Cohort 1 of multiple‑dose REYOBIQ in LM shows no dose‑limiting toxicities; safety signal but financing and efficacy unknowns remain

What happened

Plus Therapeutics presented three REYOBIQ clinical data posters at the 2025 WFNOS/SNO meeting, and Cohort 1 of the multiple‑dose ReSPECT‑Leptomeningeal Metastases (LM) trial reported no dose‑limiting toxicities. This early multiple‑dose safety signal complements prior single‑dose LM findings that showed reductions in CSF tumor cell counts and supports continued dose‑optimization toward a potential registrational path. Absence of DLTs in a small cohort is a helpful but limited safety result — it is not evidence of efficacy, durability, or reproducible delivery across centers using CED/Ommaya approaches. The company’s financial and operational fragility remains acute: 9M25 operating cash outflow was $14.5M versus $13.3M cash on hand, Nasdaq minimum bid relief is temporary, and isotope/manufacturing logistics and CED execution still pose material program risk. In short, the data modestly reduce the binary safety risk and keep the LM Fast Track story alive, but investors should wait for larger safety/efficacy cohorts, formal FDA alignment, or fresh non‑dilutive financing before changing exposure materially.

Implication

The lack of dose‑limiting toxicities in Cohort 1 meaningfully reduces one immediate downside (catastrophic toxicity) and permits continued dose‑escalation and enrollment, which is positive for the LM Fast Track narrative. However, the cohort is small and short follow‑up; absence of DLTs does not equate to clinical benefit, so efficacy readouts remain the decisive next step. Key catalysts to watch are dose‑optimization results, any formal FDA agreement on a registrational path, and broader safety/efficacy data from larger cohorts. Equally important are financing events and grant receipts (CPRIT/NIH/DoD) and progress on Nasdaq compliance — failure to secure capital would likely force dilution or program delays. For investors that remain interested, treat PSTV as a small, event‑driven exposure and demand either robust efficacy data or clear non‑dilutive financing before increasing position size.

Thesis delta

The new Cohort 1 multiple‑dose no‑DLT result slightly improves the safety profile for REYOBIQ in LM and modestly raises the probability of a viable dose‑optimization pathway toward registrational discussions. It does not change the core DeepValue view: valuation and conviction remain constrained by limited cash runway, Nasdaq compliance risk, isotope/manufacturing execution challenges, and the absence of confirmatory efficacy data.