ALA sonodynamic therapy / INSIGHTEC, SonALAsense, Ivy Brain Tumor Center - LARVOL DELTA

Study of Sonodynamic Therapy in Participants with Recurrent High-Grade Glioma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Dec 2025 ➔ Mar 2028 | Trial primary completion date: Jun 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Solid Tumor

Study of Sonodynamic Therapy in Participants with Recurrent High-Grade Glioma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Solid Tumor • CASP3

Sonodynamic therapy (SDT) using intravenous 5-aminolevulinic acid with non-ablative focused ultrasound for the treatment of diffuse intrinsic pontine gliomas in pediatrics: initial safety and outcomes the multicenter SDT-201 trial (SNO 2024) - P2 | "MRgFUS was combined with the prodrug SONALA-001 (5-ALA iv) to activate its metabolite, protoporphyrin IX, and thereby induce apoptosis within tumor cells...Preliminary analysis of twelve pediatric patients treated with SDT for DIPG demonstrates acceptable safety outcomes and promising clinical results. Additional patient enrollment and longer follow-up times are required to determine efficacy."

Clinical • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

A Phase 1/2 dose escalation and expansion study of sonodynamic therapy with SONALA-001 in combination with non-ablative MR-guided focused ultrasound in subjects with progressive or recurrent glioblastoma (SNO 2024) - No abstract available

Clinical • Combination therapy • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A Phase 2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Patients with DIPG (clinicaltrials.gov) - P2 | N=15 | Suspended | Sponsor: SonALAsense, Inc. | Trial completion date: Jul 2024 ➔ Oct 2024 | Terminated ➔ Suspended

Combination therapy • Trial completion date • Trial suspension • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

A Phase 2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Patients With DIPG (clinicaltrials.gov) - P2 | N=15 | Terminated | Sponsor: SonALAsense, Inc. | N=40 ➔ 15 | Trial completion date: Aug 2025 ➔ Jul 2024 | Active, not recruiting ➔ Terminated; The study is terminated due to lack of funding but not due to safety concerns.

Combination therapy • Enrollment change • Trial completion date • Trial termination • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

A Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Subjects With Recurrent GBM (clinicaltrials.gov) - P1/2 | N=8 | Terminated | Sponsor: SonALAsense, Inc. | Trial completion date: Nov 2026 ➔ Jul 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Apr 2026 ➔ Jun 2024; Study is terminated due to funding challenges and not due to safety concerns.

Combination therapy • Trial completion date • Trial primary completion date • Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A Phase 2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Patients With DIPG (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: SonALAsense, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Interim clinical, pharmacokinetic, and technical report of a phase 2 study of sonodynamic therapy (SDT) using SONALA-001 together with MR-guided low-intensity focused ultrasound (MRgFUS) in children with diffuse intrinsic pontine glioma (DIPG) (ISPNO 2024) - P2 | "SDT is an innovative and to-date well-tolerated strategy for children with DIPG post-initial radiotherapy. Sonications did not result in any adverse procedural effects. SONALA-001 exhibits rapid distribution and clearance, while PpIX PK align with metabolite formation."

Clinical • P2 data • PK/PD data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

A phase 1/2 dose escalation and expansion study of sonodynamic therapy with SONALA-001 in combination with Exablate 4000 Type 2.0 MR-guided focused ultrasound in patients with progressive or recurrent glioblastoma (rGBM). (ASCO 2024) - P1, P1/2 | "Endpoints of this study are safety evaluation, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and determination of pharmacokinetic (PK) parameters. The Phase 2 portion will further characterize safety of RP2D along with evaluation of efficacy with PFS6 (mRANO), ORR, CBR, DOR, DOCR, TTR, and OS."

Clinical • Combination therapy • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Interim report of a phase 2 study of sonodynamic therapy (SDT) using SONALA-001 together with MR-guided low-intensity focused ultrasound (MRgFUS) in children with diffuse intrinsic pontine glioma (DIPG). (ASCO 2024) - P2 | "SDT is a well-tolerated strategy for patients with DIPG after initial radiotherapy. SONALA-001 shows rapid distribution and clearance, and PpIX PK align with metabolite formation. Following dose escalation completion, dose-expansion will be initiated at RP2D offering further insights into safety, PK, and efficacy."

Clinical • P2 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Study of Sonodynamic Therapy in Participants With Recurrent High-Grade Glioma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CASP3

Theranostic Uses of the Heme Pathway in Neuro-Oncology: Protoporphyrin IX (PpIX) and Its Journey from Photodynamic Therapy (PDT) through Photodynamic Diagnosis (PDD) to Sonodynamic Therapy (SDT). (PubMed, Cancers (Basel)) - "This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described."

Journal • Review • Bladder Cancer • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Genetic Disorders • Glioblastoma • Glioma • Oncology • Pediatrics • Skin Cancer • Solid Tumor

A Phase 2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Patients With DIPG (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: SonALAsense, Inc. | Phase classification: P1/2 ➔ P2

Combination therapy • Phase classification • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

A Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Subjects With Recurrent GBM (clinicaltrials.gov) - P1/2 | N=8 | Active, not recruiting | Sponsor: SonALAsense, Inc. | Recruiting ➔ Active, not recruiting | N=44 ➔ 8

Combination therapy • Enrollment change • Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

SonALAsense Presents Preliminary Data From Clinical Study in Patients With Deadly Pediatric Brain Tumor (Businesswire) - P1/2 | N=27 | NCT05123534 | Sponsor: SonALAsense, Inc. | "SonALAsense...announced the presentation of positive preliminary data from the ongoing Phase 1/2 SDT-201 study in Diffuse Intrinsic Pontine Glioma (DIPG). These results were presented at the November 2023 Society for Neuro-Oncology (SNO) Annual Meeting in Vancouver, Canada. The preliminary data from Study SDT-201 shows signals of clinical activity and no safety concerns....Initial clinical activity observed in the first 5 patients showed partial responses of at least 25% reduction in tumor size in 2 (40%) patients through eight weeks post treatment and stable disease in 2 (40%) patients. Four patients treated have exceeded the median survival of 9-11 months post diagnosis. Patients treated have also maintained or improved their patient performance status."

P1/2 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

FDA Grants Fast Track Designation to SonALAsense’s SONALA-001 in Combination with the INSIGHTEC Transcranial Ultrasound Device for Sonodynamic Therapy of DIPG, a Rare Pediatric Brain Cancer (Businesswire) - "SonALAsense...announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of SONALA-001 in combination with the INSIGHTEC Exablate 4000 Type-2 Device for the treatment of patients with diffuse intrinsic pontine glioma (DIPG)."

Fast track designation • Diffuse Intrinsic Pontine Glioma

Interim report of a phase 1/2 study of sonodynamic therapy (SDT) using aminolevulinic acid (ALA) and low-intensity focused ultrasound in pediatric patients with diffuse intrinsic pontine glioma (DIPG) (SNO 2023) - "SDT signals an innovative and well-tolerated approach for patients with DIPG in our first study cohort. As expected, the PK for SONALA-001 demonstrate rapid infusion and clearance, whereas for PpIX, the PK are consistent with formation of a metabolite. Clinical trial enrollment is ongoing and dose-escalation cohorts will provide additional PK and safety data."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Phase 1/2, first-in-child study of sonodynamic therapy (SDT) using low intensity focused ultrasound and 5-aminolevulinic acid (ALA) for patients with diffuse intrinsic pontine glioma. (ASCO 2023) - P1/2 | "NeuroOnco 2022;24(&):vii72-vii73. Clinical trial information: NCT05123534."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Genetic Disorders • Glioma • Hematological Disorders • Metabolic Disorders • Oncology • Pediatrics • Solid Tumor

A Phase 1/2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2 in Patients With DIPG (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: SonALAsense, Inc. | Phase classification: P2 ➔ P1/2 | N=18 ➔ 27

Combination therapy • Enrollment change • Phase classification • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

A Phase 1/2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2 in Patients With DIPG (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: SonALAsense, Inc. | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2024 ➔ Aug 2024

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2 in Recurrent GBM (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: SonALAsense, Inc. | Trial completion date: May 2026 ➔ Nov 2026

Combination therapy • Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A first-in-human phase 0/1 trial of 5-Aminolevulinic Acid Sonodynamic Therapy (5-ALA SDT) in recurrent glioblastoma (SNO 2022) - " Six hours prior to SDT, adult patients with rGBM were administered 10mg/kg of an IV formulation of 5-ALA (SONALA-001)... This first-in-human Phase 0/1 study of a new therapeutic modality for rGBM patients demonstrates that 5-ALA SDT is safe at 200 to 800J and likely induces targeted cell death in rGBM patients via oxidative stress. At 10mg/kg of 5-ALA, the OBD is at or lower than 200J."

P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3

Study of Sonodynamic Therapy in Participants With Recurrent High-Grade Glioma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Mar 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CASP3

SonALAsense Announces Completion of First Cohort in Phase 2 Study of SONALA-001 Sonodynamic Therapy for Recurrent Glioblastoma (Businesswire) - "SonALAsense...today announced that the first cohort in SDT-202 was fully enrolled. SDT-202 is an open-label, dose-escalation trial of SDT in recurrent glioblastoma (rGBM)....The first cohort in SDT-202 was enrolled at Cleveland Clinic by principal investigator Matthew Grabowski, MD."

Enrollment status • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor