PROJECT SUMMARY
Diffuse Intrinsic Pontine Gliomas (DIPG) are rare and deadly pediatric brain tumors. They are extremely
aggressive tumors that are found in the pons, which controls many of the body's most vital functions such as
breathing, blood pressure, and heart rate. There is no currently effective means of treatment for DIPG, and the
median survival is 7-11 months after diagnosis. Thus, there is significant need for a method to effectively treat
DIPG. To address this unmet need, SonALAsense is developing sonodynamic therapy (SDT), a non-invasive
drug-device combination, to treat DIPG. SDT uses an MRI-Guided Focused Ultrasound (MRgFUS) device in
combination with a drug called 5-aminolevulinic acid (ALA; SONALA-001). Three independent laboratories have
demonstrated the safety and efficacy of ALA SDT in animal glioma models where the animals were dosed first
with ALA and then treated with MRgFUS at energies that do not raise brain temperature. MRgFUS activated
Protoporphyrin IX (PpIX), a metabolite of ALA, created singlet oxygen that induced necrosis and apoptosis in
the glioma in a process similar to photodynamic therapy. Activation of PpIX non-invasively caused regression of
the gliomas and extended survival. We also have data that support that ALA SDT is safe and well-tolerated in
adult patients with recurrent glioblastoma multiforme, and leads to targeted oxidative stress and accompanying
apoptosis in tumor tissue, in the absence of a thermal effect, similar to the animal model results. SONALA-001
is Orphan Drug designated for the treatment of all malignant gliomas and an Investigational New Drug (IND)
application was cleared to proceed by the FDA. The goal of this R01 is to execute a Phase 2 clinical trial to
provide safety and efficacy data for subsequent trials of ALA SDT in DIPG. As one of three clinical trial sites
participating in this trial, the Ivy Brain Tumor Center will enroll 12 DIPG patients in up to 9 cohorts. This trial will
be uncontrolled for ethical reasons. First, we will determine blood plasma PK of ALA metabolism and PpIX
synthesis as this is the first intravenous (IV) formulation of ALA. Second, we will determine the maximum
tolerated dose (MTD) or recommended Phase 2 dose of MRgFUS energy combined with IV ALA. Third, we will
determine safety and efficacy of ALA SDT by following patients for up to 12 months. Successful completion of
this trial will identify a safe dose to proceed to the next stage of clinical development, in which DIPG patients will
receive SDT therapy on a monthly basis to attempt to maximize effects on survival of these patients using a safe
IV dose of ALA in combination with an optimal dose of MRgFUS. The goal of this development program is to
obtain the clinical data necessary for FDA marketing approval and to commercialize this combination therapy for
DIPG patients who have no therapeutic options. ALA SDT has the potential to be the first successful treatment
for DIPG and for the first time in medical history parents of children with DIPG would not only have hope that the
life of their child could be extended, but also the comfort that the combination therapy used is noninvasive and
has extremely tolerable side effects.
