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CHM, >> CTIX <<


Today's article from 'Company Spotlight' (Baystreet.ca) appears to mainly be a paid for promotional piece, coordinated to come out the day after the CTIX press release. The article does contain some other useful info on other programs beyond CTIX's, but CTIX management have historically been on the hypey side of the spectrum, compared to say Cortex. But they're not as bad as some other small bios. Most likely these recent press releases are setting up a financing.



>>> p53, Immunology and Antibody Drug Conjugate Therapies Bringing More Powerful Weapons to Battlefield in the War on Cancer



January 21,2015



http://ir.baystreet.ca/article.aspx?id=57&1421840000




War has been declared on a great many things: a war on poverty, a war on illegal drugs, a war on terrorism, etc. It has been about four and a half decades since President Richard Nixon and Congress declared war on cancer with the National Cancer Act of 1971. Hundreds of billions of dollars in government and privately-funded research later, there have been significant improvements in some treatments, diagnostics and prophylactics, but cancer is closing the gap with heart disease and held as the number two cause of death in the U.S. as reported by the CDC. Backstopped by a library of data collected over decades, scientists are making advancements with understanding the mechanics of what causes some cancers at a molecular level and slowly addressing the grand challenge of developing new treatments used in combination or independent of legacy therapies (i.e. surgery, chemo, radiation). While a “cure” for cancer is likely off on the horizon, there is a great deal of hope for more efficacious, less toxic treatments in the near term with strides being made in the areas of p53, immunotherapy and antibody-drug conjugates. In war-speak, these therapies are entering the battlefield, bringing boots on the ground, smart weapons and a general to lead an assault on tumors.

A long-heralded area of interest in oncology is p53, a tumor suppressor protein encoded by the gene TP53 coined the “Guardian of the Genome” because of its role in controlling cell cycles by enabling the repair of damaged cells or triggering their death (apoptosis). Cancer cells proliferate in part because they block or trick the body’s immune system from recognizing and attacking them, forming the foundation of immuno-oncology. They also affect p53, abrogating the pathway (wild type p53) or causing mutations (mutant type p53) in nearly every form of solid or liquid tumors so the key protein doesn’t perform its duties as commander sitting atop the cell cycle defense hierarchy. With that enormous potential patient population, p53 has for years been one of the most well known, but largely untouchable, targets in oncology. There’s been limited progress since a wider knowledge base of p53 started being constructed in the late-1980’s, but advancements seem to be accelerating in recent years.

Two notable leaders in this space are smaller companies by Wall Street standards. Privately held Aileron Therapeutics is hoping to advance its ALRN-6924, a stapled peptide believed to target the p53 tumor suppressor proteins MDM2 and MDMX, into the clinic this year. Cellceutix Corp. (OTC: CTIX) (the Company announced it intends to uplist to NASDAQ) is nearing the completion of a Phase 1 trial against solid tumors for Kevetrin, a novel small molecule shown in extensive pre-clinical research to promote p53 activation in a lengthy list of tumor types. The trials are being hosted at the venerable cancer hospitals Harvard Cancer Center’s Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center. Elsewhere, the University of Bologna is waiting for the trial to determine the maximum tolerated dose of Kevetrin before setting its dosing protocol and commencing a Phase 1/2 trial of Kevetrin in combination with cytarabine in patients with acute myelogenous leukemia (AML).

Reports from the trial have been impressive, showing Kevetrin to be well tolerated and non-genotoxic (doesn’t damage healthy DNA). Importantly, news this week detailed a dose-dependent increase in the p21 biomarker and a metastatic lesion in the spleen of a stage 4 ovarian cancer that has “disappeared,” an almost unheard of event in an early trial of such a hard-to-treat cancer.

Breakthroughs in immunotherapy go back more than 50 years with research on the cytokine interleukin-2 serving as part of a foundation for the potential to find an answer to cancer. A narrow therapeutic window and toxic side effects slowed development of immunotherapies to a certain extent, but advanced research and a better understanding of the mechanisms of cancer have it once again in the forefront of scientists and investors alike as companies compete to bring new products to market. The list of headliners in this space include those with FDA-approved drugs like Bristol-Myers Squibb (NYSE: BMY) with its immune checkpoint inhibitor Opdivo (nivolumab), which was recently approved for melanoma and demonstrated a survival advantage over the chemotherapy docetaxe in a pivotal lung cancer trial, and Merck (NYSE: MRK), who already has its PD-1 inhibitor Keytruda approved for melanoma and intends to file with the FDA later this year for expanded use of the drug in lung cancer.

While these companies are targeting PD-1, a protein that prevents the body's immune system from attacking cancer cells, smaller companies like Kite Pharma (NASDAQ: KITE) and newly-public Juno Therapeutics (NASDAQ: JUNO) are seeing significant increases in valuation due to holding a leadership position with novel chimeric antigen receptors (CAR)-T therapies. In fact, Credit Suisse this month maintained its “outperform” rating on Kite and boosted its price target from $34 to $71, citing the successful Juno IPO and Kite’s strong showing at the American Society of Hematology (ASH) conference as signs of “sustained investor and physician enthusiasm for new immune-based and personalized therapies.” Coupling the excitement with Kite planning to move into multiple late-stage trials this year, Credit Suisse thinks that a “lucrative ex-US partner is likely.”

A promising area of immunotherapy is called adoptive cell transfer, which involves engineering a patient’s own immune cells to recognize antigens and attack tumor cells. In Kite’s platform technology, dubbed eACT (engineered Autologous Cell Therapy), a patient’s peripheral blood T cells, the killer cells of the immune system, are manufactured ex vivo and infused back into the patient, essentially sending an expanded army after tumors. The re-administered cells are genetically engineered to produce special receptors on the surface called either T cell receptors (TCR) or CARs, which recognize target antigens on cancerous tumors and become activated upon engagement to selectively eradicate the tumor cells.

Kite’s therapy is showing its potential in several clinical trials being conducted by its collaborator, the Surgery Branch of the National Cancer Institute, and has attracted the attention of big pharma, including a partnership earlier this month with Amgen that entitles Kite to an upfront payment of $60 million, R&D funding and eligibility for up to $525 million in milestone payments. Already with $195.4 million in corporate coffers at the end of the third quarter, Kite is in an optimum position to advance its pipeline. The lead CAR program is a mid-stage trial of KTE-C19 for treatment of B-cell Lymphoma. There is a great deal of interest in this indication because Kite’s modified T cells are homing in on CD19, a hallmark protein expressed on the cell surface of B cell lymphomas and leukemias where there are currently very few effective therapeutic options. Elsewhere in the pipeline, data from a Phase 1 clinical trial showed that administration of anti-CD19 CAR T cells resulted in a 70% complete response rate in 20 pediatric or young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL). This year, Kite says it plans to advance KTE-C19 into pivotal trial for the above indications as well chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) in addition to therapies in its TCR eACT program for various cancers.

Another area of significant interest is the antibody-drug conjugate (ADC) business, where scientists are coupling a monoclonal antibody with cytotoxic drug and unleashing the lethal combo to seek and destroy tumors with the hope of little collateral damage to healthy tissue, a smart bomb of sorts. Wyeth, who was later acquired by Pfizer (NYSE: PFE), brought the first ADC drug to market in 2001 with Mylotarg for AML, but it was removed from marketing in 2010 due to increased risk of death and non-superior results to other AML drugs. As it stands today, only two FDA-approved ADC drugs are on the market: Seattle Genetics’ (NASDAQ: SGEN) Adcetris for both Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) was approved in 2011; and Roche (OTC:RHHBY)/Genentech’s Kadcyla for HER2-positive breast cancer who fail to respond to some other treatments was approved in early 2013. Both drugs have black box warnings in the U.S.

At the backbone of Seattle Genetics’ (or “Seagen” for short) ADC technology are linkers that have been shown in lab work to be up to 10 times more stable in the blood than conventional methods for attaching cytotoxic agents to antibodies. A key for the company is going to be expanding the approved indications for Adcetris, something that Roche just struggled to do with Kadcyla in partnership with ImmunoGen (NASDAQ: IMGN). Positive data from several studies were disclosed recently by Seagen, including results from a Phase 3 study on Adcetris, which targets the CD30 protein for treating Hodgkin lymphoma patients at risk of disease progression following autologous stem cell transplantation. Adcetris-treated patients had an “unprecedented” 50% higher chance of progression-free survival at two years compared to placebo. Separately, follow-up data from a Phase 2 trial presented at the ASH meeting showed Adcetris-treated patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) had a four-year survival rate of 64%, progression-free survival of 20 months and a median overall survival of 55.1 months. Seagen is also targeting B-cell malignancies (a la Kite in one trial, pointing its antibody at CD19).

Through its partnership with Takeda to develop and market Adcetris, Adcetris is sold in 47 countries (SGEN in the US and Canada, Takeda in the rest of the world). Through the third quarter of 2014, Seagen sales of Adcetris were up to $131.7 million from $106.1 million in the year prior period. For the full year, SGEN raised its US and Canadian sales outlook for Adcetris to a range of $172 million to $177 million. Like so many young companies, Seagen is still operating in the red, with a net loss through Q3 of $49.5 million.

Sales and $339 million in the bank are helping SGEN develop the most robust ADC drug pipeline in biotech with an array of antigen targets and synthetic cytotoxins being bound together for treating a spectrum of disease. The company has partnerships with many top pharmas, including AbbVie (NASDAQ: ABBV), Genentech, Bayer, Pfizer, GlaxoSmithKline (NYSE: GSK) and now Bristol-Myers Squibb, which will combine Adcetris with Opdivo. These collaborations put $4.5 billion on the table in potential milestone payments for Seagen if they can successfully move products forward. Insiders have made large buys recently and some analysts with much higher price targets are saying the shares of SGEN are at an unwarranted year-and-a-half low due in part to perceived competition from drugs, such as PD-1 inhibitors.

Finding a single silver bullet to destroy cancer is a misconception; it’s going to take an arsenal. More fighters moving trench to trench with smarter weapons to flesh out the enemy under the order of a fully functioning commander are substantial steps in the right direction to win this so-called war on cancer. It’s already clear that companies are quickly joining forces with the combination of their therapies as the competition is heating up, underscored by the incredible revenue potential for successful, next generation technologies. It’s been said that there is no real winner in a war, but in this case there can be many, including companies, shareholders, the scientific community and certainly cancer patients. We’re not there, but let’s hope we are moving a little closer to that horizon with these new approaches.

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