A biopsy-guided VHH nanobody targeting platform that phenotypes each patient's tumor, selects the matched nanobodies from a curated library, and delivers a personalized therapy prescription. The targeting intelligence is payload-agnostic — built for radioligand therapy today, and any precision oncology payload tomorrow.
A nanobody is the smallest naturally occurring antigen-binding fragment known in biology. Discovered in 1993 in camelid blood, it is the variable domain of a heavy-chain-only antibody — a single protein domain that does the full job of a conventional antibody's two-chain binding arm, at one-tenth the size.
That size difference is not cosmetic. It fundamentally changes what's possible in cancer imaging and therapy.
Click each to compare // CDR3 loop shown in teal enables hidden epitope access
In 1993, researchers discovered that camelids — llamas, camels, and dromedaries — naturally produce a unique class of antibody found nowhere else in nature: heavy-chain-only antibodies (HCAbs). Unlike conventional antibodies, these have no light chains. Their single variable domain (the VHH) does all the binding work alone — at one-tenth the size of a conventional antibody. HelioKrystos harnesses this gift — a molecular tool placed in nature long before we knew we would need it — using phage display to build a biopsy-guided VHH target library against cancer targets — in development, to be built with a development partner.
Click each step to see how the HelioKrystos platform is designed to work from first sample to final prescription. Image it, measure it, treat it.
A standard core needle biopsy of the patient's tumor is obtained — the same procedure already used in clinical oncology workup. No additional invasive procedure is required beyond standard-of-care tissue sampling.
In the HelioKrystos workflow, the biopsy is phenotyped to return a molecular map: which tumor-associated antigens are expressed, and at what level.
The biopsy expression profile is matched against a biopsy-guided VHH target library — in development, to be built with a development partner. The best-fit nanobody for the patient's expressed antigen is selected for that individual.
Once the library is built and validated, no de novo nanobody discovery would be required for each patient. That is what is designed to make the workflow clinically scalable.
The biopsy-selected nanobody — matched to that patient's antigen expression profile — is radiolabeled directly with a PET isotope and imaged with standard PET/CT. Nanobody tracers offer rapid tumor uptake and fast blood clearance, which support low background signal and high tumor-to-background contrast.
The imaging step is designed to confirm in vivo target engagement and quantify uptake per lesion — the biological basis for the therapy prescription that follows. Image it first.
The quantitative PET data — antigen density per lesion, pharmacokinetic curves, organ uptake — is designed to feed the HelioKrystos dosimetry engine (in development). Using absorbed dose modeling (MIRD formalism + Monte Carlo), the goal is to calculate the therapeutic activity needed to deliver a tumoricidal dose while staying within organ tolerance limits. Measure it.
For therapy, the same matched nanobody is given in a pretargeted form: it localizes to the tumor first, then a separately given ¹⁷⁷Lu payload clicks to it there, limiting kidney dose — in a personalized activity prescription unique to that patient's tumor biology. Treat it.
The HelioReport is the planned clinical deliverable — a structured, oncologist-facing document summarizing the patient's complete tumor antigen expression profile, PET imaging findings, and a personalized therapy prescription with individualized payload and dosing guidance.
Think of it as the Foundation Medicine genomic report, but for targeted drug delivery: a molecular portrait of the tumor that directly translates into an actionable, individualized treatment plan — whether the payload is a radionuclide, a cytotoxin, or a future therapeutic.
VHH genes from immunized camelids are cloned into phagemid vectors, generating diverse libraries of binders displayed on phage surface proteins. Iterative panning against recombinant tumor antigens enriches for high-affinity, radiolabeling-compatible binders. The HelioKrystos biopsy-guided VHH target library is in development, to be built with a development partner.
Molecular BiologyRadiolabeled VHH nanobodies offer a favorable imaging profile: rapid tumor uptake driven by high-affinity binding, fast renal clearance due to the ~15 kDa size, and same-day imaging capability. These properties — well-established in the nanobody imaging literature — produce high tumor-to-background contrast and enable per-lesion quantification of target antigen engagement in vivo.
Nuclear MedicineVHH nanobodies can be site-specifically modified through an engineered C-terminal handle. For imaging, the nanobody is labeled directly with standard PET radionuclides, which suit its fast kinetics. For therapy, HelioKrystos uses pretargeting: the nanobody goes first, and ¹⁷⁷Lu (β⁻ emitter, t½ 6.7 days) follows on a small partner molecule that clicks to it at the tumor. Alpha-emitter payloads are a future direction.
RadiochemistryPatient tumor biopsy undergoes IHC panel staining against a panel of tumor-associated antigens, generating a semi-quantitative expression score (H-score) per target, with proteomic confirmation. The resulting expression profile is designed to drive nanobody selection from a biopsy-guided VHH target library — in development, to be built with a development partner.
Pathology · ProteomicsThe platform is target-agnostic: one delivery approach is designed to pair with VHH binders against many cell-surface targets across tumor types. Specific targets will be prioritized with a development partner as the biopsy-guided VHH target library is built.
Oncology · StrategyPost-imaging dosimetry is designed to use MIRD (Medical Internal Radiation Dose) formalism incorporating patient-specific PET-derived organ uptake and tumor pharmacokinetics. Monte Carlo simulation of radionuclide transport provides absorbed dose estimates per lesion and per organ-at-risk. The goal is a patient-specific therapeutic activity in GBq — not a protocol default.
Medical PhysicsDr. Magnusson is a Nuclear Medicine physician trained at the University of Wisconsin, with direct clinical experience administering radioligand therapy including ¹⁷⁷Lu-PSMA and ¹⁷⁷Lu-DOTATATE. He founded HelioKrystos out of a straightforward conviction: patients deserve better outcomes and a better treatment experience than current protocols can offer.
HelioKrystos emerged from the clinical reality of watching cancer patients struggle with the toxicity of systemic chemotherapy. This platform provides a scaffolding for precision oncology — delivering therapy to where it's needed, sparing the rest — with the goal of better outcomes and a more positive experience for patients.
HelioKrystos is building a target-agnostic, nanobody-based targeted drug delivery platform — guided by patient biopsy, beginning with radioligand imaging and therapy, and modular for future payloads. The biopsy-guided VHH target library is in development and is the piece we aim to build with a development partner. We welcome conversations with strategic development partners, oncology-focused angels, and life science seed funds.