The following quotation is the "detailed description" of the visceral mets CRPC trial sponsored by Edwin Posadas of Cedar-Sinai. Though I realize the importance of the Comet trials as the necessary statsig pathway to regulatory acceptance, these smaller peripheral trials powered to witness the biology and lend clarity to the MOA of Cabo are vastly more interesting to me. Biomarker recognition, biopsies, and gainful use of RUO investigational assay devices constitute the cutting edge of Cabo research, and I think that we are due a surprise from any one of these CRADA/CTEP - IST-type confirmation trials. A surprise that could literally come at any time. Confirmation of positive biological response to Cabo therapy could easily have a significant impact on SP...and possibly bode well for fast-tracking to a priority review. A perceived "miracle" of healing of the bone micro environment could substantially alter the EXEL market cap overnight...and perhaps even qualify Cabo for breakthrough designation.
" (XL184), a multi-targeted tyrosine kinase inhibitor, has demonstrated a powerful clinical phenotype in men with metastatic castrate resistant prostate cancer (mCRPC) both before and after chemotherapy. This phenotype consists of rapid reduction in pain (when present) and improvement in bone scans that may or may not be accompanied by decrease in serum prostate specific antigen (PSA) concentrations. In previous studies of cabozantinib in advanced prostate cancer, patients with visceral disease have been excluded. Hence, this protocol creates a unique opportunity to define the activity of this disease in the population of men with visceral
disease - a marker for poorer prognosis in mCRPC."
Wilder your statement "A surprise that could literally come at any time" is what makes this drug and investment so different than many of the "winners" listed as having outperformed EXEL over the past 2 years. Yes, the Comet trials are huge and if successful will undoubtedly propel this companys valuation to multiple billions. But there are 40+ clinical trials, covering an extrordinarily large number of possibilities for this unique compound. So a moderate success here would be with late line patients in mCRPC. Combine that with MTC and let's say a 30-50% share of the MM market with Roche /GDC 0973, and investors will undoubtedly do quite well. But the possibility of blockbuster success...so many different places this drug could plug in...pain palliation, bone mets healing, CRPC, HCC, RCC, MTC, combination/targeted therapies, etc. The odds are better for some, less so for others, but the facts are that EXEL, IST's and CRADA are all investing millions in clinical trials predicated on the "mysterious" and "unprecedented" MOA of this compound. How many "winners" in these indications will it take to see a 10B valuation? Is it even possible?
Great post Wilder.
Very interesting phase II trial on mCRPC patients with visceral mets!
COMET-1 excludes Liver or brain metastases or cranial epidural disease. And this new phase 2 trial basically covers mCRPC patients with visceral (does not exclude bone) mets.
However, this new trial excludes patients with intestinal mets if risk of perforation present. It is obvious that this trial is mainly targeting liver mets in mCRPC patients. Liver mets is one of the most common sites if not the most comment site.
Cabo has demonstrated efficiency on HCC.
All these make me wonder, if Cabo can also play an important role in patieints with metastatic adenocarcinoma to liver of unknown primary?