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].

The incidence of Ductal Carcinoma In Situ (‘DCIS’ or Stage 0 disease) increased five-fold from the 1970s to the 2000s (5.8 to 32.5 per 100,000 women), primarily due to increased use of breast screening. Around 25% of breast cancers diagnosed in the United States are DCIS, adding up to more than 55,000 women every year^[1].

Current treatment often includes external beam radiotherapy (SBRT), either delivered intra-operatively or after surgery, with post-operative radiotherapy the preferred option for the majority of patients with early-stage breast cancer^[2].

YntraDose can be directly implanted into the tumour bed following tissue-conserving lumpectomy during the course of the operation. This confers several advantages over external radiotherapy, including reduced patient visits, improved patient compliance, no capital equipment and operational and resource efficiency savings for healthcare providers.

Ongoing evaluation of the safety profile of YntraDose in 13 patients have shown YntraDose to be safe and well tolerated. Preliminary effectiveness and safety data will be analysed by a Data Monitoring Committee in due course.

Lung cancer is the leading cause of cancer mortality worldwide with around 1.8 million lung cancer related deaths reported in 2020 by the World Health Organisation (WHO). Furthermore, around 25% of patients with advanced colorectal cancer (CRC) will experience lung metastases.

For patients where surgery is not an option, loco-regional therapies such as thermal ablation techniques (radio frequency ablation and microwave ablation) may be suitable. However, these approaches carry significant limitations including an inability to treat near large vessels or the pulmonary hilum. There is also a high risk of developing bronchopulmonary fistulas, possibly due to higher temperatures during the procedure^[1].

As a result, nearly one in five patients (18.8%) with tumors ≤ 2 cm will experience local disease progression within 3 years of treatment.
SBRT is another alternative treatment option, but risks major complications including radiation pneumonitis, heart failure, myocardial infarction, bronchial necrosis, and rib fracture^[2].

By offering a highly localized, targeted alternative to thermal ablation or external radiotherapy, YntraDose could reduce the risk of side effects and improve disease control.

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 a quarter (27.5%) of PDAC patients present as locally advanced and borderline resectable^[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 (SBRT/PBRT) is rarely used due to the high risk of off-target damage resulting from the deep-seated location of the pancreas and internal organ movement.

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.

We are evaluating the effects of this potentially powerful combination, which would broaden the platform capability of YntraDose even further.