Pipeline

Primary liver cancer is the second most common cause of cancer-related deaths worldwide. The global incidence of primary hepatocellular carcinoma (HCC) has been rising over the last 25 years and is set to increase further in many countries^[1]. Around 70% of patients are unresectable and unsuitable for a liver transplant on presentation^[2].

Additionally, 25–30% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases, with only around a quarter of these patients deemed suitable for potentially curative surgical resection^[3].

External beam radiotherapy (SBRT or PBRT) is not recommended as a first-line treatment option. Current first-line loco-regional treatment options, such as Microwave Ablation (MWA) and Trans-Arterial Radioembolisation (TARE), have significant technical, medical and anatomical limitations. As a result, around ~40% of patients experience disease progression 3-5 years after treatment, representing a major unmet clinical need^{[4],[5],[6],[7]}.
YntraDose can be used to treat many patients that are not suitable for MWA or TARE, and does not require general anaesthesia. It is not dependent on intravascular administration, which may be particularly advantageous in the treatment of poorly vascularised liver tumours.

The highly localized nature of YntraDose removes the risk of off-target effects, and it can be used to treat tumours close to delicate structures that would be damaged by other approaches. Furthermore, the ablation zone can be assessed within the same treatment session, avoiding the need for return visits and giving more confidence in the therapy.

In an ICH-GCP and ISO14155 compliant clinical investigation, YntraDose has been shown to be safe and well tolerated in a range of unresectable HCC patients. Furthermore, very encouraging effectiveness outcomes at just day 21 post-treatment with YntraDose have been observed. In this setting YntraDose was administered percutaneously directly into the liver lesions under radiological guidance.

Preliminary results from this study were presented as a poster at the GEST 2023 meeting in May 2023 and have subsequently been published as an abstract^[8].

PDAC has the worst outlook of any form of cancer in terms of progression-free and overall survival, and is the seventh most common cause of cancer related death worldwide. Around thirty percent of PDAC patients present as locally-advanced^[1].

The first-line treatment options in this setting are mainly systemic chemotherapy such as FOLFIRINOX (FFX, a four-drug cocktail) or Gemcitabine + Nab-Paclitaxel (GN) combination therapy. Median overall survival (mOS) is less than 18 months with either regimen^[2], representing a population with high unmet medical need.

External beam radiotherapy can be employed for those patients no longer responding to chemotherapy, however there is no strong clinical evidence of its effectiveness and this is thought to be due to the fact that only relatively low doses of radiation can be used due to the off-target effects on surrounding tissue structures.

ESMO international guidelines actively promote the development of new therapeutic options for this patient group. YntraDose is well placed to become the alternative treatment that is so urgently needed.

Unlike systemically administered Radioligand Therapy (RLT), YntraDose can impart a relatively high locally-administered dose of radiation from within the tumour(s). The use of these two radiotherapeutic approaches could provide a powerful combination.

The beta radiation emitted by YntraDose’s yttrium-90 microspheres damages cancer cells, triggering an inflammatory and immunogenic response. It is well established that immunotherapy agents, such as checkpoint inhibitors, can boost this immune response and synergistically enhance the effects of radiotherapy.

BetaGlue is interested to collaborate and partner its YntraDose platform with therapeutic agents where there is synergistic potential. Contact us.