Surgery-free, drug-free deep-brain neuromodulation for pain and depression — if Phase 3 confirms Phase 2.
Spire Therapeutics
venture active confidence: Medium status: Draft updated 2026-07-14
Summary
Spire Therapeutics is developing Diadem, focused ultrasound meant to modulate deep brain circuits involved in chronic pain and depression. If Phase 3 succeeds and FDA clears it, Diadem could offer a rapid, noninvasive alternative where drugs and shallower stimulation fall short.
Impact
Roughly one in three patients with chronic pain or major depression do not respond adequately to first-line treatments (opioids, antidepressants). Deep brain stimulation works for some but is invasive, costly, and risky. SPIRE cites ~20M Americans with treatment-resistant chronic pain and ~6M with treatment-resistant depression.
A cleared office-based device that rapidly reduces pain and depressive symptoms without surgery or chronic medication could reshape treatment algorithms for two of the largest healthcare cost categories globally. The company frames impact broadly — including links to addiction, homelessness, and incarceration — because untreated pain and depression drive downstream social costs.
What They Are Building
Diadem delivers precise low-intensity ultrasonic pulses through the skull to reset overactive deep brain regions. The core technical challenge is transcranial ultrasound through variable skull acoustic properties: bone refracts and attenuates energy, and hair adds further distortion. Diadem's correction method — published in Nature Communications Engineering — uses imaging-derived patient-specific models to deliver controlled, effective doses to specified deep targets.
Clinical programs listed publicly include treatment-resistant chronic pain (~23 participants, results pending publication), treatment-resistant depression (20-participant follow-up trial, results pending), and essential tremor neuromodulation (initial results in Journal of Neural Engineering). A stated forward challenge is eliminating MRI-based guidance to broaden access.
The mechanism of LIFU neuromodulation — exactly how ultrasound modulates neural circuits — remains incompletely understood, which may affect FDA labeling and physician adoption framing.
What They Need Now
Likely needs include biomedical engineers (acoustics, ultrasound, neuroimaging), clinical-research operations for Phase 3 execution, regulatory affairs and FDA strategy specialists for novel neuromodulation devices, reimbursement and market-access operators, and manufacturing partners for device scale-up. No disclosed Series A; clinical trial costs may require significant new capital beyond grant and competition wins.
Who Could Help
Useful helpers include Focused Ultrasound Foundation connectors, pain and psychiatry clinical KOLs, neuroimaging scientists for guidance simplification, FDA regulatory consultants with neuromodulation precedents, hospital neurology and pain-clinic champions, and strategic device partners. SPIRE states openness to partnerships that accelerate patient access.
Utah Context
SPIRE is a University of Utah Biomedical Engineering spinout headquartered in Salt Lake City, with University of Utah Health listed as a funder. It sits in Utah's neural-engineering and medtech cluster alongside Epitel, Blackrock Neurotech, and the broader U of U technology-transfer pipeline. Altitude Lab residency places it in the state's life-science incubator ecosystem.
Evidence
See Also
- Epitel — Utah neighbor in non-invasive neural monitoring (scalp EEG versus transcranial ultrasound)
- Blackrock Neurotech — contrasting Utah neural-interface lineage (implantable BCI versus non-invasive LIFU)
Open Questions
- Phase 3 design, endpoints, and timeline are not fully public; outcome remains the tier-moving event.
- FDA regulatory pathway for novel LIFU neuromodulation has limited precedent — labeling claims may hinge on mechanism understanding.
- Can Diadem eliminate MRI guidance while maintaining targeting precision and safety?
- Comparative effectiveness versus TMS, ECT, and ketamine protocols for treatment-resistant depression is not established on this page.
- Funding runway and capital strategy beyond grants and pitch prizes are not publicly disclosed.
- No agent-readable careers/jobs page found (spire.us/careers 404).