NMS ADC Platform

NMS ADC integrated platform of payload linkers

Antibody-Drug Conjugates (ADCs) are groundbreaking in the realm of targeted cancer therapy, marrying the specificity of monoclonal antibodies (mAbs) with the potent killing power of cytotoxic drugs. Their design leverages the precision of antibody targeting to deliver cytotoxic agents directly to cancer cells, thereby sparing normal, healthy cells from the toxic effects of chemotherapy. This approach enhances the efficacy of the drug and minimizes side effects, offering a promising treatment option for various types of cancer.

ADCs are a highly sophisticated pharmaceutical, made of three main components:

- - Monoclonal antibody (mAb) – targets specific tumor antigens.
  - Linker – connects the mAb to the cytotoxic drug.
  - Payload – cytotoxic drug delivered specifically to cancer cells.

Combining the specificity of antibodies with the lethal potency of cytotoxic drugs paves the way for more effective and less toxic cancer therapies.

The innovative design of ADCs represents a significant advancement in oncology, offering hope for more effective treatments with fewer side effects.

NMS is at the forefront of developing these cutting-edge therapies, contributing to the future of cancer treatment.

Nerviano Medical Sciences’s edge in ADC technology: integrating key research expertise to create next-generation ADCs

Developing fully functional ADCs is a sophisticated process that necessitates a multidisciplinary approach, integrating insights and techniques from molecular biology, chemistry, pharmacology, and bioengineering

NMS, with decades of expertise, innovates and integrates the various components and processes involved in ADC development to address emerging limitations in the field including chemoresistance and limited therapeutic window

NMS portfolio includes optimized duocarmycin (NMS-P945), anthracycline, and targeted payloads tailored to effectively treat diverse tumors with enhanced specificity. Utilizing a rigorous screening process, and a multifunctional approach to target selection, NMS delivers unparalleled ADC development opportunities with enhanced efficacy and safety

NMS’s unique fully integrated approach is a strategic advancement in the ADC field

Payload Identification

Starting from proprietary historical data and chemical collections, payloads are prioritized based on proliferation, safety and efficacy data, together with chemical feasibility and diversity

Payload Linker Identification

Payloads prepared with different linkers are prioritized based on chemical stability and payload release

Target identification

Starting from payload(s) features, a multidimensional approach including tumor sensitivity, medical need and competition drives the selection of the best suited target(s) for each payload-linker

ADC generation

Developing and prioritizing ADCs involves a rigorous evaluation of multiple critical parameters including Drug Antibody Ratio (DAR), aggregation, binding, antiproliferative activity in target (+) and target (-) cells, bystander effect, immunogenic cell death and plasma stability

ADC preclinical validation

The process involves extensive testing in both in vitro and in vivo models to assess key aspects of preclinical validation such as efficacy in CDX and PDX models, and pharmacokinetic properties

NMS’s portfolio of payload linkers: expanding the ADC landscape enhancing the effectiveness and precision of cancer treatment

NMS established a unique platform of cytotoxic and targeted payload linkers with peculiar features to develop the best ADC for any given target or tumor type:

NMS-P945 is a duocarmycin-based payload linker, acting as a DNA damaging agent and demonstrating strong bystander effect, high in vivo efficacy with cured mice and good safety profile suitable for chemo resistant highly heterogeneous solid tumors (Mol Cancer Ther (2023) 22 (12): 1465–1478)

Next generation anthracyclines are topoisomerase II inhibitors showing outstanding immunogenic cell death properties, superior efficacy and safety profile to PNU payload suitable to revert cold into hot tumors (AACR2024, NMCS_ACS2024 posters)

Novel targeted payloads with diversified mechanisms of action and to be developed with selected targeted antibodies to reach a unique selectivity and increased safety profile compared with current ADCs (WADC-EU 2024 poster)

Target-Payload matching via a multidimensional approach based on individual payload(s) features, tumor settings and market perspectives. Potential for increased selectivity and greater therapeutic window in patients

– – – – – – – – – –
See the poster presented at:

– AACR 2024 “A novel platform of diversified cytotoxins and targeted payloads to drive ADC innovation”

– ACS 2024 ”Development of 14-amino-anthracyclines as novel payloads for ADC production showing potent anti-tumor activity and improved safety profile”

– WADC Europe 2024“A payload-linker generating machine to quickly move from small molecules to characterized tool ADCs and PDCs”