Phase 1 data in 78 healthy volunteers showed CG001419 was well tolerated across single- and multiple-ascending doses with no drug-related serious adverse events. The randomized, placebo-controlled, double-blind study (NCT06636500) also assessed food effect and pharmacokinetics at a single Australian site.
Cullgen has completed first-in-human testing of CG001419, an oral pan-TRK degrader being advanced as a non-opioid analgesic, and plans to file an IND in early 2026 to begin a U.S. Phase 2 study in acute post-operative pain using the bunionectomy model. In parallel, the company is testing the same molecule in a separate Phase 1 study in China in patients with solid tumors. Beyond its lead, Cullgen is progressing CG009301, a GSPT1 degrader in Phase 1 for hematologic malignancies, and says additional degrader and degrader–antibody conjugate programs are moving into IND-enabling work, including candidates in cell cycle targets and inflammatory diseases.
Strategically, this is an expansion play that pushes targeted protein degradation beyond oncology and into pain, a category hungry for credible non-opioid options yet littered with mechanisms that have stumbled on efficacy or safety. Targeting the TRK axis taps directly into NGF-mediated pain signaling, but does so via degradation rather than inhibition—a mechanistic nuance that could matter for both durability and adverse event profiles. Running the FIH study under Australia’s ethics pathway speeds early signal generation and cost control, while teeing up a U.S. IND for the more commercially relevant bunionectomy readout. The dual use of CG001419 in oncology provides a separate safety and exposure dataset that may help frame dose selection, even if the therapeutic indexes for cancer and pain diverge.
For sites and CROs, a bunionectomy trial offers a familiar, operationally contained model with clean endpoints such as SPID and opioid rescue use. The completed food-effect work should simplify Phase 2 dosing logistics and pharmacy workflows. However, Phase 2 execution will hinge on tight surgical scheduling, standardized anesthesia protocols, and rigorous rescue medication management to maintain assay sensitivity—areas where many non-opioid analgesics have failed to differentiate. Regulators will look for clinically meaningful opioid-sparing and functional outcomes, not just nominal pain score deltas, and may press for broader chronic pain plans if the acute signal is positive. Given the on-target biology, vigilance for sensory and proprioceptive adverse events will be critical; even if no serious events emerged in healthy volunteers, real-world post-op populations may surface hyposensitivity or dysesthesia signals at effective exposures.
Vendors and assay partners should note the need for credible pharmacodynamic readouts of TRK pathway modulation to bridge from healthy volunteer PK to analgesic effect. If Cullgen can demonstrate target engagement that correlates with pain outcomes, it strengthens both regulatory arguments and payer narratives in a crowded non-opioid field that spans Nav1.7, NGF, and TRP mechanisms. Manufacturing and CMC readiness for chronic or repeat dosing of a degrader will also draw scrutiny, as will drug–drug interaction risk in perioperative settings.
Next, watch for IND timing, Phase 2 dose levels relative to Phase 1 exposure margins, and whether the protocol is powered for opioid-sparing claims alongside pain reduction. Any early signs of sensory adverse events or imbalance in rescue medication will be telling for the class. On the corporate side, clarity on financing and partnerships to support a U.S. pain program—and a parallel oncology path—will indicate how aggressively Cullgen plans to scale the degrader modality beyond its oncology roots.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
