ADC CHARACTERIZATION AND EVALUATION
Coupling heterogenicity and accuracy
By combining the specificity of an antibody with a cytotoxic payload, antibody-drug conjugates (ADCs) have unlocked new oncology treatments with a high therapeutic index, reduced off target side effects and improved tumor clearance. Many new ADC therapies remain to be discovered As new tumor antigens are discovered, new ADC therapies become possible, while new linkers allow delivery of more drug conjugates.
The complexity of ADCs is driven by three separate properties that need to be optimized: antibody specificity, conjugate payload, and linker strategy. Achieving the desired pharmacokinetics can be challenging. You may need to reconcile the desired drug antibody ratio (DAR) and the number of potential conjugation sites. Conjugation methods that are not site-specific result in heterogeneous ADCs that vary in both DAR and conjugation sites, which may lead to off-target, off-tumor effects. Antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) are additional properties you may want to engineer into, or remove from, your ADC. Achieving the right balance of ADCC, CDC, & ADCP requires careful engineering of the antibody and confirmation by in vitro testing. You may also want to optimize for minimal aggregation. Pharmalegacy has the capabilities to design and execute robust assay systems enabling you to optimize all of the many properties of your ADCs and deliver the next breakthrough therapy.
Not working in oncology? We can optimize ADCs in many fields. Second and third generation ADCs are delivering diverse payloads for anti-inflammatories, kinase inhibitors and many other agents. Pharmalegacy has decades of experience working with a wide range of compounds across a multitude of indications.
When creating the next breakthrough ADC you need a robust and experienced partner who can get you accurate answers to your in vitro and in vivo pharmacological questions. With more than 400 FDA / CFDA IND filings and a scientific staff with an average of over 15 years of pharmacology experience, PharmaLegacy can be this partner. Let us efficiently guide your ADC pipeline into human trials.
MODELS / SERVICES
- Highly equipped animal facility with > 70,000 ft2 total space
- Full facility for small and large animals
- Maximum capacity: 30,000 rodents, 320 NHPs, 300 dogs and 350 rabbits
Strong Bioanalytical Capabilies
PharmaLegacy supports antibody-drug conjugate pipelines from discovery through IND.
Common Bioanalytical Methods:
- Total ADC (conjugated)
- ELISA
- Total Antibody
- ELISA
- Free Payload
- LC-MS/MS
Special Bioanalytical Methods (when ELISA cannot be used):
- Total ADC (conjugated)
- LC-MS/MS
- Total Antibody
- LC-MS/MS
- Free Payload
- LC-MS/MS
DMPK - ADC Bioanalysis with ELISA
DMPK - ADC Bioanalysis with LC-MS/MS
Total Antibody Quantitation:
- Sample clean-up
- Reduction
- Alkylation
- Digestion
- Analysis with LC-MS/MS
Total ADC Quantitation:
- Immunocapture
- Enzyme digestion
- Special treatment
- Analysis with LC-MS/MS
Cell line-Derived Xenograft
- Over 20 cancer types
- Over 200 validated tumor models (new models added continuously)
- Provide tumor growth curve with SOC validations
- Subcutaneous, orthotopic, systemic, experimental metastatic
- Certain drug-resistant in vivo models available
Syngeneic Models
- 40+ in vivo models
- Subcutaneous, orthotopic, resection settings
- Fully characterized in immunotherapy and combination therapies
- Full ex vivo analysis platform: flow cytometry, IHC, ELISA, ELISpot etc.
Humanized Models
- Multiple human antigen KI models
- 20+ HuPBMC models with validated donor screening
- Routine HuCD34+ HSC humanized model generation, no-waiting cohort
- 40+ established HuCD34+ HSC humanized models (new models added continuously)
- 2nd generation HuCD34+ with enhanced human myeloid cell expression
Case Study
JIMT-1 xenograft in CB17/SCID mice
Committed to quality:
- Completed over 400 FDA / CFDA IND filings
- AAALAC accredited vivarium
- 24/7 access to PharmaLegacy representatives
- 380,000 square feet of facility space
Looking for a CRO that can deliver pipeline breakthroughs? Contact PharmaLegacy.
Providing Better Data for Critical Immuno-Oncology Pipeline Decisions
PharmaLegacy works to get you the answers you need with our wide selection of carefully developed in vivo and in vitro models. In this document, you’ll see a sample of the in vitro assays we run along with a sample of real-world data from them. See why over 700 pharmaceutical companies, including many global leaders, trust PharmaLegacy for the unbiased, accurate information they need to make critical pipeline decisions.
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