Antibody-Drug Conjugates (ADCs)

ADCs deliver highly potent chemotherapy agents directly to cancer cells via a linker attached to a targeted antibody. Unlock the full potential of antibody-drug conjugates with our comprehensive services & solutions.

Home – Biologics – Bioconjugates & ADCs – Antibody-Drug Conjugates (ADCs)

The leading ADC CDMO partner from design to development and manufacture.

Antibody-drug conjugates (ADCs) are demonstrating to be incredibly effective but historically difficult to get through trials. To avoid costly failures in downstream manufacturing or in the clinic, we use our expertise and state-of-the-art technologies to do things properly at the outset of your program, so that you start smart, and finish fast.

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We are committed to moving this next generation of medicine forwards. Abzena’s 20+ years of bioconjugation experience and ThioBridge™ ADC design and delivery solution simplifies and accelerates the development process. Our ADC development services provide:

  • Early de-risking & optimization
  • Process development & optimization
  • Formulation development
  • Analytical method development
  • Linker payload design & synthesis
  • Clinical to commercial manufacture

What are Antibody-Drug Conjugates (ADCs)?

ADCs are an iteration of a well-established concept: using antibodies to deliver toxic payloads directly to cells, serving as a molecular rifle-scope, targeting and killing tumor cells… but how do they work?

Cancer treatment with ADCs

Developers have long since understood the power of specifically targeting harmful cells and delivering a cytotoxic payload with minimal systemic toxicity – particularly in the treatment of cancer. As a result, ADCs are one of the fastest growing anti-cancer therapeutic areas.

2000

Year of the first ADC approval

12

ADC drugs approved for marketing worldwide*

$22.87 Billion

Predicted ADC market size in 2030

*As of early 2024.

 

 

How do ADCs work?

ADCs are comprised of three main components:

  1. An antibody – typically a monoclonal antibody (mAb)
  2. A linker
  3. A cytotoxic payload

The mechanism of action of ADCs is complex, often requiring internalization, intracellular processing and payload release.

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ANTIBODY

The antibody subunit provides specificity towards cancer cells by recognizing antigens exclusive to, or highly expressed by, cancer cells. Upon recognition, the ADC enters the cell, and the linker is degraded, releasing the cytotoxic.

CYTOTOXIC DRUG

Most cytotoxic drug components are highly potent and belong to two major families: tubulin and DNA-damaging agents. Inappropriate release of these drugs can cause toxic effects, so the drug must remain attached to the antibody until internalization.

LINKER

The antibody and cytotoxic drug component are generally linked by a covalent linker. Peptide linkers are the most common type, offering stability and the ability to be selectively cleaved by lysosomal proteases following cell uptake.

ADCs in action: Understanding the molecular “rifle-scope” mechanism

  1. ADC administered to patient via intravenous injection
  2. Antibody component specifically recognizes and binds to cancer cell receptor
  3. Internalization via receptor-mediated endocytosis
  4. ADC in endosome
  5. Lysosomal proteases degrade ADC, releasing cytotoxic drug
  6. Cytotoxic payload free to interact with internal targets
  7. Cell undergoes apoptosis (programmed cell death)
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Advancements adding complexity

Development and manufacturing of ADCs is becoming increasingly challenging. For each product, unique hurdles to ADCs must be carefully considered and overcome, and must ensure:

  • Antibody specificity only to target cells to avoid healthy cell destruction
  • Maintained antibody affinity to target epitopes following conjugation
  • Avoidance of immune activation and/or neutralization by native patient antibodies
  • Improper release of the cytotoxic payload
  • Highly potent anti-tumor activity regardless of only a fraction of the dose being delivered.

The ADC revolution

Advances in molecular engineering techniques have translated into the components of ADCs becoming increasingly sophisticated, offering:

  • Cytotoxic payloads with diverse mechanism of action
  • Refined linkers
  • More complex antibodies

 

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Bioconjugate & ADC Services

Abzena are experts in developing Antibody Drug Conjugates (ADCs) through all stages from discovery to commercialization.

Bioconjugate & ADC Design

Experienced in the development of robust and reliable conjugation methodologies, our pre-clinical discovery teams work with you to optimize your Bioconjugates and Antibody Drug Conjugates.

Bioconjugate & ADC Design

Bioconjugate & ADC Development

We partner with you to apply the optimal set of bioassays and analytics that assess the developability of your antibody-drug conjugate. This ensures the lead candidate you take forward has reduced liabilities and a de-risked development path.

Bioconjugate & ADC Development

Linker Payloads

Leverage our experience in the synthesis of payloads, linkers, and payload-linker constructs.

Linker Payloads

Analytics & Bioassays

Our ADC analytics and bioassay services give you all of the rapid insight and data needed to help make informed decisions earlier.

Analytics & Bioassays

Formulation Development

Align your drug to your preferred target product profile (TPP) with our formulation development packages including stable liquid and lyophilized formulations.

Formulation Development

Process Development & Optimization

We can ensure seamless scale up through to commercial launch.

Process Development

ADC Manufacturing

We have developed an efficient, scalable, validated, cost-effective bioconjugate and ADC manufacturing process.

ADC Manufacturing

A Bioconjugation & ADC CDMO partner you can trust

To accelerate lead drug candidate selection, we utilize our expertise in identifying and mapping the appropriate design space for the development of your complex Antibody-Drug Conjugates (ADCs). Through the application of our developability assessments, we identify and de-risk your clinical candidates for development and ensure stage-specific milestones are met.

Bioconjugate & ADC Development

Designing the best ADC matrix strategy

To optimize the design of your molecule, our expert team applies their experience to design the best ADC matrix strategy for you. Your program will benefit from our extensive knowledge of ADCs and bioconjugation. We have experience in the design and development of fully characterized ADCs with a wide range of conventional and novel linkers, cytotoxins, and other payloads. In addition, we provide a range of both proprietary and non-proprietary PEGylation technologies.

Robust, critical early development processes

Our experts develop robust conjugation processes maximizing conversion to the target species and purification strategies allowing isolation with high recoveries and purity. Critical process parameters are identified at an early stage to ensure the development of a conjugation process, accelerate your lead candidate, and ensure scale-up of manufacturing.

ThioBridge™: ADC Development Platform

Our unique ThioBridge™ platform is truly next-generation conjugation technology. It overcomes some of the shortcomings of first-generation conjugation technologies, by using site-specific conjugation to antibody interchain disulfide. It offers a more uniform DAR profile and stable attachment compared to maleimide conjugation and allows for PK profiles to be optimized with architectural design flexibility when it comes to the payload and spacer.

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