Cytokine interactions

Friday, March 18, 2016

Anticancer drug development: Gilead a force of capital and brains

Friday, March 18, 2016 | By Amirah Al Idrus
Lifted from Fierce Tech pubs

Gilead Chief Scientific Officer Norbert Bischofberger

As competition for its hepatitis C drugs intensifies, Gilead Sciences ($GILD) has been working to build up in other therapeutic areas, especially cancer. And while a painful clinical failure for the blockbuster hopeful Zydelig and the high-profile departure of oncology head Philippe Bishop have hamstrung those efforts, Gilead is bullish about its future in the field.

Zydelig got an FDA nod in 2014 for three kinds of blood cancer, but serious side effects--including death--have halted 6 trials using the drug in combination with a variety of others as a first-line therapy. Gilead said it would stop its programs investigating the drug as a first-line treatment, effectively closing one avenue of growth for Zydelig and compelling the company to look elsewhere.

Despite the setback, Gilead's Chief Scientific Officer Norbert Bischofberger is optimistic about the company's future in oncology, TheStreet reported. The Big Biotech has long said it's open to deals large and small in the space, and Bischofberger offered some clues to its strategy, telling TheStreet that Gilead is looking for novel approaches to immuno-oncology in lieu of playing catch-up with Merck ($MRK), Bristol-Myers Squibb ($BMY), which have commercialized treatments that fight tumors by blocking the protein PD-1.

"Strategically, what we want to do, instead, is to ask the question: What is it about the 70% to 80% of people that don't have a response to anti-PD-1 therapy?" Bischofberger told TheStreet's Adam Feuerstein. "We're absolutely very interested in immuno-oncology, but only if it is a truly differentiated compound from what is on the market or in late-stage clinical studies."

Gilead CEO John Milligan

Although sales of Sovaldi and Harvoni are forecast to flatten, the duo has raked in buckets of cash--$4.89 billion in the fourth quarter--which has analysts repeatedly asking just what Gilead is going to buy next. After all, the company struck gold when it acquired Pharmasset in 2011 for about $11 million and won approval for its lead hep C drug, Sovaldi, within two years.

And while new CEO John Milligan has highlighted other possible acquisition targets--inflammatory diseases and liver diseases--the fact that Gilead is trying to replace Bishop suggests that it's not exiting oncology anytime soon.

Thursday, March 10, 2016

CCR4 Antibody . WHAT ARE THE CYTOKINE RESPONSES?

LIFTED FROM FIERCE PUBLICATIONS

2. With $70M in VC cash, Tizona takes a fresh approach to immuno-oncology

Tuesday, March 8, 2016 | By Damian Garde

South San Francisco biotech Tizona Therapeutics is coming out of stealth with more than $70 million raised through two funding rounds and a pair of projects it believes can stand out in the fast-moving field of immuno-oncology.

Pablo Cagnoni

Led by Onyx Pharmaceuticals veteran Pablo Cagnoni, Tizona just wrapped up a $43 million B round co-led by Abingworth and Canaan Partners with help from Lightstone Ventures and a pack of prior investors. The latest funds pile onto a previously unannounced Series A, which totaled roughly $27 million and brought together MPM Capital, Amgen ($AMGN) Ventures, Astellas Venture Management and InterWest Partners.

That cash will keep the doors open for about two years, Tizona said, and the biotech is pressing forward on two immunological targets with applications in cancer.

The first is an antibody for the CCR4 protein, designed to modulate the regulatory T cells that help cancer skate past the immune system. Other agents in immuno-oncology have proven effective at releasing the brakes on effector T cells to help the body fight malignancies, but the micro-environment surrounding tumors remains highly immunosuppressive, Cagnoni said. Blocking CCR4, the company believes, can deplete the regulatory T cells, or T-regs, that protect cancer cells in that micro-environment, making Tizona's antibody a potentially potent part of a one-two punch in oncology.

The company's second disclosed candidate is an antibody against interleukin-35, a protein secreted by T-regs to tamp down immunological response. Tizona's ambitions in IL-35 are two-fold: The biotech is at work on an antibody that can block it and thus help the body fight cancer, while at the same time crafting an IL-35 booster that could help slow down the inflammatory process in autoimmune disorders like Crohn's disease.

Tizona said it's on track to get its CCR4 therapy into clinical trials next year, and the company hopes to get one new treatment into Phase I each year thereafter. Behind its CCR4 and IL-35 candidates, the company has three more as-yet-undisclosed projects, Cagnoni said.

To get there, Tizona is planning to double its current staff of 13, scouting for talent as it builds out its pipeline. Tizona's plan is to take its candidates as far as that $70 million will take them, after which the biotech will look to either raise more money or extend its runway through a partnership, Cagnoni said.

Cagnoni took the reins at Tizona last year following a stint as president of Onyx Pharmaceuticals that concluded after Amgen completed its $10 billion acquisition of the company. Before that, Cagnoni served as head of clinical development at Novartis' ($NVS) oncology division, playing a role in the successes of Afinitor, Exjade, Glivec and other cancer treatments.

In leaving the world of big-time drugmakers for the startup scene, Cagnoni joins a growing group of pharma expats who have decamped to lead smaller companies in recent years. Former AstraZeneca ($AZN) R&D boss Briggs Morrison followed a similar path when he took over Syndax ($SNDX), as did ex-Merck KGaA research chief Annalisa Jenkins at Dimension Therapeutics ($DMTX) and one-time Biogen ($BIIB) R&D leader Doug Williams at Codiak BioSciences.

But "it's not about big versus small," Cagnoni said. His experience with companies whose payroll measures in the thousands was "invaluable" as Tizona came together, even if he's still getting used to handling his own literature searches.

"In a small company, you have to do certain things you haven't done in a while," Cagnoni said. "But at the same time, the amount of time you spend in a large company on decisionmaking bodies, restructurings, off-site--I'll take fixing the paper jam any day."

Saturday, January 25, 2014

Male Chorus-How Excellent, Hamilton Park Baptist- Dallas

Saturday, November 30, 2013

Pregnancy Labor and Cytokines

Ultimately speaking there is either a Th1 or Th2 bifurcation in the disease T-cell prototype allowing a typical manifestation all of which is controlled by the antigen presenting and its chronicity. HIV for example has a predominant Th2 profile whereas Multiple Sclerosis is manifested as Th1 . The cytokines manifested are different in each

Doc Pete

If you are suffering from anything as far as disease is concerned, you do not need your doctor to Google the disease + cytokines involved. I will be very happy to discuss with you the implications and most up to date treatment with monoclonal antibodies against overactive cytokines and their receptors.

Doc Pete

Look out . Even birth itself is controlled by the release of the inflammatory cytokines IL1, IL6 and TNF . Of course the baby's nervous system controls all this by the proper timing and release of Substance P (necessary for the cytokine cycle). See the blowup of the 1984 model I put forth. Birth is not on there. Read
http://bit.ly/1cdWEQn

Surfactant Protein-A (SP-A) Selectively Inhibits Prostaglandin F2α (PGF2α) Production in Term...

jcem.endojournals.org

Context:Labor is characterized by “decidual activation” with production of inflammatory mediators. Recent data suggest that surfactant protein-A (SP-A) may be critical to the onset of labor in mice. Whether this is also true in humans is unclear.