On Sunday December 23rd, 2012, I saw a front page article in The New York Times by Gina Kolata titled "A Single Drug To Kill Cancers In Many Forms." Kolata said, "For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of the organ where the cancer originated--breast, brain, prostate, liver, lung or kidney. The drugs go after an aberration involving a cancer gene, p53, fundamental to tumor growth. Many scientists are seeing this as the beginning of a new genetic age in cancer research."
Who are the three companies mentioned as "racing" to develop separate versions of these blockbuster therapeutics for many forms of cancer? Merck (NYSE: MRK), Roche (OTCQX:RHHBY) and Sanofi (NYSE: SNY). According to Kolata, it seems those three are the companies most deserving of national recognition. However, if Kolata would have looked a little deeper, she might have found reason to mention Pfizer (NYSE: PFE).
And where has this research on p53 been conducted? For Roche in Europe; for Merck in the United States; and for Sanofi in the US at the University of Michigan. To Kolata's credit she succinctly summarized the history of the p53 science as beginning about 20 years ago, being feted as the molecule of the year by Science Magazine in 1993. Kolata described Roche's comprehensive and aggressive research from 1996 to 2002, in a valiant attempt to take the costly science and translate it into a compound that it could test in humans. The key word for this 6-year research era was "Nutlins," the discovery of a small molecule that could enter the small opening between the MDM2 and the p53 and pry them apart. Kolata properly summarizes that Nutlins were simply unable to be absorbed by the human body and therefore Roche's big investment was not able to be considered as a potential for human trials. Simply put, Roche developed a cancer cure for mice, but not for humans.
NYTimes readers would probably conclude that Kolata's article presents itself as a survey of the current race for oncolytic p53 compounds with broad therapeutic indexes. Roche recently finished an FDA phase 1 for RG 7112. The compound was not tested against "many forms of cancer," but for leukemia. Roche is waiting for evident cause to begin an FDA phase 2 efficacy test for this p53 compound. Sanofi/Ascenta and Merck are indicated by Kolata to soon begin FDA phase 1 trials and will form patient safety data to determine if there is justification for FDA phase 2. Based upon Kolata's coverage, there is very little that appears promising near term (1-18 months) for an investor in the race for a p53 compound. Kolata's mention of the University of Michigan is worthy, however, her omission of Beth Israel Deaconess and Dana Farber are points for head scratching. Yet when the missing elements are added to Kolata's article, there is a substantial near-term promise.
Conspicuously absent from Ms. Kolata's purported survey of p53 development history, research, and current p53 therapeutic FDA trials is a company named Cellceutix (OTCQB:CTIX) that is clinically testing Kevetrin, arguably the lead compound in the p53 therapeutic race. Ironically, Cellceutix' Kevetrin is the only p53 therapeutic compound that is currently doing what Ms. Kolata's title suggests, namely "being tested against many forms of cancer."
If Kevetrin was yet in preclinical testing, one could understand why Kolata would not mention it in her article. However, Cellceutix' Kevetrin is in FDA phase 1 trials, having begun its second cohort, doubling the initial dosage at Dana Farber in December 2012. Kevetrin is the lead therapeutic in the p53 drug race. Perhaps one can rationalize Kolata's nescience as a form of blue chip prejudice, whereby a news organization can only show public respect and acknowledge notable achievements of large public companies like Merck, Sanofi or Roche. Even if this is so, Kolata should have mentioned Cellceutix if her article was to be a survey of the p53 therapeutic race. Cellceutix happens to be a public company with a very small capitalization when compared with the large pharmaceutical companies. Not the type that Harvard's Dana Farber embraces for clinical testing. That's an accomplishment to herald Cellceutix, not a reason to shun Kevetrin. On May 25th, 2011, Cellceutix announced that Kevetrin displayed superior p53 oncolytic characteristics to that of Sanofi /Ascenta's p53 drug because it seems to work on both wild and mutant p53.
In early October of 2012, GlaxoSmithKline (NYSE: GSK) reported on a study that they sponsored pitting their drug Pazopanib against Pfizer's Sunitinib. The survival rates of patients taking each of the renal cancer drugs were similar at approximately 10 months. However, the GlaxoSmithKline compound Pazopanib had fewer side effects and they occurred less frequently, making it superior to Sunitinib in the quality of life category. Citigroup analyst in London, Andrew Baum, echoing the quality of life issue, stated that the comparative data on Pazopanib vs Sunitinib "will likely allow GlaxoSmithKline to take renal cancer market share away from Pfizer's Sunitinib. With this agreement and the support of ongoing preclinical studies, Pfizer and Beth Israel can test Sunitinib and Kevetrin together in renal cancer patients. I believe that testing would provide clinical evidence that the p53 activating Kevetrin/Sunitinib conjugation will produce a substantially improved life span perhaps with no side effects beyond those already associated with Sunitinib. Of course, it is speculative to make this prediction, but I surmise that combination therapies utilizing a p53 drug like Kevetrin that has shown efficacy in animal models and is completely novel to the human body can extend the life of cancer patients longer than the normal ten months. Kevetrin is moving toward MTD (maximum tolerated dosage) within its FDA phase 1 trial at Beth Israel's sister hospital, Dana Farber. Pfizer and Beth Israel will soon be able to test Sunitinib and Kevetrin together in renal cancer patients. There is already preclinical evidence that indicates that a turnaround for Sunitinib is in the works. Should the conjugation clinicals with Beth Israel/Pfizer and Bologna/(Roche?) be successful with robust data, we will have the makings of a strong case for the FDA to enthusiastically sanction broadened use of conjugated Kevetrin. The successful conjugation of Kevetrin with an approved drug could be a catalyst for the FDA to accelerate broader human utilization.
The annual market for Renal Cancer drugs is expected to be 3 billion dollars by 2017. A conjugation of Sunitinib/ Kevetrin could be the market share game changer for Sunitinib vs. Pazopanib. For the near term, GlaxoSmithKline's Pazopanib is the primary multikinase inhibitor in the renal cancer market. So presumably Glaxo's Pazopanib would probably make a better conjugation with Kevetrin than Sunitinib. Credit must be given to Beth Israel and Pfizer for maneuvering into position with Cellceutix and Kevetrin first. Cellceutix and Pfizer shareholders should watch carefully for any patient results in the FDA 1 trials at Dana Farber for mention of any renal cancer patients. Also, we should be alert for any news about preclinical studies leading to planning of clinical trials of the Pfizer / Beth Israel straddle conjugating Kevetrin with two of Pfizer's multikinase inhibitors. Those trials could gain an advantage through knowledge from the initial clinical trials ongoing now against solid tumors, as Beth Israel should be able to begin their clinical near MTD levels of Kevetrin. Andrew Baum, and all of the other investors and analysts that follow the GlaxoSmithKline vs. Pfizer multikinase inhibitor competition need to evaluate p53 activating Kevetrin prior to resigning that GlaxoSmithKline's Pazopanib is going to continue to take and retain market share from Sunitinib. Certainly, Beth Israel and Pfizer, along with Harvard's Dana Farber and Cellceutix deserved mention in Ms. Kolata's article for this and many other reasons. Cellceutix has no expenditures in the Beth Israel clinical other than to provide Kevetrin.
The European University of Bologna is readying to conduct a Phase 1b trial pitting Kevetrin against Acute Myelogenous Leukemia (AML). Additional information there, coupled with data from ongoing trials, could lead to the hospital boldly reapply for Kevetrin to enter FDA 2 trials in Europe. This will pave the way for Kevetrin to be compared and contrasted to Roche's RG7112 p53 activating compound. As I connect the dots to determine the identity of the unidentified International Pharmaceutical involved with The University of Bologna, I believe that it's Roche. Even if it's not Roche, Cellceutix shareholders have the comfort of knowing that two major international pharmaceuticals will either begin a bidding war for Kevetrin, form a three way partnership with Cellceutix or walk away.
If one considers Kevetrin's inventor, Dr. Krishna Menon, the impeccable scientific advisory board and the recent announcement of a Southwestern US Cancer Research and Treatment facility intending to fund research with Kevetrin on myeloma patients, it becomes evident that Kevetrin is attracting premier interest and research investment from the most prestigious areas of oncological enterprise. The fact that so many prestigious scientific institutions want to spend multi-millions of dollars researching Kevetrin in humans in conjunction with other oncolytic compounds is a compelling accretive factor for investors to consider.
Prior to the end of 2013, at the current time schedule event trajectory, Kevetrin should be tested in humans against solid cancers and hematological cancers, all of them at maximum therapeutic dosage. If Kevetrin is both non-toxic and effective in these areas of unmet need, then 2014 could be a year of positive upside status for Kevetrin and Cellceutix shareholders.
By way of describing the coming paradigm shift in charitable cancer giving from specific organ focus such as lung, kidney, liver, prostate, and brain to that of cancer giving in general, Kolata uncovered the paradigm for understanding the commercial therapeutic p53 compound revolution. Instead of having a multi-billion dollar blockbuster for one or two organs or system-focused oncolytic therapeutics, a p53 activating therapeutic should be able to effectively treat cancer over the range of the entire body. The commercial realization of this type of dynamic is that one p53 activating compound might have substantial therapeutic impact upon 50% or more of all cancers (blood, solid tumor, brain and skin). Should such be the case, then an annual market for this type of a compound would be many multiples of organ or system-specific multi-billion dollar oncolytic blockbuster therapeutics of today.
The previously discussed Sutinindab vs. Pazopanib, though significant, now shrinks in comparison. Because of Kolata's projection of the charitable giving transition, and her focus upon the three giants Merck, Roche and Sanofi, it does not feel so odd to imagine that one of those three companies could develop a p53 activating oncolytic compound that might capture 10 billion dollars a year of the cancer therapeutic market. However, when a tiny company like Cellceutix has the best and most advanced compound in the race for a p53 activating cancer drug, the powerball-like potential of its common shares can seem too good to be true. I am just apprehensive about indicating that a 10 billion dollar annual oncolytic market is possible inside of such a small company. If you Google p53 next to a variety of other diseases like benign tumors, HIV and AIDS-related cancers, Sickle Cell Anemia, Hepatitis, Tuberculosis and others, you will surmise that a compound that could activate p53 and p21 as Kevetrin portents without toxicity could become one of the most broadly cocktailed and conjugated therapeutic compounds known to the pharmaceutical industry. If such happens I will leave the total market estimation for Kevetrin to more worthy biotech analysts.
Where are Cellceutix shares headed? With Kevetrin alone it's obvious that I expect double digits sometime in 2014. If you add KM-133 (Prurisol) and a successful FDA 2/3 later this year as a new psoriasis treatment candidate, we could see double digits this year. Cellceutix is in a time event trajectory with both Kevetrin and Prurisol. Prurisol should be valued drastically different within 70 days after it begins FDA phase 2 / 3 in May to June of 2013. Also during the September to November corridor there could be human safety and efficacy data available from FDA phase 1 with Kevetrin. So I am looking for either an explosive or discouraging result at the end of the third to mid fourth quarter of 2013. Cellceutix shares could either crater or soar to high single or low double digits. I figure that every billion dollars of revenue that the company is perceived as capturing will translate into approximately $3.50 in fully-diluted share price. The same billion paid as licensing fees or structured product buyouts is worth more per share. Therefore, if Kevetrin is declared as both safe and effective, I would expect the Cellceutix capitalization to range between $600 million and $1 billion. The prior is just the beginning. If Prurisol clears FDA phase 2 / 3 we could be looking at the addition of another billion dollars of either near term revenue or products buyout. So you have the strong possibility of moving Cellceutix shares into double-digit status during 2014. Whenever Cellceutix believes that the FDA has allowed clinical trial information to be released regarding either of its lead compounds being safe and effective, shortly thereafter I predict that application will be made by the company to list on NASDAQ.
Yes, Kevetrin has its skeptics and rightfully so being yet in the first half of its FDA 1 trial. However, within 18 months we should have human data on Kevetrin acting upon blood and solid tumor cancers. Prurisol is perhaps going to eclipse Kevetrin in both value and profile sometime in the third to fourth quarter 2013. We are going to know a lot more about both compounds very soon. There will be volatility and winning trades will probably be made in Cellceutix shares both short and long. However, I believe that the longs will win big because I think Kevetrin will win "The Amazing P53 Drug Race" by a substantial time, safety and efficacy margin