FUS Foundation 3rd Symposium Kicks Off: Relevant Highlights for Celsion Investors to Note

Today marks the official kick-off of the Focused Ultrasound Foundation's (FUS) 3rd international symposium taking place from October 14-17th. The FUS foundation really has been the academic vehicle pushing for the adoption of high-intensity focused ultrasound, and its many applications, both in research and clinical settings. This is relevant for Celsion investors because as many of you know, HIFU truly represents the optimal heating modality with which to pair with temperature-sensitive liposomes such as Celsion's ThermoDox. Celsion has 3 ongoing HIFU clinical programs underway, the most advanced of which is the planned Phase II study examining Philips' Sonalleve MRI-HIFU with ThermoDox for the pain palliation of bone metastases. Other trials include an early stage pancreatic cancer study looking at HIFU and ThermoDox in collaboration with the University of Washington, and a study at Oxford University (currently pending IRB approval)  in liver metastases using ultrasound-guided HIFU plus ThermoDox.

The below program includes all the abstracts and poster sessions for the FUS symposium, and while the entire program is extremely interesting from the perspective of seeing HIFU's clinical utility mature across many indications, I would draw interested Celsion stakeholders to the following pages:

• Page 54 - Differences in Intratumoral Distribution of Doxorubicin Releeased from Temperature-Sensitive Liposomes During Hyperthermia, Ablation and Combined Treatment: Highlights the effect of different heating modalities on the release of doxorubicin from ThermoDox (presumably, though cannot confirm) using HIFU. Of interest for future clinical applications using ThermoDox is the finding that a combination of ablative and mild-hyperthermia are optimal to enhance drug delivery.
• Page 55 - Ultrasound-Triggered Release of Doxorubicin from Thermosensitive Liposomes Modified with Poly Copolymers for Cancer Therapy: Demonstrates a next generation temperature sensitive liposome with a more responsive drug release profile than the comparator "temperature-sensitive liposome (TSL)" product, presumably ThermoDox. This is still very early stage, so from a competitive standpoint, it is not clear how this could affect ThermoDox.
• Page 85 - Phase II Trial Design of MRI-Guided High Intensity Focused Ultrasound and Lyso-thermosensitive Liposomal Doxorubicin for Palliation of Painful Bone Metastases: This is not new, as I have talked about this before, but this will be a nice forum for Celsion to discuss their planned joint PII with Philips. The proof of concept of using MRI-HIFU for bone metastases in general was highlighted on Pages 80-82 (page 80 shows outcome of a multi-center PIII trial amongst patients for whom radiation therapy was contraindicated)
• Page 91 - HIFU Ablation for Hepatocellular Carcinoma: Updated Applications: While this presentation does not address temperature sensitive liposomes in any direct manner, it is nevertheless important since it establishes the use of HIFU, along with HIFU in combination with TACE, for the treatment of HCC. As I mentioned before, it is important for HIFU to establish itself on its own two feet before future applications with ThermoDox begin to take off. The same type of proof was required for radiofrequency ablation for HCC, which is now considered a standard of care in its own right. This is a great step in that direction for the use of HIFU for HCC.
• Page 92 - Magnetic Resonance guided Focused Ultrasound (MRgFUS) Treatment of Primary Pancreatic and Hepatic Cancer: Preliminary Experience in Tumor Control: Same as above, except this goes one step further and examines the use of HIFU for pancreatic cancer as well.
• Page 93 - MR-Guided Focused Ultrasound Induced Hyperthermia for Enhancing Drug Delivery in a Pancreatic Cancer Mouse Model: Note that one of the authors of this study is Joo-Ha Hwang from the University of Washington, and Philips/FUS funded this work. I would venture to say this is directly related to the aforementioned pancreatic cancer HIFU study Celsion announced earlier this year. Using Philips' Sonalleve MRI-HIFU, the study demonstrated strong proof of concept for local drug release from ThermoDox (again, presumably) in a pancreatic cancer mouse model.
• Page 102 - MRI-HIFU Drug Paintbrush: Large Volume, Conformal Mild Hyperthermia with MRI-HIFU Used to Trigger and Monitor Release from Image-Able, Temperature-Sensitive Liposomes: Clearly, this is my favorite potential application of ThermoDox, and it involves Celsion's next generation "4 lipid" version of ThermoDox in which an imaging agent would be combined with the drug to monitor in real-time, uptake of drug using MRI-HIFU. The study shows that lesions of variable shapes can be targeted with MRI-HIFU, and drug release from the "image-able" liposome can be well characterized. This application of ThermDox gets me most excited, I have to say.
• Page 104- Targeted Drug Delivery By Focused Ultrasound Mediated Hyperthermia Combined with Temperature Sensitive Liposomes: Again, this is presumably speaking about ThermoDox, and this somewhat ties back to Page 54 from the above. Using a mathematical model, this study demonstrated that hyperthermia followed by ablative temperatures yielded much more drug from the liposome (40%) compared to mild hyperthermia alone. This has implications for future clinical applications to optimize the delivery of hyperthermia for use with ThermoDox. 

Again, there are a lot of other interesting pieces of data being presented this week pertaining to HIFU, and I only meant to highlight a select few. While my attention remains focused on the HEAT study, it is nevertheless encouraging to see Celsion's technology being used in various applications with HIFU. Let's see how the market reacts to any potential "buzz" coming out of the FUS Foundation 3rd Symposium.

Best,
Siavoche