Our Science
Our Science

Our Science

Curie is broadly developing targeted radiopharmaceuticals for the treatment of high unmet need solid tumors, by pursuing a multimodal drug discovery and development approach.
What are radiopharmaceuticals?

What are radiopharmaceuticals?

A radiopharmaceutical is an agent designed to selectively identify and deliver radiation to the tumor site.

Radiopharmaceuticals are composed of three parts: a radioisotope that is protected by a chelator, a targeting ligand and a linker that binds the radioisotope and ligand together.

The radioisotope can be a therapeutic high energy cell-killing one, like Actinium or Lutetium, or a lower energy imaging one, like Gallium, that does not damage cells.

The targeting ligand delivers the radioisotope directly to a specific organ, tissue or cell that expresses the target, while avoiding normal tissues that do not express its target.

The Curie difference

The Curie difference

Curie is driven by tumor target biology, pairing ligand modality to target features. Curie ligands are designed to allow deeper, more homogeneous tumor distribution as well as rapid systemic clearance – to achieve a drug profile that has not yet been achieved with existing modalities.

Macrocyclic peptide-based drug discovery is key to Curie’s strategy for targets with well-defined extracellular domains. In other high value targets that have less well-defined structure or targets that are shed, Curie is employing proprietary peptidic and non-peptidic approaches.

Alongside ligand discovery, Curie’s in-house radiochemistry and radiobiology teams harness alpha and beta radionuclide payloads to build radiopharmaceuticals with the optimal balance of properties from the ground up.

Curie’s ligand design criteria include maximal potency, selectivity, stability, physicochemical multiparameter optimization and avoidance of drug efflux/uptake transporters, alongside addition of linker and chelation chemistry for the radioactive payload. Balancing all of these factors requires Curie’s tried and tested R&D expertise and dexterity in peptide and nonpeptidic small molecule drug discovery.

Drug development engine

Driven by target biology

No one ligand discovery platform is suited to all high value tumor targets. Key aspects of the target biology define selection of the most suitable modality, e.g., the presence or absence of structured extracellular domains, whether the target internalizes, at what rate and whether this is necessary for delivery of the therapeutic payload to the cell. Furthermore, other targets are actively shed into circulation, leaving short “stubs” of membrane-proximal peptides, for which it can be challenging to obtain ligands displaying high affinity and selectivity. The Curie R&D team applies its expertise across a panel of ligand platforms to select the most appropriate modality for the target.

Receptors with structured ECD
Receptors with structured ECD
Receptors lacking a structured ECD
Receptors lacking a structured ECD
Short “stubs” left after shedding
Short “stubs” left after shedding
Curie radio-conjugation platform

Curie radio-conjugation platform

Curie’s in-house radiochemistry and ligand discovery teams work hand-in-hand to deploy well established off the shelf radio-conjugation approaches and to evaluate novel chelation chemistries, to deliver payloads to tumors.

Curie uses both alpha and beta emitting radionuclides to address significant therapeutic needs in solid tumor biology.
Curie ligands allow interchangeability of alpha and beta radionuclides. Radionuclides can manipulate the tumor microenvironment in many ways including ablation and neoantigen production. These effects can be tumor specific, nuclide specific, and duration and dose specific. The desired radiobiology, together with the medical setting, is key to determining choice of payload.

Right drug, right dose, right patient – Theranostic approaches

Radiopharmaceuticals allow patient selection approaches to be embedded in clinical development and subsequent commercialization. The same ligand can be “armed” with a therapeutic radionuclide (thera) or diagnostic / imaging radionuclide (nostic). We utilize a theranostic strategy to confirm target engagement, select patients and optimize dose in clinical development.

Diagnostic radioligand
Therapeutic radioligand