeted by the majority of approved and clinical-stage KRAS inhibitors, impairing GTP hydrolysis through a distinct mechanism. Activity in Q61 models therefore constitutes direct evidence of pocket independence. Codon 61 alterations have additionally been reported among acquired resistance events in patients treated with G12C inhibitors.
Study types:
- Pocket-independence assessment — compound activity in an allele class outside the switch-II binding site
- Pan-RAS coverage validation beyond codon 12, across three tumor indications
- Mechanism-of-action characterization for active-state and allosteric agents against an alternative hydrolysis-impairment mechanism
- Forward-looking resistance profiling relevant to G12C programs anticipating codon 61 emergence
Data delivered: 10-point dose-response curves per compound per model, IC50 determination, IC50 heatmaps, underlying image-based viability data, and three-indication comparison separating allele from tissue effects.
Pan-RAS and active-state inhibitor validation, mechanism characterization, breadth assessment beyond the switch-II pocket.
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