Key Points
- Advanced Microbubbles is designing and manufacturing custom, size-isolated, ultrasound-triggered microbubbles for drug delivery and gene therapy.
- The company’s vision is to enable safe and precise cancer chemotherapy using uniform-sized microbubbles.
- Promising preclinical research suggests that the use of the company’s microbubbles may help control high-risk neuroblastoma.
Advanced Microbubbles, a relatively new company based in California, is designing and manufacturing custom, size-isolated, ultrasound-triggered microbubbles for drug delivery and gene therapy. With a vision of enabling safe and precise cancer chemotherapy using uniform-sized microbubbles, the company is seeking to solve problems such as poor drug uptake into tumors, off-target chemotoxicity, and serious side effects. Early preclinical research suggests that the use of the company’s microbubbles may help control high-risk neuroblastoma – a tumor that forms in the adrenal glands – using very low drug doses that mitigate drug side-effects.
We spoke with the company’s co-founder and CEO, Jameel Feshitan, PhD, to learn about these innovative microbubbles and the group’s goals to transform focused ultrasound research and clinical care.
When was the company founded and where is it located?
Advanced Microbubbles, Inc. was founded in 2020. It is based in Newark, California.
How did the company get its start?
We were selected for the IndieBio premier accelerator program. Their program provides start-up companies with $250,000 in funding plus access to mentors and investors to help launch new ideas. IndieBio was critical in helping us build awareness and providing a catalyst to move toward proof-of-concept. See Dr. Feshitan Present at IndieBio >
Tell us about your company structure: ownership, lead executives, and their roles.
The company was founded by myself and two of my colleagues, Connor Slagle and Shashank Sirsi, PhD.
Jameel Feshitan, PhD
I have more than 11 years of experience developing size-isolated microbubbles (SIMBs) for ultrasound-targeted drug delivery and diagnostic imaging. I earned my PhD in chemical engineering at Columbia University in 2012 and completed my postdoctoral research at the University of Colorado, Boulder.
Connor Slagle
Connor Slagle is the company’s Chief Technology Officer. He studied chemical engineering and environmental engineering at the University of Colorado, Boulder, and brings biomedical engineering expertise from one of the top microbubble technology laboratories in the world.
Shashank Sirsi, PhD
Shashank Sirsi, PhD, is our Chief Science Officer and an Assistant Professor in the Department of Biomedical Engineering at the University of Texas, Dallas (UT Dallas). He earned his PhD in biomedical engineering at Drexel University and studied microbubbles for drug delivery, 2D- and 3D-ultrasound imaging, and tissue scaffolds at Columbia University. Dr. Sirsi has developed advanced methods of quantitative perfusion imaging in tumors for image-guided drug delivery and developed microbubbles for in vivo monitoring of tumor perfusion, in vivo molecular imaging, and ultrasound-guided drug delivery to solid tumors.
Tell us about your products.
Our primary products are stable, SIMBs that are optimized for ultrasound targeted drug delivery and surgery. Being able to control the size of the microbubble allows researchers to tune the desired level of treatment. For example, we previously collaborated with one of the focused ultrasound companies to discover that the smaller size class –the two-micron size – was better for tumor ablation with focused ultrasound. And a larger size – the four-micron size – was better for targeted drug delivery. That gives our customers the flexibility to pick and choose size based on the desired application. It is an attractive feature for potential partners, and it allows us to create layers of pipeline products for future development and clinical adoption in solid tumor cancer treatment.
What impact will your microbubbles have on the field?
The microbubbles on the market today have traditionally been used for diagnostics – and for that application, the size consistency does not really matter. However, when researchers use diagnostic microbubbles to investigate how they interact with focused ultrasound, we have found issues with performance and consistency.
When administered without microbubbles, standard drug therapies create two types of complications for patients: The first is poor drug penetration, because the tumor barrier or blood-brain barrier (BBB) prohibits the molecules from reaching their target. Secondly, high doses of chemotherapeutics and radiotherapy cause systemic toxicity and serious side effects. For example, young patients with high-risk neuroblastoma face a mortality rate of about 50%. That is down in recent years from 90%, but only because doctors have been forced to increase the amount of chemotherapy and radiotherapy to the point that the children suffer with the side effects for the rest of their lives. The effects range from bone malformations to infertility and secondary cancers. A targeted therapy is needed, which is one reason why we have chosen to pursue this indication to demonstrate the effectiveness of our approach.
Advanced Microbubbles is developing a technology platform that is intended to solve these problems. We have made the holy grail of microbubble engineering – a bubble that is uniform in size and stable so, when combined with focused ultrasound, it can improve the penetration of drugs into the tumor and also allow for precision drug delivery. Our product also allows the use of low doses that can treat the tumor while mitigating the side effects to the patient.
Tell us about your research to date.
We completed a preclinical study in collaboration with the National Institutes of Health (NIH) wherein we delivered the EGFP gene across the BBB. This study was published in Theranostics.
More recently, in collaboration with Dr. Sirsi at UT Dallas School of Medicine, we delivered a large nanoparticle chemotherapy liposomal doxorubicin (L-DOX) into a high-risk neuroblastoma tumor mouse model. Delivering the drug alone produces lower tumor penetration, but our SIMBs with focused ultrasound significantly increase drug penetration into the tumor. Our studies also demonstrate tumor growth reduction as compared with the control group. Crucially, as compared to control groups, our approach enabled L-DOX efficacy at a 25-fold lower dosage without causing any of the typical full-dose chemotherapy side-effects to the specimen, such as loss of motor function, weight loss, or hair loss.
Another study in collaboration with Dr. Sirsi’s laboratory used our bubbles to deliver messenger RNA (mRNA) and plasmid DNA to neuroblastoma tumors.
Do you have plans for clinical trials?
Yes, we are working toward clinical trials. Because microbubbles are currently only approved for diagnostic imaging, we are in discussions with the US Food and Drug Administration (FDA) regarding filing an Investigational New Drug (IND) application to use microbubbles for improving safety and efficacy of anticancer drug delivery. An IND is a request for FDA authorization to administer an investigational drug to humans.
Our plan is to pursue multiple solid tumor cancer indications, starting with neuroblastoma – a pediatric orphan (rare) disease – and expand into pancreatic cancer and glioblastoma via the 505(b)(2) FDA pathway. Neuroblastoma allows us to take advantage of the orphan drug pathway. We intend to demonstrate that the combination of ultrasound and SIMBs is a breakthrough method for improving the efficacy and safety of existing FDA-approved chemotherapies (like doxorubicin or gemcitabine) for treatment of solid tumor cancers. The 505(b)(2) strategy allows us to leverage the established safety data of the FDA-approved chemotherapies to expedite the timeline to get our technology into market.
Can researchers use your microbubbles now?
Yes, absolutely. We have had researchers from across the US and the globe requesting for our SIMBs. We manufacture the bubbles in an incubator facility in the Bay Area and ship them out via FedEx overnight. We have an incredibly efficient production process, and we can make the microbubbles at scale and at high yields. We are easily meeting the demands for research use, and we have plans to scale up for clinical use.
Do you partner with other companies?
Yes, we received a letter of support from CarThera this year for clinical adoption of our microbubbles.
What is next for Advanced Microbubbles?
We are currently trying to raise a Series A funding round of $10 million. That will help fund the IND and take us to the point where we can perform Phase I clinical trials. From there, we hope to be able to expedite approval with the FDA within six years’ time via the rare disease and 505(b)(2) pathway.
What else would you like the community to know?
There are so many diverse studies looking at different indications like brain cancer, pancreatic cancer, etc., and we want to make sure that researchers have access to the right kind of microbubble agents for the style of study. For a long time, the field has been preoccupied with perfecting the focused ultrasound machines, but without the appropriate type of microbubble, the combination therapies will not achieve the desired results. Both components are important.
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