Replies to post #113600 on Innovation Pharmaceuticals Inc (IPIX)

[Chemdeps]

I'm with you Chuck....a lot of catalysts coming up and I don't mind waiting until the price moves due to the science and progression of trials....recently I have been distracted from this stock due to another promising stock for AD and as a result, it has given me more patience with this one...I can wait however long it takes for the true value to arrive here...

[Rdunn88]

It's all perception... I'll gladly give up 75 percent of my shares, not lose any equity and move off the pinks... Now, some will say a RS announcement will cause the PPS to drop. Well, the PPS just dropped 10 percent on B news... Remember, they're not doing a RS because their being de-listed a big difference. Again, we will see if Leo can get the PPS higher? So far this year he's been unsuccessful. Down now 38 percent YTD... Also, would a partnership deal warrant CTIX being off-the-pinks?

[Ultimate01]

Well said!

[Qoheleth]

Chuck - you've expressed my perspective well. Thx

[alwaysdreaming]

Eggsactlly, thank you! It's only obvious that maybe initially the pps will be 2 or 3 times the presplit price, but a year or 2 down the road, is when someone with half as many shares will see the effect.

By then the promoters for the split will be long gone.

[25 Kilos of Gold]

The POST of the year. Long term patience instead of short term panic thinking.
Look at the yearly charts. Last year I was making my major buys at 1.60- 1.70 range.
The science is much further along than 11 months ago and will get rewarded in due time as it has been over the years. The O/S is low with a 40% owned by insiders.
Let Leo do his thing. He's put far more money into peoples wallets than any of the whiners ever will.

[slcimmuno]

good post. def my perspective too. the real CTIX story is the Science, and it's continuing to prove out, show real progress ... both as to Brilacidin (e.g., QIDP, thumbs up for the Ph III ABSSSI, B-OM, gram-neg analogs) and Kevetrin (e.g., Orphan Drug designation for Ovarian, Ph II AML-Bologna).

we have a New Class of ABXs that the world so needs (and imptly, one not naturally selected for resistance to develop) in a final-stage trial, and a potentially First Ever p53/mdm2 inhibitor (to the Guardian Angel idea). with Prurisol waiting in the wings.

sure, the current price doesn't reflect a fair(er) valuation, what, with the # of advanced clinical trials underway and upcoming. but the Uplist will happen, helping to bring more eyeballs, establish more Street cred so to speak (Institutions, Analyst coverage).

taking the Long view, i couldn't be more excited about the company's continuing progress to date and future prospects---barring the Black Swan event, the Science increasingly/eventually trumping all the near-term naysaying, angst.

a concrete example of why I'm excited: New Novartis research on their p53/MDM2 (wt-only) Inhibitors... (NVP-CFC218 and NVP-CGM097)... goes to the Big Time promise of Kevetrin, esp given its multimodal nature (activating wt, and mutant) and non-toxic profile, toward saving a lot of lives just as it lines R/S-free investor pockets. the latter Novartis drug is in a Ph I at Dana Farber. A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors (CCGM097X2101)
estimated enrollment: 92,
start date: March 2013,
estimated completion: June 2016

the gist of the research: the Novartis team has identified 13 biomarkers (genetic expression signatures) that predict MDM2 drug efficacy (shrinking of tumors), with a 70% accuracy.

am assuming this is squarely where CTIX is at.... mining the Ph I Kevetrin tumor data to better target therapies, ID the proper biomarkers, cancers for mono/combo therapy. right now, seems the best results they saw were in Ovarian cancers given the Orphan Drug designation, how these patients ramped up in the Ph I.

think v exciting times ahead as to Kevetrin--toward drugging what was once considered the undruggable pathway (p53).

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"A Signature of Success"
http://dx.doi.org/10.7554/eLife.08773
Published June 16, 2015

EXCERPT
Eleven years ago, the first targeted therapies that reactivate a protein called p53, which is inactivated in many cancer cells, were developed. However, in most types of cancer cells tested, restoring activity of the p53 tumor suppressor failed to kill the cancer cells. Now, in eLife, Diana Graus Porta and colleagues at the Novartis Institutes for BioMedical Research—including Sebastien Jeay as first author—describe a ‘biomarker’ that can predict whether or not different cancer cells will die if p53 is reactivated (Jeay et al., 2015).

p53 controls programmed cell death (apoptosis), the arrest of cell division and other cell responses to stress by binding to DNA and increasing the expression of particular genes (Bieging et al., 2014). However, despite decades of study, we do not fully understand how cells respond to p53 activity. Around 50% of all human cancers have mutations in TP53, the gene that encodes the p53 tumor suppressor protein, and these tumors produce inactive forms of p53. However, in the other cancers, p53 is inactivated in other ways, such as by the over-activation of MDM2 (sometimes known as HDM2), a protein that represses the activity of p53. Therefore, 11 million cancer patients worldwide have tumors with normal p53 proteins that may benefit from treatment with drugs that can inhibit the activity of MDM2.

The first MDM2 inhibitor, called Nutlin-3, was discovered in 2004. Since then, a flurry of activity in the pharmaceutical industry has led to development of several similar compounds, many of which are currently being tested in clinical trials (Khoo et al., 2014). Although these drugs are able to activate p53 and induce changes in the expression of many of the genes involved in apoptosis, this does not lead to increased levels of cell death in most types of cancer cells (Tovar et al., 2006; Garnett et al., 2012). These drugs stop the cells from dividing, but this is only a temporary effect and so is of limited therapeutic value. What factors determine whether or not a cancer cell dies when MDM2 is inhibited?

Jeay et al. describe two new MDM2 inhibitors called NVP-CFC218 and NVP-CGM097. These compounds mimic the interactions between p53 and MDM2 to prevent them from interacting with each other, which results in the activation of p53. Like other inhibitors that target the interactions between p53 and MDM2, both compounds only affect cells that carry normal p53 proteins. Jeay et al. tested the effects of both drugs on the growth of cells in 356 different cancer cell lines, and found that cells in 47 of the lines stopped growing (referred to as sensitive), but cells in 309 of the lines were unaffected (insensitive). Although all of the sensitive lines had normal p53 as expected, the majority of the cell lines with normal p53 were insensitive to these drugs. Therefore, the presence of mutations in the TP53gene alone is not a good indicator of the response of cancer cells to these drugs.

To address the need for a better biomarker, Jeay et al. compared the gene expression profiles of the sensitive and insensitive cell lines before the drug treatment. They discovered a gene expression ‘signature’ of 13 genes that can predict the response of cells to treatment with NVP-CFC218 or NVP-CGM097. After confirming the predictive power of this signature in several different cancer cell lines, they tested this biomarker in tumor samples collected from 55 patients. 19 of the 27 of the tumor samples predicted to be sensitive to the drugs decreased in size after treatment, yielding a predictive value of more than 70% (Figure 1).

Intriguingly, the gene expression signature is made entirely of genes that are known to be directly regulated by p53, which implies that there is a partially active p53 signaling pathway in the sensitive cells prior to the drug treatment. This finding raises some tantalizing questions: is this p53 activity required for cells to be sensitive, and how is it achieved? Do the sensitive cell lines have a protein that is essential for p53 activity that has been inactivated in the insensitive cells? Do the insensitive cells have another protein that inhibits p53—other than MDM2—that is lost in sensitive cells? Or, is it easier for p53 to access DNA in sensitive cells to promote gene expression? Is the p53 activity in sensitive cells a sign that the cells are experiencing stress prior to the drug treatment? Answering these questions will both advance our understanding of the biology of p53, and also help us to harness the remarkable power of p53 for therapeutic use.

As more targeted therapies are developed, it is absolutely essential that biomarkers accompany them to the market. The Novartis team describes an elegant, yet straightforward method for determining gene expression signatures that can predict the responses of cells to drug treatments, and medical researchers should consider using similar methods during the preclinical phase of the development of all new drugs. Gene expression signatures may also lead to more effective therapies that use combinations of drugs. Hopefully, the discovery of this signature will accelerate the deployment of MDM2 inhibitors into the clinic, which will benefit millions of cancer patients carrying tumors with normal p53 that has been deactivated by MDM2.

///

"A distinct p53 target gene set predicts for response to the selective p53–HDM2 inhibitor NVP-CGM097"
DOI: http://dx.doi.org/10.7554/eLife.06498
Published May 12, 2015
Cite as eLife 2015;4:e06498

ABSTRACT
Biomarkers for patient selection are essential for the successful and rapid development of emerging targeted anti-cancer therapeutics. In this study, we report the discovery of a novel patient selection strategy for the p53–HDM2 inhibitor NVP-CGM097, currently under evaluation in clinical trials. By intersecting high-throughput cell line sensitivity data with genomic data, we have identified a gene expression signature consisting of 13 up-regulated genes that predicts for sensitivity to NVP-CGM097 in both cell lines and in patient-derived tumor xenograft models. Interestingly, these 13 genes are known p53 downstream target genes, suggesting that the identified gene signature reflects the presence of at least a partially activated p53 pathway in NVP-CGM097-sensitive tumors. Together, our findings provide evidence for the use of this newly identified predictive gene signature to refine the selection of patients with wild-type p53 tumors and increase the likelihood of response to treatment with p53–HDM2 inhibitors, such as NVP-CGM097.

///

"Discovery of a dihydroisoquinolinone derivative (NVP-CGM097) - a highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumors." [this is likely the kind of article we'll see written up for Kevetrin at some point]
http://www.ncbi.nlm.nih.gov/m/pubmed/26181851/
http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b00810

ABSTRACT
As a result of our efforts to discover novel p53-MDM2 protein-protein interaction inhibitors useful for treating cancer, the potent and selective MDM2 inhibitor NVP-CGM097 (1) with an excellent in vivo profile was selected as a clinical candidate and is currently in phase 1 clinical development. This article provides an overview of the discovery of this new clinical p53-MDM2 inhibitor. The following aspects are addressed: mechanism of action, scientific rationale, binding mode, medicinal chemistry, pharmacokinetic and pharmacodynamic properties and

[muelch]

The stock price of CTIX is going to grow based on the outcome of the science not the market cap.

No offense but this is the kind of thinking from investors that is the reason why we need to move off of the OTC.

Penny stocks are a lot like penny slots. They have the worst payout. You can lookup a lot of OTC statistics, they're horrifying. People are mislead because they are cheap and can have large payouts, but the average return is still negative (a casino is one thing, but that's a pretty terrible property to have for an investment).

Maybe out here in penny land do investors care about mostly arbitrary metrics such as share price. The big boys care about P/E, P/S, market cap, cash burn rates, and other statistics that have nothing to do with how many shares a company has or what the share price is. To some degree they also care about share price to avoid having enough/too much liquidity, and that range is above what CTIX currently trades at.

Long term, the share price and outstanding shares in and of themselves do not matter, only market cap will matter. The growth of the market cap is the only thing that will increase your return. A large pharmaceutical company might one day pay $10B for Cellceutix based on revenue projections, and that's what our market cap will become, and that's what your return will be based on.

Your argument is like saying: "Assume Cellceutix's market cap will one day be $8B shortly before a buyout. If we do a r/s, it will instead be $4B shortly before a buyout. When the buyout comes, the premium paid will be the same regardless."

That shouldn't be what happens. It would be an arbitrary factor of two difference in our P/E ratio if we were to market our drugs ourselves. If the company is worth $10B in a buyout scenario, then that's what should be paid. One could make the argument that Cellceutix is in a better bargaining position the closer their market cap is to that buyout number, but that's quite a few assumptions to make. If our revenue is worth $10B to someone, then that's what they're willing to pay.

So no, growth of share price is not based on future value of the science, it's based on revenue and earning projections which will dictate things like P/E and our market cap.

Unlike the reasons for not doing a r/s (i.e. arbitrary perception), the reasons for doing a r/s are very tangible. We've had millions of shares dumped into the market from Aruda, or could have. Those shares would be much more readily absorbed if we were trading on the Nasdaq. Some believe there'd be less manipulation, which erodes sp. Investors wouldn't be deterred from investing long due to trading on the OTC (the OTC is a huge deterrence). All this leads to a higher market cap. Cellceutix needs to finance its operations, the longer we remain at an artificially lower sp than need be means more shares have to be sold to Aspire to raise the same amount of equity. This increases dilution, and results in a very tangible reduction to your return.