Interferon gamma blocks Hyaluronan-CD44 bonding of T cells- it does so w/o removing hyaluronan from the ECM- so doesn't help to reduce the Intratumor pressure like PegpH20.- so 1/2 as effective. Stilll it helps lead the way in showing why PegpH20 will add to TIL effect- as it will add to TCR and CAR-T effect.
after hours perhaps- doesn't explain swimming upstream against the tide of red bios- most were in Russell,
Amgen has a deal with KITE on CAR-T - KITE has no solid tumor plan- HALO IS a solid tumor plan. AMGN has their ex CFO- K Falberg- on HALO board with 2 long term execs running HALO- 1 who colonized ONXX for them in order to acquire a potential blockbuster (Kyprolis)- I see Amgen making a try at HALO - hopefully an unsuccessful one.
Growing realization on Twitter- HALO is an immunooncology company. Hingorani paper 2014 Carcinogenesis explains- HA+CD44 Binds Teffector cells- CD8+- as in CAR-T, TIL, and TCR- releases Interleukin 10 - also suppresses T cell effect- all part of an innate system which fights autoimmune disease. CAR-T, TIL, and TCR looks to the immune system just like autoimmune disease. HALO is the next best shot at interrupting this system by reducing HA-CD44 binding of activated T cells.
Russell Rebalance- happens once a year this week. HALO is part of the Russell index.
Amen- Get us a CAR-T and there's no looking back-
ALL- CRs - no HA
Follic Lymphoma 23u HA vs DBLCL 37u HA- FL 2x better CAR-T response
Malig Melanoma- Low hA- Good TIL & Anti PD-1 Response
Panc CA- No reponse w Loss of 1/2 CAR-T Meso cells vs ALL peak levels with only 28 d duration for remainimg
ALL adds up to Response to Activated T cell Rx being Inverselty proportional to Hyaluronan Level- So PegpH20- the only avaiable Hyaluronidase working at neutral tumor levels (6.9-7.4) will be indicated to make solid car-t (and TIL, anti PD-1, & TCR) more like CAR-T for Blood Ca.
Solid Tumor CAR-T, AutoImmune Defense, And PegpH20
Jun 8, 2015 8:40 AM Fezziwig2008
Hyaluronan is a glycosaminoglycan sugar that is ubiquitous to the plasma cell membrane and tumor microenvironment. It both causes constriction of arterioles delivering blood, chemotherapy, and immunotherapy and binds Activated T cells presenting to the cell membrane. It does not bind native T cells. This binding of Activated cells is thought to be part of the body's defense against autoimmune disease. Mice lacking CD44 the Hyaluronan receptor- CD44 Knock outs show an elevated in vivo primary and in vitro secondary response to challenge with multiple antigens. This elevation is associated with reduced activation-induced cell death when compared to mice with intact CD-44.....Contd on SA
David NOT for me -
How Unstable is TapImmune Inc. (OTCMKTS:TPIV)?
by EVAN DION
June 9, 2015 Science No Comments 222 views
TapImmune Inc. (OTCMKTS:TPIV) has been concentrating on the phase-2 trials of its Folate Receptor Alpha study. Unfortunately, the company’s own financial health has not proven to be capable of bearing the burden of the study. However, TapImmune has successfully acquired the services of institutional investors, who have agreed to provide $4.93 million in near term funding. The funding is to be provided through the investors exercising their short-term warrants.
The company’s Folate Receptor Alpha study is targeted at getting the company a much needed product in the market. TapImmune’s own financial situation has been bleak, with the company reported just $1.45 million in cash, no quarterly revenues and a quarterly net loss of $981,000. TapImmune desperately needs to upgrade from a development stage company to one that manufacture drugs for the treatment of breast and ovarian cancer. There is sufficient amount of cash in hand for the company to keep moving forward, but the institutional investors would not be very patient on their short-term returns.
TapImmune with its Folate Receptor Alpha drug is planning to replace conventional cancer treatments. The company’s research is targeted at boosting the immune system, so it destroys diseased cells. As for the Phase-1 clinical trials of the company’s lead drug, the results have been promising for triple-negative breast cancer and ovarian cancer. The study was targeted at assessing the safety of the drug and the maximum dose. Fortunately, it was found to be safe and tolerable.
The injection of additional funds from the institutional investors is sufficient to get the drug through phase-2 of clinical trials, but it would not help the drug reach the market. The company would need to file for an FDA approval before the drug can finally hit the market.
my pleasure - so much going well for HALO- this board should become more substantial with time and greater interest.
I hope NOT but you can't ignore the AMGN tie now- given ONXX buyout- I think Torley knows PegpH20 has the potential to be Much bigger than Kyprolis and would resist a Buyout- especially if PD-1 Program looks positive and even more so if CAR-T Makers keep failing at Solid Tumor treatment.
South San Francisco, CA. — Aug. 31, 2011
Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that it has appointed Helen Torley, M.B. Ch. B., M.R.C.P., as Executive Vice President and Chief Commercial Officer. In her role, Dr. Torley will report to N. Anthony Coles, M.D., President and Chief Executive Officer, and will be responsible for all commercial activities related to Nexavar and the potential launch of carfilzomib, development of the company’s European commercial organization, and growth initiatives to increase commercial activities and capabilities in the United States and in Europe.
“Helen is a strategic thinker with broad operating and general management experience,” said Dr. Coles. “Her track record of successfully growing established brands such as Epogen® and Aranesp® in nephrology and of leading multiple successful product launches − including Prolia®, Sensipar®, and Miacalcin®− will be instrumental as we prepare for the potential launch of carfilzomib, our next-generation proteasome inhibitor, and the next stage of Nexavar’s growth. We will also rely on Helen’s significant expertise to expand our commercial organization internationally.”
Amgen to Buy Onyx for $10.4 Billion to Gain Cancer Drug- August 26, 2013
Dr. Torley served as Vice President and General Manager of Nephrology Business Unit at Amgen Inc. since October 2003 to 2011. She joined Amgen Inc. on June 2002 as Therapeutic Area Head of Inflammation Global Marketing.
Treasurer (Acting) and Executive Director Finance
August 2010 – March 2012 (1 year 8 months)Thousand Oaks, CA
Acting Treasurer 7/2011 - 3/2012
Executive Director, International Business Development
January 2008 – August 2010 (2 years 8 months)
Business and commercial development for international commercial operations group.
Responsibile for Amgen's Emerging Markets Expansion.
Executive Director, Finance
January 2005 – December 2007 (3 years)
Financial Planning and Analysis for the Global Commercial Organization
Executive Director, Corporate Accounting
January 2004 – December 2005 (2 years)
Director - Financial Planning & Analysis
January 2002 – January 2004 (2 years 1 month)
Manager, Sr. Manager of FP&A
January 1997 – January 2002 (5 years 1 month)Thousand Oaks, CA
"Before Shire, she spent 15 years at Amgen, in senior leadership roles in finance and business development."
Director Kathryn Falberg- the big buyer in '13- was CFO @ AMGN for 7 years:
Forbes- Top Buys by Directors: Falberg's $681.6K Bet on HALO
Comment Now Follow Comments
The directors of a company tend to have a unique inside view into the business, so when directors make major buys, investors are wise to take notice. Presumably the only reason a director of a company would choose to take their hard-earned cash and use it to buy stock in the open market, is that they expect to make money — maybe they find the stock very undervalued, or maybe they see exciting progress within the company, or maybe both. So in this series we look at the largest insider buys by company directors over the trailing six month period, one of which was a total of $681.6K by Kathryn E. Falberg, Director at Halozyme Therapeutics.
Know another company with so many ex-Amgen in leadership? Recall the Amgen exec who left for ONXX as CCO then helped deliver THEIR "Blockbuster in waiting" Kyprolis back to AMGN. It was Helen Torley.
HA Screening LESS Important now as 202 data showed no higher risk from AEs with pegpH20- in fact it was Protective of TEs! So Burden to screen mainly to show significant effect for approval- THEN- Rx more patients with PegpH20-- the alternative is Certain Death from PDA- there was a CR in PefgpH20 Group- May be more when anti PD-1 or CAR-T partnered-
"Data was also presented on the rate of thromboembolic (TE) events in 55 patients treated in stage 2 of the trial, which is currently randomizing patients at a 2:1 ratio of PAG versus AG. Stage 2 began after a protocol amendment in July 2014, excluding patients at high risk of TE events and adding prophylaxis with low molecular weight heparin (enoxaparin) to all patients in both treatment arms. Reported results included:
A TE event rate of 13 percent in 38 patients treated with PAG versus 18 percent in 17 patients receiving AG;
In the 20 PAG patients receiving 1 mg/kg/day of enoxaparin, no TE events have been reported to date."