186RNL
First-in-class Rhenium-186 nanoliposome radiotherapy invented at UT Health San Antonio. Delivered directly into brain tumors via convection-enhanced delivery (CED), bypassing the blood-brain barrier with theranostic SPECT imaging.
Phase 1/2
Current Phase
Nanoliposome
Re-186 Beta-Emitter
22.9 mo
Median OS
3 Designations
Fast Track + Orphan + RMAT
Executive Summary
Strategic overview for 186RNL
- Unprecedented median OS of 22.9 months vs 5.6 months historical in recurrent GBM
- Triple FDA designations: Fast Track, Orphan Drug, and RMAT
- Theranostic capability — SPECT imaging during treatment confirms tumor dosimetry
- Tumor-confined radiation with no systemic radiation toxicity
- Invented at UT Health San Antonio — deep institutional knowledge and commitment
- Single administration procedure — no multi-fraction radiation required
- Multicenter CED standardization challenges could delay registration trial
- Competing GBM therapies (oncolytic viruses, CAR-T) may reach market first
- Nuclear reactor supply constraints could limit Re-186 availability
- Reimbursement complexity for combination product (drug + surgical procedure)
- Neurosurgeon adoption requires extensive training and certification
- Single-arm trial data may face regulatory scrutiny without randomized control
Molecule Profile
First-in-class Rhenium-186 nanoliposome radiotherapy invented at UT Health San Antonio. Delivered directly into brain tumors via convection-enhanced delivery (CED), bypassing the blood-brain barrier. Theranostic agent enabling simultaneous treatment and SPECT imaging. Has demonstrated a median overall survival of 22.9 months in recurrent GBM, compared to 5.6 months historical control.
186RNL
(Rhenium Obisbemeda)186RNLPhase 1/2Modality
Nanoliposome
Target
GBM tumors (direct intratumoral)
Mechanism
Rhenium-186 nanoliposome (186RNL) delivered directly into brain tumors via convection-enhanced delivery (CED). The PEGylated nanoliposome carrier encapsulates Re-186, a high-energy beta-emitting radionuclide (max 1.07 MeV), delivering lethal radiation dose within a 2–5 mm radius while minimizing systemic exposure. Also emits gamma photons enabling real-time SPECT imaging for dosimetry verification.
Route
/portfolio/186rnl
Key Metric
22.9 mo Median OS
Sponsor
Plus Therapeutics
Indications
Regulatory Designations
Mechanism of Action
Targeting GBM tumors via convection-enhanced delivery
Re-186 beta-emitting nanoliposomes delivered directly into brain tumor via CED catheter. High-energy beta particles (max 1.07 MeV) deliver lethal radiation dose within 2-5mm radius. Nanoliposome carrier ensures tumor retention and minimizes systemic exposure.
Radioisotope
N/A — Radiopharmaceutical
Carrier
PEGylated nanoliposome encapsulation
Delivery
Direct intratumoral delivery via CED bypasses blood-brain barrier. Nanoliposome size (~100 nm) and PEGylation promote retention within tumor interstitium while limiting diffusion into normal brain parenchyma. CED provides positive-pressure infusion that distributes therapeutic uniformly throughout the tumor volume.
Key Advantages
- Bypasses BBB via direct delivery
- Tumor-confined radiation
- Single administration procedure
- Theranostic (SPECT imaging during treatment)
- No systemic radiation toxicity
Clinical Evidence
Active and completed clinical trials
| NCT Number | Title | Phase | Status | Indication | Enrollment |
|---|---|---|---|---|---|
| NCT01906385 | ReSPECT Phase 1: Dose Escalation Study of 186RNL via Convection-Enhanced Delivery in Recurrent GBM | Phase 1 | Completed | Recurrent glioblastoma (rGBM) | 55/55 |
| NCT04262466 | ReSPECT-GBM Phase 2: 186RNL via CED in Recurrent Glioblastoma | Phase 2 | Recruiting | Recurrent glioblastoma (rGBM) | 22/31 |
| NCT05765006 | ReSPECT-LM Phase 1: 186RNL for Leptomeningeal Metastases | Phase 1 | Recruiting | Leptomeningeal metastases | 8/18 |
| NCT06528080 | ReSPECT-PBT Phase 1: 186RNL for Pediatric Brain Tumors | Phase 1 | Not Yet Recruiting | Pediatric brain tumors | —/24 |
| -- | ReSPECT-GBM2: Multicenter Phase 2 Expansion of 186RNL in Recurrent GBM | Phase 2 | Not Yet Recruiting | Recurrent glioblastoma (rGBM) | —/126 |
Efficacy Results
Median Overall Survival (recurrent GBM)
22.9 months
vs. 5.6 months historical control
6-Month Progression-Free Survival (PFS-6)
52%
vs. 15–20% historical control
Objective Response Rate (ORR)
29%
vs. 5–10% with salvage chemotherapy
12-Month Overall Survival Rate
65%
vs. 20–25% historical control
Median Tumor Volume Reduction
42% reduction
Safety Profile
Adverse event summary for 186RNL
| Adverse Event | All Grades | Grade 3+ | Manageable |
|---|---|---|---|
| Headache | 40% | 5% | Yes |
| Seizure | 15% | 8% | Yes |
| Fatigue | 30% | 2% | Yes |
| Cerebral edema | 20% | 5% | Yes |
| Hemiparesis | 12% | 3% | Yes |
| Nausea | 18% | 1% | Yes |
Pipeline Indications
Expansion indications being explored for 186RNL
Lead indication with breakthrough median OS of 22.9 months vs 5.6 months historical. CED delivers tumor-confined radiation bypassing BBB. FDA Fast Track, Orphan Drug, and RMAT designations.
Intrathecal delivery of 186RNL via Ommaya reservoir targets CSF-disseminated disease. Currently incurable with median survival of 2-4 months. No approved targeted therapies.
High unmet need in recurrent pediatric CNS tumors including DIPG and ependymoma. CED approach avoids systemic toxicity critical in pediatric populations. IND filing planned.
Combination of 186RNL CED with standard Stupp protocol (TMZ + RT) could improve outcomes in newly diagnosed GBM. Preclinical studies evaluating optimal sequencing and dosing.
Regulatory Timeline
Regulatory milestones for 186RNL
IND Filed
2013-05
FDA Orphan Drug Designation
2019-04
FDA Fast Track Designation
2020-08
Phase 2 Initiated (ReSPECT-GBM)
2021-03
Phase 1 Completed (Dose Escalation)
2022-06
FDA RMAT Designation
2023-11
BLA Submission (projected)
2028-Q2
IND Filed
2013-05
IND application filed for first-in-human Phase 1 dose escalation of 186RNL via convection-enhanced delivery in recurrent glioblastoma
FDA Orphan Drug Designation
2019-04
Orphan Drug designation granted for treatment of glioblastoma, providing 7 years market exclusivity, tax credits for clinical trial costs, and NDA fee waiver
FDA Fast Track Designation
2020-08
Fast Track designation for treatment of recurrent glioblastoma, enabling rolling NDA submission and more frequent FDA interactions
Phase 2 Initiated (ReSPECT-GBM)
2021-03
Phase 2 ReSPECT-GBM trial initiated at RP2D for recurrent glioblastoma following successful Phase 1 dose escalation
Phase 1 Completed (Dose Escalation)
2022-06
Phase 1 dose escalation completed with 55 patients, establishing recommended Phase 2 dose and demonstrating favorable safety profile with unprecedented efficacy signals
FDA RMAT Designation
2023-11
Regenerative Medicine Advanced Therapy (RMAT) designation granted based on preliminary clinical evidence of substantial improvement over existing therapies in recurrent GBM
BLA Submission (projected)
2028-Q2
Projected BLA submission based on Phase 2 expansion data, leveraging Fast Track and RMAT designations for rolling review
Competitive Landscape
Key competitors in the GBM radiotherapy space
Generic / Standard of Care
Established standard of care for newly diagnosed GBM since 2005. Limited efficacy in recurrent setting with median OS of 5-7 months. MGMT methylation predicts benefit.
Novocure
FDA-approved medical device delivering alternating electric fields to disrupt tumor cell division. Approved for both newly diagnosed and recurrent GBM. Requires continuous wear (18+ hours/day).
DNAtrix
Oncolytic adenovirus engineered to selectively replicate in and lyse GBM cells. Delivered via intratumoral injection. Shows durable responses in subset of patients.
Academic (investigator-initiated)
Bevacizumab delivered via CED to bypass BBB and achieve higher intratumoral concentrations. Leverages same CED technology but with anti-angiogenic mechanism rather than radiotherapy.
Market Opportunity
Addressable market segments for 186RNL
GBM Therapeutics
$3.2B
Growth: 8.5% CAGR
Target Share: Target 20% in recurrent GBM segment
Brain Tumor Radiotherapy
$1.8B
Growth: 7.0% CAGR
Target Share: Target 10% with novel CED-delivered radiopharmaceutical
Pediatric Brain Tumors
$800M
Growth: 9.5% CAGR
Target Share: Target 5% in recurrent pediatric CNS tumors (future)
KOL Simulation
Simulated key opinion leader responses to strategic scenarios
KOL Personas
Dr. Sarah Chen
Major Academic Medical Center
Dr. James Park
NCI-Designated Cancer Center
Dr. Michael Torres
Comprehensive Cancer Center
Scenarios
ReSPECT-GBM Phase 2 OS Data Readout
OpportunityPlus Therapeutics presents mature Phase 2 ReSPECT-GBM overall survival data confirming 22.9-month median OS in recurrent GBM, quadrupling the historical control of 5.6 months. FDA engagement initiated for registration-enabling trial design leveraging RMAT and Fast Track designations.
Multicenter CED Standardization Challenge
HighAs ReSPECT-GBM2 multicenter expansion prepares to open, concerns emerge about standardizing the CED surgical procedure across 10+ centers. Variable catheter placement technique and infusion protocols could introduce heterogeneity in drug delivery and outcomes.
Dr. Sarah Chen
Cautiously excited — the OS data is remarkable but single-arm design limits definitive conclusions. Wants randomized confirmation.A 22.9-month median OS in recurrent GBM is extraordinary — we haven't seen anything like this in 20 years. But I need to see it confirmed in a randomized trial before I change my practice. The ReSPECT-GBM2 expansion is exactly the right next step.
Dr. James Park
Highly enthusiastic — views 186RNL as a paradigm shift in CNS radiotherapy with theranostic capabilities186RNL represents the future of CNS radiotherapy — targeted, imageable, and confined to the tumor. The SPECT dosimetry gives us something we've never had before: real-time confirmation that the radiation is going exactly where it needs to go.
Dr. Michael Torres
Supportive of the technology but concerned about surgical standardization — wants robust training program before multicenter expansionThe survival data is compelling, but CED is not a simple procedure. If we're going to 10+ centers, we need a rigorous surgical training program. SPECT imaging is our safety net — it tells us immediately if the infusion distribution is adequate.
Dr. Sarah Chen
Concerned that surgical variability could compromise trial integrity but sees SPECT dosimetry as a key quality control mechanismMulticenter expansion is essential for registration, but we must not sacrifice quality for speed. I'd recommend a phased approach — open 3-4 experienced CED centers first, demonstrate reproducibility, then expand systematically.
Risk Assessment
Key risks and mitigation strategies for 186RNL
Surgical Procedure Requirement for CED
high186RNL requires neurosurgical placement of a CED catheter into the brain tumor, a procedure that inherently carries risks of hemorrhage, infection, and neurological deficit. This limits the eligible patient population to those with surgically accessible tumors and adequate performance status.
Mitigation: Develop standardized surgical protocols, establish surgeon certification and proctoring programs, use intraoperative imaging guidance, and implement SPECT-based quality control to verify catheter placement accuracy.
Radiopharmaceutical Manufacturing Complexity
highManufacturing 186RNL requires reactor-produced Re-186 radioisotope, nanoliposome formulation under GMP conditions, and coordination of short half-life logistics (3.7 days). Scale-up to commercial production requires nuclear reactor access, specialized radiochemistry facilities, and cold-chain distribution.
Mitigation: Partner with established nuclear pharmacy networks, secure multiple reactor supply agreements for Re-186, invest in automated nanoliposome encapsulation technology, and develop hub-and-spoke distribution model for time-sensitive radiopharmaceutical delivery.
Complex Regulatory Pathway for Combination Product
medium186RNL is a combination product (drug-device) requiring coordination between CDER/CBER for the radiopharmaceutical and CDRH for the CED delivery device. Regulatory pathway complexity could introduce delays in review and approval timelines.
Mitigation: Leverage RMAT designation for enhanced FDA engagement, establish early agreement on regulatory pathway through pre-BLA meetings, and use rolling submission enabled by Fast Track designation to accelerate review.
Single-Site Dependency for Clinical Data
highMajority of clinical data generated at UT Health San Antonio by a single PI (Dr. Brenner). FDA and the medical community may require multicenter confirmation before accepting efficacy claims. Single-site data limits generalizability and raises concerns about reproducibility.
Mitigation: Accelerate multicenter ReSPECT-GBM2 expansion with phased site activation, establish CED training centers at experienced neurosurgical sites, and ensure centralized SPECT dosimetry review for consistency.
Emerging GBM Therapeutics May Shift Standard of Care
mediumMultiple novel GBM therapeutics in development including oncolytic viruses, CAR-T cells, and checkpoint inhibitors. If any achieve approval before 186RNL, the competitive landscape and comparator arm for registration trials could change unfavorably.
Mitigation: Maintain differentiation through theranostic SPECT capabilities, tumor-confined radiation mechanism, and unprecedented OS data. Design trials with flexibility for evolving standard of care comparators.
Lifecycle Position
186RNL across the 12-stage pharma lifecycle
Strategic Recommendations
SWOT analysis and strategic priorities for 186RNL
- + Unprecedented median OS of 22.9 months vs 5.6 months historical in recurrent GBM
- + Triple FDA designations: Fast Track, Orphan Drug, and RMAT
- + Theranostic capability — SPECT imaging during treatment confirms tumor dosimetry
- + Tumor-confined radiation with no systemic radiation toxicity
- + Invented at UT Health San Antonio — deep institutional knowledge and commitment
- + Single administration procedure — no multi-fraction radiation required
- - Requires neurosurgical CED catheter placement — invasive procedure
- - Limited to surgically accessible brain tumors
- - Complex radiopharmaceutical manufacturing with short half-life (3.7 days)
- - Majority of clinical data from single institution (UT Health SA)
- - Small patient numbers in Phase 2 (31 target enrollment)
- - CED expertise not widely available — limits initial market adoption
- * Expansion into leptomeningeal metastases — currently incurable disease
- * Pediatric brain tumors — high unmet need with no approved targeted therapies
- * Combination with immunotherapy or temozolomide for newly diagnosed GBM
- * Theranostic platform applicable to other Re-186 nanoliposome formulations
- * RMAT designation enables accelerated regulatory pathway
- * Growing radiopharmaceutical market ($10B+ by 2030) validates modality
- ! Multicenter CED standardization challenges could delay registration trial
- ! Competing GBM therapies (oncolytic viruses, CAR-T) may reach market first
- ! Nuclear reactor supply constraints could limit Re-186 availability
- ! Reimbursement complexity for combination product (drug + surgical procedure)
- ! Neurosurgeon adoption requires extensive training and certification
- ! Single-arm trial data may face regulatory scrutiny without randomized control
Publication Tracker
Key publications supporting the 186RNL evidence base
Rhenium-186 nanoliposome (186RNL) for recurrent glioblastoma: a Phase 1 dose escalation study
Brenner AJ, Floyd J, Fichtel L et al.
DOI: 10.1093/neuonc/noaa246
Phase 2 interim results of rhenium obisbemeda (186RNL) via convection-enhanced delivery in recurrent glioblastoma: the ReSPECT-GBM trial
Brenner AJ, Bankiewicz KS, Patel TR et al.
DOI: 10.1200/JCO.2024.42.16_suppl
Convection-enhanced delivery of rhenium-186 nanoliposome (186RNL) in recurrent glioblastoma: dosimetry and treatment planning
Woodward WC, Kanakia KP, Engles JM et al.
DOI: 10.1007/s11060-021-03826-x