A Technology Platform for Localized Delivery of Medicinal Drugs

Acoustic Cluster Therapy - ACT With experience gained from earlier pre-clinical studies the ACT procedure has been optimized before starting a full scale PoC study in which the effects of two chemotherapeutic agents (paclitaxel and Abraxane) on prostate cancer, treated weekly for four weeks, with and without ACT co-injection, was investigated. Results from this study show a remarkable improvement in drug efficacy with combination with ACT . Compared with Paclitaxel alone, the tumor growth rate was lowered by a factor of approx. 10, all animals receiving ACT responded to treatment and 42% were in stable, complete remission four months after study start. Combining paclitaxel with ACT, the median survival increased approx. 100%. Animals treated with Abraxane alone shows relatively good effect with 0% tumor growth after one month, however, animals treated with Abraxane + ACT showed a reduction in tumor volume of 80%. All animals treated with Abraxane alone relapsed after ended treatment. In combination with ACT, however, all animals went to stable, complete remission after 4-8 weeks and 67% of the animals stayed in this condition until end of study (4 months). The survival fraction in the Abraxane alone group was 0%, v.s. 100% for the Abraxane + ACT group. These studies show a remarkable effect level and the article that presents the results in Journal of Controlled Release was chosen as cover story and editorial comment. Several pre-clinical therapy studies in various models and with various chemotherapeutic agents are now underway to verify and improve the therapeutic effect using ACT. Significant synergistic effects between ACT and Doxil (liposomal doxorubicin) for treatment of triple negative breast cancer have been shown. Doxil alone shows a reasonable effect, with an increase in median survival (vs. saline control) from approx. 20 to approx. 75 days. However, all animals in this group shows regrowth and the survival fraction after 200 days was 0%. In comparison, for the group treated with ACT in combination with Doxil, 63% of the animals were cancer free after 200 days. Strong synergistic effects have also been shown when combining ACT with gemcitabine for treatment of prostate cancer. Gemcitabine alone shows a relatively good effect with an increase in median survival from approx 30 to approx 55 days. However, all the animals in this groups showed regrowth and the survival fraction was 0% after 70 days. In comparison, for the group treated with ACT in combination with gemcitabine, the median survival was 110 days and 50% of the animals were in complete stable remission after 120 days. Studies in relevant models for pancreatic cancer and colon rectal cancer are ongoing. Work to establish ACT procedures for clinical application has been furthered and promising results have been obtained using a regular GE Vivid E9 scanner, which is likely to be used as platform for Phase I/IIa. An supply agreement has been made with GE Healthcare (Oslo) to serve as a Contract Manufacturing Organisation for supply of clinical material. Start clinical trial is now scheduled for late 2018.

The project targets development a novel Phase Shift concept for localized drug delivery, offering a number of unique attributes vs current state of the art technologies, holding a significant potential for solving major healthcare challenges. Phoenix So lutions` unique technology is based on ultrasound mediated release from a two component micro-particle system. Drug loaded oil droplets are mixed with micro bubbles forming micron sized bubble/droplet clusters. After i.v. injection, when exposed to standa rd medical ultrasound at the targeted pathology, the component oil undergo a liquid-to-gas phase shift (vaporization) and the drug load is instantly released into the vascular space. The resulting bubble expands to ~25 µm and transiently (1-3 minutes)bloc ks the microcirculation, keeping the released drug at high concentration and close proximity to the target tissue. Further application of low frequency ultrasound oscillates the bubbles and induces bio-mechanisms that increase the local permeability of th e vasculature, allowing drug delivery into the targeted tissue. The primary objective of the R&D project is to demonstrate Proof of Concept (PoC) in a relevant oncology model; lead product candidate showing 75% improvement in safety/efficacy parameters vs current state of the art therapy regime. A project plan detailing an iterative optimization of formulation/procedures with responses from in-vitro and in-vivo studies has been made. To execute the program Phoenix has partnered with NTNU and Institute o f Cancer Research (UK). Total project cost is ~ 34 million NoK. Post project the lead product candidate from PoC will be brought into further development through formal GLP studies and clinical trials. In addition, use of the technology in other segments of medicinal therapy (e.g. drug delivery to brain tissue) will be explored.