Molecularly targeted therapies directed at molecules or receptors characteristic of cancer cells are widely used in oncology.

If a target molecule is also expressed on healthy cells, however, treatment may affect healthy tissue.

Biozipcode™ cell-targeting technology aims to look beyond a single molecular marker and use

cell-surface features
＋
the tissue environment
＋
binding selectivity in the body

to distinguish cancer cells and tumor tissue at the cellular level.

We are studying this as an added layer of targeting that addresses which cells receive treatment alongside existing molecularly targeted approaches.

Biozipcode™ research uses a large library, primarily of short peptides, to search for sequences that bind to specific cells or tissues.

For a sequence of seven amino acids, there are

20⁷ ≒ 1.28 billion possibilities

from which to select candidates.

We look for sequences that

bind to tumors
while
binding as little as possible to healthy tissue

for further evaluation.

Biozipcode™ is not the name of a single peptide; it is a cell-targeting platform for finding distinct sequences for different target cells and tissues.

Research materials compare sequences detected in pancreatic and liver cancer models and examine candidate sequences found in both tumors.

If peptides that bind reproducibly across multiple cancer types while showing limited binding to healthy tissue can be confirmed, this work could lead to targeting technology applicable to a broader range of tumors.

However, no Biozipcode™ sequence shared by all cancers has been established.

Further validation is needed across cancer types, patients, and cell populations within tumors.

Finding a peptide that binds to a tumor is not the endpoint of Biozipcode™ research.

Developing a therapeutic approach requires the following stages:

Tumor Binding
↓
Target Validation
↓
Payload Conjugation
↓
Tumor Delivery
↓
Therapeutic Effect

Each stage requires further work.

Research materials also discuss testing a candidate pancreatic cancer-binding peptide combined with a cytotoxic peptide, as part of efforts to translate targeting into treatment.

A central goal of cell-targeting technology is to concentrate a drug in cancer cells and reduce exposure in healthy tissue.

If a sufficiently selective Biozipcode™ sequence can be established, it may support

• greater drug accumulation in tumors
• less exposure in healthy tissue
• optimized dosing
• an improved therapeutic index

for a particular candidate.

Biozipcode™ does not imply a treatment free of all adverse effects.

Safety must be evaluated for each candidate, taking into account

• the peptide
• the target
• Payload
• Vehicle
• dose
• route of administration
• biodistribution

and other factors.

Efficient delivery to the intended cells is a major challenge for genes and nucleic acid therapeutics such as siRNA.

The research underlying Biozipcode™ has previously explored nervous-system targets, including:

• DRG-targeted gene delivery
• spinal cord-homing peptides
• microglia-targeted siRNA delivery

among other approaches.

We aim to extend this approach to cancer by combining

cancer-cell-binding peptides ＋ gene or nucleic acid therapeutics

as a potential new form of targeted therapy.

Biozipcode™ sequences that selectively bind cancer cells could also have diagnostic applications.

Potential uses include:

• tumor tissue labeling
• cell and tissue staining
• cancer cell capture
• imaging
• support for pathology assessment
• monitoring treatment response

among other possibilities.

We aim to use the same targeting peptide for both

Detection
and
Delivery

to connect diagnosis and treatment.

A major challenge in developing cell-targeted oncology therapeutics is tumor heterogeneity.

Even within one tumor in the same patient, cancer cells do not necessarily share the same features.

Cell-surface characteristics may also vary between

• primary tumors
• metastases
• before treatment
• after treatment
• drug-resistant cells

and other settings.

We therefore do not assume that one Biozipcode™ sequence can recognize every cancer cell. Research may need to evaluate multiple candidate peptides and combinations of targets.

Current findings include preclinical research in mouse models implanted with human cancer cell lines.

Cancers in patients can differ in

• genetic background
• tumor microenvironment
• cancer type
• disease stage
• treatment history
• tumor heterogeneity

and other factors.

We therefore need to test the selectivity of Biozipcode™ candidates in human material, including

• patient-derived cancer cells
• surgical and biopsy specimens
• organoids
• patient-derived xenograft
• comparisons with healthy tissue

to assess selectivity in humans.

This pipeline is at the DISCOVERY / PRECLINICAL RESEARCH stage.

Work to date includes candidate peptide discovery in cancer models, NGS sequence analysis, comparisons with healthy tissue, and binding assays using synthetic peptides.

Next, it will be important to assess

reproducibility of candidate sequences
↓
validation in patient-derived tumors
↓
combination with a payload
↓
efficacy and safety

for each candidate.