Innovation Pharmaceuticals Inc (IPIX)

[biodoc]

Nonsensical arguments. The trial protocol presented an obstacle to enrollment. After evaluation of the few patients enrolled in cohort 1 (apparently without adverse events) the company learned the following:

Modulation of the p53 protein was observed in response to administration of Kevetrin. Pathways analyses also point to concomitant cell cycle modulation at the level of gene expression. Importantly, these data are the first to directly support, in ovarian cancer patient tumors, Kevetrin’s ability to affect p53 and associated molecular pathways—a central gene signaling network involved in regulating cell growth and the cell cycle, helping to prevent cancer.

In more detail, preliminary analyses used Western Blots to assess relative levels of key proteins extracted from tumor biopsies before and after a series of nine Kevetrin infusions administered over three weeks. The level of phospho-p53, the activated form of the protein, in addition to the noted p53 modulation, was also seen to change in response to Kevetrin administration. These findings confirm in patient tumors Kevetrin-induced anti-cancer effects similar to those demonstrated (pdf) preclinically in ovarian cancer cell-lines. These new data reinforce prior clinical data, from the earlier concluded Phase 1 study of Kevetrin in advanced solid tumors (see NCT01664000), in which observations of p21 expression in peripheral blood monocytes supported p53 involvement in Kevetrin’s mechanism of action.

Data from RNAseq analyses of expressed mRNAs and sRNAs in tumors, before and after treatment with Kevetrin, are being further analyzed to assess the nature and scope of molecular pathways modulations. The strongest signal so far detected concerns the cell cycle and a variety of transcription factors.

PR 12/27/2017

Here are the primary outcome measures:

Primary Outcome Measures :
Incidence of Treatment-Emergent Adverse Events [ Time Frame: 6 Weeks ]
Reporting of Adverse Events, and severity of adverse events

Evaluate changes in biomarkers between pre-treatment sample and post-treatment sample [ Time Frame: 3 Weeks ]
Changes in RNA and/or protein level of pre-specified biomarkers associated with the p53 signalling pathway and apoptosis will be compared between pre-treatment sample (tumor biopsy, ascites fluid, and peripheral blood) and post-treatment sample (tumor biopsy, ascites fluid, and peripheral blood)

A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer


So with a slowly enrolling and likely under-dosed trial and successful determination of biomarker changes, what's reasonable? Keep going for a year to try to fully enroll the 2nd cohort or move along with data gleaned from Cohort 1? If there wasn't clear-cut biomarker effect from the cohort 1 then it'd make sense to proceed with cohort 2. In that the Kevetrin dosing is only 9 doses over 3 weeks, it makes little sense to continue the trial as a therapeutic trial. I think it would also be difficult to assess progression of disease with such a short therapeutic time-frame. The trial, as designed, is a tough sell to late stage patients. It makes a lot more sense to create conditions where a therapeutic trial can yield positive results beyond the 3 week dosing window. Biomarker information acquired from cohort 1. Well done. Move on to a therapeutic-focused trial.

Frequent oral dosing is certainly an understandable strategy for a short half life drug. I get it. Personally, and I've expressed this before, I'd like to see escalating dosing with a continuous infusion via a Port-A-Cath or Hickman like access port. User friendly portable devices are available. It's a more expensive and invasive approach but it'd tell us the therapeutic impact and side effects of steady state Kevetrin fairly quickly. Many of these late-stage patients already have indwelling venous access ports.

It's unfortunate that the board is barely readable. Some days I barely skim it and other days I don't bother as it's the same cast of characters who have zero impact on my buy/sell decisions. I continue to hold a substantial position and have not sold any shares.

Best of luck,
biodoc