Pipeline

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 chemotherapies and is called neoadjuvant treatment.

External beam radiotherapy can be employed for those patients both for no longer responding to chemotherapy or combined with Chemotherapy in the neoadjuvant treatment approach.

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

The incidence of primary hepatocellular carcinoma (HCC) has been rising worldwide over the last 25 years and is expected to increase until 2030 in some countries including the United States. In 2018, primary liver cancer represented the fifth most common cancer in men and the ninth in women and the second most common cause of cancer-related death worldwide ^[1]. Around 70% of patients are deemed unresectable and not suitable for transplant on presentation ^[2] and external beam radiation (both ‘SBRT’ and ‘PBRT’) are not recommended as first-line treatment options in this setting by the international guidelines.

Colorectal cancer (CRC) is a leading cause of cancer-associated death in Western populations and the third most frequent cause of cancer-related death worldwide. Population-based studies have shown that around 25–30% of patients diagnosed with CRC develop liver metastases during the course of their disease. Indications for curative-intended treatment of CRC liver metastases (CRCLM) have expanded in recent years. Unfortunately, despite the oncological and surgical advances made, only about 25% of patients affected are amenable to resection, which is regarded as the only way to achieve a cure. Historically, the indication for resection of liver metastases was based on tumour-related factors, for example tumour number, size and distribution in the liver. Currently, however, focus is placed on ‘Future Liver Remnant’ (FLR), with resectability defined as the ability to perform a complete (R0) resection, while preserving a sufficient FLR. The presence of unresectable extra-hepatic disease is still considered a contraindication to liver surgery. Liver resection can achieve 5-year survival rates of above 50%, compared to only around 5% for patients treated with palliative intent ^[3].

For these unresectable patients, a range of first-line loco-regional treatment options exist, each with advantages and limitations. The most prominent are Microwave Ablation (MWA), and transcatheter radiotherapy by Trans-Arterial Radioembolisation (TARE). Sadly, the reported Local Tumour Progression (LTP) rates for MWA and TARE are ~40% 3-5years post-administration ^{[4, 5, 6, 7]} representing a major unmet clinical need.

YntraDose is well positioned relative to these approaches because YntraDose is not dependent on intravascular administration which may be particularly advantageous in the treatment of poorly vascularised CRCLM. YntraDose can be used to treat many of the patients deemed ineligible to MWA and/or TARE. Moreover, the key limitations thought to contribute to the high recurrence rates are addressed by YntraDose such as no off-target radiation, the ability to treat lesions proximal to delicate structures, no need for general anaesthesia and the ability of the Interventional Radiologist to assess a predictable ablation zone within the same treatment session.

The incidence of Ductal Carcinoma In Situ (‘DCIS’ or Stage 0 disease) markedly increased from 5.8 per 100,000 women in the 1970s to 32.5 per 100,000 women in 2004 and has since reached a plateau. Around 25% of breast cancers diagnosed in the United States are DCIS, and 55,720 new cases have been reported in 2023. This increase is attributed primarily to the utilization of breast cancer screening by mammography ^[1].

According to ESMO Guidelines Breast Cancer Surgery with post-operative RT is the preferred local treatment option for the majority of patients with early breast cancer ^[2].
There is an opportunity for YntraDose to provide an alternative to Intra-Operative Radiotherapy (IORT) and post-surgery SBRT for the effective treatment of surgical margins. YntraDose can be directly implanted into the tumour bed following tissue conserving lumpectomy prior to surgically closing the patient.

YntraDopse can confer several advantages over IORT or EBRT in this setting, including reduced patient visits, improved patient compliance, no capital equipment and operational and resource efficiency savings for healthcare providers.

Over 1,000 peer reviewed publications report the opportunity of the synergistic effect of radiotherapy and immune-oncology agents. The effect of sufficient levels of beta radiation on tissue is an inflammatory and immunogenic response followed by subsequent coagulative necrosis. The combination of inflammation and the immunogenic effect of beta radiation combined with an immune-oncology agent to synergistically acts to ‘unstealth’ the tumour region and stimulate an immune response. BetaGlue Therapeutics is pursuing the evaluation of this potentially powerful combination broadening the platform capability of YntraDose even further.