Pipeline

STAR-001

STAR-001 is highly potent and brain permeable small molecule, with properties of synthetic lethality that targets both adult and pediatric CNS tumors. STAR-001 is a prodrug belonging to the class of acylfulvene alkylating antineoplastic agents. It share two key characteristics with acylfulvene: they need to be activated by the enzyme prostaglandin reductase 1 (PTGR1) to become effective against tumors, and they contain a cyclopropyl group in their chemical structure. After being activated, this group can can covalently modify cellular DNA.
Tumors overexpressing PTGR1 or lacking DNA damage repair (DDR) capabilities are especially responsive to its effects. Intracellular PTGR1 converts STAR-001 into a cytotoxic drug that exploits its ability to damage DNA and stall DNA repair mechanisms. Exploiting this mechanism, we have shown STAR-001’s nanomolar potent across many in vitro and in vivo CNS cancer models. STAR-001 hijacks DNA damage repair pathways to selectively exploit vulnerabilities in DDR of tumor cells, triggering cell death in cancerous tissues while sparing healthy cells. Glioblastomas have consistently high levels of PTGR1 expression relative to normal brain tissue, thus increasing the susceptibility to STAR-001.

A) STAR-001 BLOOD BRAIN BARRIER PERMEABILITY

B) STAR-001 BRAIN TUMOR BIOAVAILABILITY

A) STAR-001 BLOOD BRAIN BARRIER PERMEABILITY

B) STAR-001 BRAIN TUMOR BIOAVAILABILITY

*temozolomide

Portfolio

  • Orphan Drug Designation *
  • Rare Pediatric Disease Designation **
  • Multiple GBM patients have been enrolled in the ongoing phase 1a being conducted by Lantern Pharma ***
  • The MTD from the ongoing Phase 1A LP-184 clinical trial is expected to support the later expansion to brain metastases ****

Adult CNS Cancers

STAR-001 exhibits nanomolar potency in intracranial cell-derived xenograft (CDX) models of glioblastoma (GBM), where several rounds of treatment with STAR-001 induced significant tumor regression at nanomolar levels. Brain permeability assays (brain tissue/blood plasma) comparing STAR-001 vs standard of care, temozolomide (TMZ), in GBM CDX mouse models, demonstrated that STAR-001, similar to TMZ, penetrates the brain tumor itself at twice the rate of the peritumoral normal brain.
Moreover, whereas TMZ elicits therapeutic effects primarily in GBM with MGMT promoter methylation, seen in ~35% of all newly diagnosed GBM, MGMT-deficient GBM, seen in 65% of all newly diagnosed GBM, is resistant to TMZ. By contrast, STAR-001 treatment reduces tumor volume compared to control, irrespective of the GBM methylation status in CDX models, indicating that STAR-001 compares favorably to the current standard of care (SOC). Consequently, STAR-001 may qualify for a Fast Track designation since there is no current SOC for newly diagnosed GBM, that has an unmethylated MGMT promoter. We believe that STAR-001 treatment could result in a major improvement to GBM treatments. Starlight plans on filing for a Fast Track designation in TMZ-resistant GBM.
MGMT Negative
MGMT Positive
11310
Mayo39- TMZR
LN18

STAR-001 has Nanomolar Potency in Brain Metastases Cell Lines

Pediatric CNS Cancers

One of Starlight’s corporate goals is to bring new precision-based therapies for CNS childhood cancers, and as the first step, Starlight has developed STAR-001 as potential treatment for ATRT, an ultra-rare childhood brain cancer. Lantern’s RADR® platform predicted in silico efficacy of STAR-001 in ATRT which was later validated using preclinically models. In vitro testing on SMARCB1-deficient ATRT cell lines demonstrated STAR-001's potent efficacy, surpassing the FDA approved agent carmustine. In vivo experiments on mice implanted with cell line -derived xenografts showed near-complete tumor regression with STAR-001 treatment, underscoring its potential as a therapy for ATRT. This data has been documented in peer review publications and scientific posters. While we have a delineated path for expedited regulatory approval in ATRT, given the recent rare pediatric disease designation by the FDA, our plan is to initiate a Phase 1a clinical trial for various pediatric CNS tumors, as soon as safety and optimal dosing has been achieved in adults.