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Internal pipeline

Nanomedicine for high-grade serous ovarian cancer

Ovarian cancer is usually found late, responds well to platinum chemotherapy the first time, and then comes back resistant. Our programme attacks the second half of that sentence: carriers that reach disseminated peritoneal disease, stay in contact with it, and deliver two agents at once.

Why ovarian cancer needs its own delivery strategy

Advanced epithelial ovarian cancer spreads by shedding cells into the peritoneal cavity, which then seed across the peritoneal surface, the omentum and the bowel serosa as many small implants. There is often no single mass to target and no reliable tumour vasculature to exploit. Ascites dilutes and washes out anything given into the cavity.

  • Most patients present at an advanced stage, with disease already disseminated across the peritoneum.
  • Initial response to platinum–taxane chemotherapy is high, but relapse is the norm rather than the exception.
  • Each subsequent line is less effective as platinum resistance develops, and the resistance mechanisms are plural — drug efflux, altered DNA repair, apoptotic escape.
  • The intraperitoneal route gives direct access to the disease, but only if the carrier stays put long enough to matter.

Nanocarriers already have precedent in this disease: a PEGylated liposomal anthracycline has been in clinical use for recurrent ovarian cancer for years, and a folate-receptor-targeted antibody–drug conjugate has since validated folate receptor alpha as a targetable antigen in this population. Our work sits in the gap between those two ideas.

What a carrier has to do here

  • 01 — Stay in the cavity

    Residence time in the peritoneal space is the first-order variable for intraperitoneal dosing. Size, surface charge and corona density are tuned to slow lymphatic clearance without provoking aggregation in ascitic fluid.

  • 02 — Bind the right cells

    Folate receptor alpha is overexpressed on a large majority of epithelial ovarian tumours and is comparatively scarce on normal tissue, which makes it our primary targeting vector. Ligand density is optimised, not maximised — too much ligand shortens circulation and increases off-target uptake.

  • 03 — Release on cue

    Payload has to stay encapsulated in the cavity and release intracellularly. We use reduction-sensitive platinum(IV) prodrug chemistry so that release is coupled to the intracellular environment rather than to time.

  • 04 — Carry two things at once

    A cytotoxic alone selects for resistance. Every lead programme co-delivers a second agent aimed at the resistance mechanism itself, so both arrive in the same cell at the same time.

Characterisation of the lead formulation

Every batch is characterised for size, dispersity, surface charge, encapsulation efficiency and serum stability before it goes anywhere near a cell.

Hydrodynamic size distribution, BGX-101

Dynamic light scattering, intensity-weighted, 25 °C in PBS

Current lead formulation First-generation prototype
Particle size distribution for the current lead formulation and the first-generation prototype The current lead formulation shows a single narrow peak near 96 nanometres. The first-generation prototype shows a broader, flatter distribution centred near 180 nanometres and extending past 500 nanometres. 96.4 nm 10 30 100 300 1000 HYDRODYNAMIC DIAMETER (nm, log scale) INTENSITY (%)

Z-average diameter

96.4 nm

Polydispersity index

0.087

Zeta potential

−24.3 mV

Encapsulation efficiency

91.2 %

Drug loading

8.4 % w/w

Ligand density

3.1 mol %

Serum stability, 24 h

< 6 % leak

Batch-to-batch CV

4.2 %

Representative values from the current lead batch. Replace with your own release data before publication.

The pipeline

CodeProgrammePayloadRouteStage
BGX-101 FRα-targeted platinum prodrugFolate-decorated PEGylated liposome for platinum-sensitive relapse Pt(IV) prodrug IP / IV
Lead optimisation
BGX-204 Resistance-reversal co-deliveryIonisable lipid nanoparticle carrying siRNA against efflux and repair pathways, co-loaded with a taxane siRNA + taxane IP
Discovery
BGX-310 Peritoneal-retentive micellePLGA–PEG micelle tuned for cavity residence, pairing DNA repair inhibition with innate immune activation PARP inhibitor + STING agonist IP
Discovery
BGX-PLAT Organoid response platformPatient-derived ovarian organoids imaged and scored automatically for carrier uptake and response Enabling platform
In routine use

Programme codes, stages and payload combinations shown here are placeholders for the site build. Swap in your real portfolio before going live.

Models and methods

In vitro

Cell panels

Matched platinum-sensitive and platinum-resistant ovarian lines, screened for folate receptor alpha expression so that targeting effects can be separated from cytotoxicity.

In vitro

3D and organoid

Spheroid penetration assays and patient-derived organoids, imaged over time to measure carrier uptake depth rather than surface binding alone.

In vivo

Orthotopic models

Intraperitoneal xenograft models with bioluminescent readout, which reproduce disseminated peritoneal disease far better than a subcutaneous flank tumour.

Analysis

Biodistribution

Fluorescently labelled carriers tracked across organs and implants, then quantified section by section using our own image analysis pipeline.

Analysis

Tissue quantification

Implant-level penetration depth, per-cell payload signal, proliferation and apoptosis indices, and immune infiltration — the same service we sell to clients.

Analysis

Formulation QC

DLS, zeta potential, cryo-electron microscopy, HPLC quantification of loading, and stability testing in serum and in ascitic fluid.

What we have not solved yet

  • The protein corona

    Proteins adsorb onto any nanoparticle within seconds of contact with biological fluid, and can mask the targeting ligand entirely. We measure corona composition in ascitic fluid rather than assuming buffer behaviour carries over.

  • Enhanced permeability is unreliable

    Passive accumulation through leaky vasculature varies enormously between tumours, models and patients. We treat it as a bonus, not a mechanism, and design for active targeting and direct cavity access instead.

  • Mononuclear phagocyte clearance

    A large fraction of an intravenous nanoparticle dose is taken up by liver and spleen macrophages. Intraperitoneal dosing reduces but does not remove the problem.

  • Scale-up

    Formulations that behave beautifully at bench scale frequently do not survive the move to microfluidic manufacture at clinical volumes. We characterise batch-to-batch variability early rather than discovering it during IND-enabling work.

Ways to work with the programme

Route 01

Research collaboration

Joint work on targeting chemistry, resistance biology, or peritoneal pharmacokinetics, with agreed publication and IP terms up front.

Route 02

Clinical partnership

Access to annotated ovarian tissue and organoids, and collaboration on translational endpoints for later-stage studies.

Route 03

Grant consortium

We participate in UK and European funding consortia as the formulation and quantitative imaging partner.

Working on the same disease?

We would rather compare notes than duplicate a failed experiment. Collaboration enquiries go straight to the research team.