The Challenge of GBM
Glioblastoma remains one of oncology’s most lethal and treatment-resistant tumors. Persistent resistance and poor outcomes underscore the need for new mechanisms in GBM.
Existing standard therapies are associated with significant side effects and treatment burden, and overall outcomes remain poor. There remains a critical unmet medical need for therapies that achieve potent, localized activity without increasing systemic burden.
How PoMA Works
Alpheus is developing Porphyrin Metabolite Activation (PoMA™), a drug-led, tumor-selective oncology approach designed to activate 5-ALA–derived protoporphyrin IX (PpIX), beginning with glioblastoma. Clinical studies utilizing this approach have previously been described in the literature under the broader category of sonodynamic therapy (SDT).
Patients receive 5-aminolevulinic acid (5-ALA), an oral small molecule that enters the heme biosynthesis pathway and is metabolized to protoporphyrin IX (PpIX). 5-ALA is approved for intraoperative visualization of malignant glioma based on preferential PpIX accumulation in tumor tissue. 5-ALA–derived PpIX accumulates preferentially in malignant glioma tissue, creating a substrate for localized activation.
After the drug has accumulated, the Alpheus LIDU™ system delivers low-intensity defocused ultrasound across the affected brain hemisphere. PoMA uses a controlled, non-thermal ultrasound stimulus to activate tumor-resident PpIX. Activation of intratumoral PpIX generates reactive oxygen species (ROS), contributing to localized tumor cell injury. Early research suggests PoMA-induced tumor cell damage may also engage immune-related mechanisms and support immune visibility.
The goal of PoMA is to achieve localized pharmacologic activity in tumor tissue while limiting systemic exposure. Safety and effectiveness are currently being evaluated in clinical trials.
Evidence From our Studies
The Alpheus program is built on stepwise translation from spontaneous canine GBM to human studies and an ongoing randomized Phase 2b trial. Findings remain preliminary and investigational, and cross-study comparisons should be avoided. Each study was designed to establish feasibility, characterize safety, and explore biological and clinical signals consistent with localized drug activation. Findings remain preliminary and investigational, and cross-study comparisons should be avoided.
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status
Spontaneous Canine GBM
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status: Completed
Naturally occurring high-grade gliomas in companion dogs closely mirror human GBM biologically and genomically. In spontaneous canine GBM, PoMA produced localized apoptotic tumor cell death and was well tolerated with repeat monthly treatment, with no evidence of injury to normal brain. These biological effects were accompanied by an observed prolongation of survival versus center-matched controls. Results are from an animal study and may not predict human outcomes.1.
Recurrent GBM
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status: Completed
In recurrent GBM, repeat monthly PoMA treatments were safe and generally well tolerated in a small cohort, with preliminary imaging and survival trends consistent with localized drug activation.2 These findings require confirmation in larger, controlled studies.
Newly Diagnosed GBM
Single Treatment
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status: Completed
A single neoadjuvant PoMA treatment in newly diagnosed GBM was designed to evaluate biological activity rather than clinical efficacy. The study showed evidence of localized tumor effect, including cytotoxic edema on MRI within 24 hours and histologic evidence of apoptosis by cleaved caspase-3 (CC3) staining. These findings support the biological activity of PoMA in human GBM; clinical benefit has not been established.3
Newly Diagnosed GBM
Safety Lead-In
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status: Enrollment Complete (Follow-up Ongoing)
The Phase 1b safety lead-in evaluated PoMA in newly diagnosed glioblastoma. Across these small cohorts, treatment was feasible and generally well tolerated, with no dose-limiting toxicities observed. Exploratory biological signals were observed, but findings remain preliminary and derived from small sample sizes; efficacy conclusions cannot be drawn.
Newly Diagnosed GBM
RCT
Preclinical
Phase 1
Phase 1b
Phase 2
Phase 2b
Status: Active / Enrolling
A randomized, double-blind, placebo-controlled Phase 2b trial in newly diagnosed glioblastoma is actively enrolling. The study is evaluating PoMA as an adjunct to standard chemoradiation under an IRB-approved protocol.
PoMA Differentiation
PoMA is distinguished by its drug-centered approach and a non-invasive, low-intensity defocused ultrasound field designed to activate tumor-resident PpIX across the affected region, consistent with the infiltrative nature of glioblastoma. This design aims to support broad, localized drug activation across the tumor region—a different approach from focused ultrasound technologies developed for discrete, focal targets.
Together, the selective accumulation of the drug and the system’s coverage geometry represent a therapeutic concept designed to be both localized and repeatable. The potential clinical benefit of this approach is currently being evaluated in ongoing studies.
PoMA Platform
Potential
While Alpheus’ lead program is focused on glioblastoma, PoMA is designed around tumor-localized porphyrin metabolite biology and localized activation. The potential applicability of this approach beyond GBM remains early-stage and investigational.
References: 1. Arnold SA, Taylor AR, Hansen K, Agarwal V, Low WC, Pluhar GE. Immunotherapy yields breed-specific worst survival outcomes among three investigated therapies in French bulldogs with high-grade glioma. Front Vet Sci. 2025 Mar 19. 2. Alpheus, 2023: Phase 1/2 results in recurrent GBM 3. Alpheus, 2024: Early clinical results in newly diagnosed GBM.