Reaction Biology‘s Drug Discovery Blog

Reaction Signals Q4 2025 Newsletter

Posted on by Evelyn Ma

ADCs Edition

Headlines In This Issue

Scientific Spotlight

ADC featured research: Kadcyla vs. Enhertu comparative study with SPR data and insights on what’s driving ADC innovation in 2025

Important Dates

See compound submission deadlines for multiple screening panels plus upcoming conferences

New at Reaction Biology

Capabilities and target expansion: 1000+ tumor cell lines now available

Scientific Highlight:

Antibody-Drug-Conjugates

Antibody-drug conjugates (ADCs) represent a significant advancement in targeted therapy, combining the specificity of monoclonal antibodies with the potency of cytotoxic agents. The success of ADCs depends on a complex interplay between the antibody, linker, and payload. Optimizing each component is critical to developing safe and effective therapeutics that maximize efficacy while minimizing off-target toxicity.

WEBINAR

Comparison of ADCs using Surface Plasmon Resonance (SPR)

Comparison of ADCs using Surface Plasmon Resonance (SPR)

Access our pre-recorded webinar by Allison Krajewski, Senior Scientist II, based in Malvern, PA, who walks through the comparative analysis of Kadcyla® and Enhertu® using SPR data.

Summary: The discussion focuses on HER2 binding kinetics and the impact of antibody engineering on ADC performance. Our SPR studies illuminated that similar HER2 binding doesn’t predict identical therapeutic behavior, as demonstrated by the contrasting cellular responses to Kadcyla and Enhertu despite their nearly identical receptor binding profiles.

POSTER

In Vitro Comparison of Kadcyla® and Enhertu® in Breast Cancer

In Vitro Comparison of Kadcyla® and Enhertu® in Breast Cancer

A complete comparative analysis

The SPR binding analysis featured in our webinar above was part of a comprehensive study designed to help clients understand the full mechanistic profile of leading ADCs in the HER2 space. This poster expands beyond the binding kinetics discussed in the webinar to present a complete comparative analysis of Kadcyla® (trastuzumab emtansine) and Enhertu® (trastuzumab deruxtecan) across multiple functional assays.

Our approach included SPR binding analysis (detailed in the webinar), real-time cell proliferation monitoring, internalization studies, bystander effect assays, and in vivo validation using the Hollow Fiber Model.

The results reveal a critical insight for ADC development: while both therapeutics demonstrate nearly identical HER2 binding kinetics, their downstream cellular behaviors diverge significantly, underscoring why comprehensive mechanistic profiling is essential for predicting clinical performance.

Key Findings:

  • Binding Paradox: Despite comparable HER2 binding affinities, Kadcyla® and Enhertu® exhibit distinct pharmacological behaviors across breast cancer cell lines with varying HER2 expression levels
  • Speed Advantage: Kadcyla® eliminates target cells more rapidly in direct cytotoxicity assays
  • Bystander Effects: Enhertu® demonstrates superior bystander killing effects that extend therapeutic impact to neighboring HER2-negative cells
  • In Vivo Efficacy and Safety Profiles: Although both ADCs exhibited distinct off-target toxicity profiles, including bone marrow suppression, only Enhertu demonstrated effective reduction of HER2-expressing SK-BR-3 cells – underscoring the vital need for a balanced evaluation of efficacy and safety in ADC development.

BROCHURE

Complete ADC Discovery Program Guide

Complete ADC Discovery Program Guide

From payload selection to GxP potency testing, explore our integrated ADC research solutions. The comprehensive guide details the broad portfolio of assays available to de-risk your program.

Whether you’re evaluating payload potency, optimizing internalization kinetics, or preparing for animal studies, this resource provides the information on ways Reaction Biology can help accelerate your ADC candidates toward clinical success.

INDUSTRY INSIGHTS


What’s Driving ADC Innovation in 2025?

The ADC field is rapidly expanding beyond oncology into immunology and other therapeutic areas. This expansion creates new opportunities to treat complex diseases with the same level of specificity and potency that ADCs have demonstrated in cancer treatment. Traditional ADC designs, comprised of a highly specific antibody, a stable but cleavable linker, and a powerful cytotoxic payload, have shown strong therapeutic potential. However, they still face limitations like imprecise payload release, less-than-ideal targeting, and limited overall efficacy.

We’re highlighting two recent publications that review innovations in ADC design (such as bispecific, immune-stimulating, and nanobody ADCs) and expansion of ADCs into other therapeutic areas.

Read the full publications:

Journal of Hematology & Oncology, 2025

Cancer Discovery, 2024

What this means for your program: Standard binding and cytotoxicity assays may not be sufficient for next-generation ADCs. Success requires integrated evaluation of payload mechanism, bystander effects, DAR optimization, and linker stability, such as the comprehensive profiling demonstrated in our Kadcyla® vs. Enhertu® studyabove, where identical binding produced dramatically different therapeutic profiles. Moreover, our in-vivo hollow fiber model offers a promising system for simultaneous evaluation of both efficacy and toxicity within the same in vivo assay.

Upcoming Screening Schedule

Ensure your compounds are included in our upcoming screening runs. Please note the following deadlines for sample submission.

Request a quote for compound screening →

Bromodomain Full Panel

October 21 | November 26 | January 2, 30

Learn more about reader bromodomain assay services →

Protease Full Panel

November 7 | December 5 | January 23

Learn more about protease assay services →

Phosphodiesterase (PDE) Full Panel

October 17 | November 14 | December 12 | January 23

Learn more about PDE assay services →

ProLiFiler™ Cancer Cell Panel

October 24 | November 21

Learn more about ProLiFiler assay services →

Histone Deacetylase (HDAC) Full Panel

October 31 | November 26 | January 2, 30

Learn more about HDAC assay services →

InVEST44 Safety Panel

October 17 | November 14 | January 9

Learn more about in vitro safety panel services →

Methyltransferase Full Panel

October 24 | November 7, 21 | December 5 | January 2, 16, 30

Learn more about methyltransferase assay services →

Kinase Panel Screening (US Facility):

Full Panel: October 15, 29 | November 12, 26 | December 31 | January 14, 28

1 mM ATP (Wildtype, Mutant, Atypical, Lipid): October 22 | November 19 | December 10 | January 21

Diversify Panel: November 5 | December 3 | January 7

Kinase Panel Screening (German Facility)

Full Panel: October 30 | November 27

Learn more about kinase panel services →

Product Highlights: Newly Added Offerings

1,000+ Tumor Cell Lines Now Available for Proliferation Screening

1,000+ Tumor Cell Lines Now Available for Proliferation Screening

We now offer access to over 1,000 tumor cell lines for cell proliferation and viability screening. Our BSL-2 certified facilities enable work with patient-derived cells and custom cell line establishment.

  • Multiple validated formats: CellTiter-Glo, MTT, CyQUANT, BrdU, and more
  • IncuCyte real-time imaging and cell cycle analysis
  • Drug combination testing for synergy studies
  • High-throughput screening infrastructure

Learn more about cell proliferation and viability screening →

Conferences and Events

Drug Discovery 2025

  • Date & Location: October 21-22 | Liverpool, UK
  • Booth: A01

AACR-NCI-EORTC

  • Date & Location: October 22-26 | Boston, MA
  • Featured Poster: A smarter route to the brain: Preserving the BBB in preclinical brain tumor models – Presented by Dr. Cheryl Davis, US Head of In Vivo

16th Annual World ADC San Diego

  • Date & Location: November 3-6 | San Diego, CA
  • Booth: 74
  • Featured Poster: In vitro comparison of Kadcyla® and Enhertu® in breast cancer with varying HER2 expression – Presented by Dr. Helen Ketteringham, Associate Director, In Vitro

13th PharmaLab Congress

  • Date & Location: November 24-26 | Düsseldorf, Germany
  • Booth: 6 (Bioassay GmbH, a Reaction Biology company

14th Tumor Models Summit

  • Date & Location: December 2-4 | London, UK

 

About Reaction Biology

Experts in Supporting Innovation

Reaction Biology specializes in answering your complex scientific questions to accelerate the development of your breakthrough therapeutic candidates. For over 20 years, leading pharmaceutical, academic, and biotech organizations worldwide have relied on our labs as the partner of choice to advance their most promising drug candidates and research pipelines.

Our track record speaks for itself: we’ve served over 2,000 clients across more than 5,000 projects every year. We act as an extension of your team and operate with the speed, precision, and scientific rigor that you demand to meet your critical research milestones.

With strategically located facilities in the US and EU, we provide streamlined operations, quick turnaround times, and secure handling of your most sensitive research materials.

Our broad discovery and development services portfolio spans capabilities from protein production to in vivo, backed by an expansive library of over 2,000 validated drug targets and 1,000+ cell lines. Our global, multidisciplinary experts deliver custom and tailored solutions with a demonstrated track record of success, including innovative therapies approved by the FDA and other global regulatory agencies.