Replies to post #267694 on Avid Bioservices Inc (CDMO)

[biopharm]

a new book is out, since March 15, 2016 and one I didn't catch... but some familiar names tied to PS Targeting research:

Quote:Comprehensively explores the biology and role of MDSCs in cancer
Covers therapeutic targeting via the STAT3 pathway, a major regulatory pathway in MDSCs functions as well as in tumour cells
Particularly relevant for scientists working in the pharmaceutical industry and in oncology research

The book starts with an introduction to and history of myeloid-derived suppressor cells (MDSCs), followed by a description of their differentiation, their role in the tumour microenvironment and their therapeutic targeting. It closes with an outlook on future developments. In cancer patients, myelopoiesis is perturbed and instead of generating immunogenic myeloid cells (such as dendritic cells, inflammatory macrophages and granulocytes), there is an increase in highly immature MDSCs. These cells are distributed systemically, resulting in general immunosuppression. They also infiltrate tumours, promoting their progression and metastasis by inhibiting the natural anti-tumour immune response. As these cells also interact with classical anti-neoplastic treatments, they have become major therapeutic targets in the pharmaceutical industry and in oncology research.

http://webcache.googleusercontent.com/search?q=cache:wZozXYA9jYYJ:www.cracketc.com/myeloid-derived-suppressor-cells-and-cancer/+&cd=1&hl=en&ct=clnk&gl=us

My first question was a book about MDSC's... WITHOUT... Dr. Dmitry Gabrilovich as first author ??

Well... digging deeper we take one author: James Talmadge and hmmm, direct connection, collaboration with Dr. Gabrilovich can be found. I guess Dr. Gabrilovich has other things to attend to and if I may say so myself... the landscape is being prepped
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James Talmadge, Ph.D.

The Laboratory of Transplantation Immunology is focused on the role of the microenvironment and host immunity during the tumor progression and metastasis, as well as, interventional strategies to augment the host response against tumors and overcome immune suppression associated with tumor growth and myelosuppressive therapy. Our research emphasizes molecular and cellular immunology, DC vaccines, stem cell transplantation, gene therapy, T-cell responses to cytokine and molecular therapeutic intervention and the role of the host response and the tumor microenvironment to tumor progression. Our clinical and translational research is focused on the tumor microenvironment including MDSCs, DCs and T-cells; and DC vaccines primarily against breast cancer and melanoma. Clinical studies have included breast cancer vaccines in collaboration with Dr. Ken Cowan and Dr. Beth Reed at UNMC, and Dr. Dmitry Gabrilovich at Moffitt Cancer Center. A current collaboration is with Intrexon Inc. with a focus on melanoma. Early-stage studies have also focused on immune recovery following stem cell transplantation, at present, primarily in collaboration with Dr. Greg Bociek, Internal Medicine, UNMC, as regards non-myeloablative, allogeneic, stem cell transplantation.

Basic/translational research studies are focused on host-tumor interactions during tumor progression, metastasis and cytoreductive therapy. We have focused on the effect of mammary tumor growth on the expansion and trafficking of MDSCs and strategies to control proliferation and function including molecular therapeutics, such as COX-2 inhibitors, tyrosine kinase inhibitors, all-trans-retinoic acid (ATRA) and VEGF inhibitors. Our current focus is on sites of proliferation using BrdU labeling in vivo, trafficking using carboxyfluorescein succinimidyl ester (CFSE)-labeled cells, immunohistochemistry (IHC) targeting Gr1, CD11b and Ki-67 with exciting observations into extramedullary hematopoiesis. Studies into the mechanism of immunosuppression have revealed critical roles for granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) and VEGF in the expansion of the MDSCs and have suggested a critical role for inducible nitric oxide synthase and arginase as regional mediators of T-cell suppression. Studies in collaboration with Dr. Shi-Jian Ding, have identified a working hypothesis that post translational modification by S-nitrosylation may have a critical role in regulating the tumor-induced inflammation observed as part of tumor progression. These rodent studies have been in collaboration with Drs. Rakish Singh and Joyce Solheim at UNMC for many productive years.

The Laboratory of Transplantation Immunology is also very active (along with many others) in the development of the Biological Production Facility, which utilizes good manufacturing practices (GMPs) for the vaccines we deliver in support of our INDs to treat neoplasia. This includes the development of new vaccine manufacturing strategies and the development and validation of release assays, and protocols including flow cytometry and ELISA assays.

http://www.unmc.edu/pathology/research/immunology.html

So many more connections to revisit... Sunil Chada, Antonia, Gabrilovich, Kerstin Menander, Intrexon.... hmmm, didn't all those shares in March 2014 trade during this patent timeframe...=>yes!

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=112091582

[Protector]

biopharm, while on one side I can agree with you that Bavituximab and BetaBodies certainly have value in Calico's goal, the combat against ageing, I have a hard time to see calico as a 'potential' party that would either acquire or be that one major partnership that PPHM would sign as a significant PPS mover.

As I am not into easy one-liners I will develop the reasoning some more giving you more material to either acknowledge or challenge because I can of course be wrong.

Bavituximab/Betabodies
Longevity no doubt includes countering all biological reasons that could lead to death and not just the extension of life. Within that reasoning part of any longevity strategy must therefor be pro-active prevention against everything that could cross any successful approach of life extension itself. Diseases are no doubt one of the causes that could spoil the soup. Furthermore DNA damage or undetected modification and mutation thereof could be part of biological countermeasures slinking in to undo or diminish the effects of the pro-longevity measures.

With Bavituximab and BetaBodies, and possibly BB vaccines, the immune system could be enabled to play shorter on the ball and counter most viral, inflectional or mutational (cancer) and physical causes of damaged cells and/or DNA. Bavituximab will, IMO, certainly not be the main Calico molecule for longevity because it doesn't do anything to prolongue your live, it rather helps preventing to shorten it. Even if you take ALL diseases and external factors such as accidents away you will still eventually die within a certain age range largely dependant on your state of fitness, food, stress etc. As far as I understood it Calico is after extending that range.

Pocket Depth
We all know that Calico is baked by powerful non Biotech/Pharma companies our there founders, board members or CEO's. People in the ITC sector have clearly assessed that there is a cause for investment here. Furthermore they understood, very certainly based on the way things are in the ITC, that they needed to go for a strong and renound team of people. You mentioned Art Levingston yourself and we know there are others. But Calico's pocket depth is meaningless compared to JNJ/J, PFE, GILD and others in the Biotech/Pharma industry. It would have to raise money, which it can and probably more easily can because the underlying parties involved, but would actually invest in a company/drug that it DOES NOT need to own or control because when available in sufficient amounts, assume later this year or at the last begin next year, they can simply buy it and combine it with whatever their main cornerstone molecule or approach for longevity is going to be.

So my conclusion for this part is that Calico doesn't have the pocket depth, could possibly raise the capital, but would make a strategically poor investment in case of some acquisition attempt IMO. And as a partner they would certainly not be THAT partner that we are all waiting for and that would move Bavituximab and BetaBodies with the needed expedition.

Collaborations
Last but not least Calico, just like BP, will be in the patent war. It will need to make deals with others to be able to use certain patents on top of its own to reach its goal. If calico becomes the owner of bavituximab/Betabodies IP and pipelines then, IMO, they clearly loose their neutrality. Today BP sees them as a neutral player because they are in no way investing in the same types of pipelines as most BPs. Even more, if people live longer then there are a large range of products that BP produces today that people that will be much higher aged then the average population of today are going to need. The simple flue vaccine for instance, but also others such as a hip replacement/transplant for instance that itself will cause the needs for anaesthetics, surgery tools, pain killers, etc.

So Calico, from a strategic point of view is better of with this neutral position if it wants easy and hands free collaborations and lasting goodwill of BP. Owning the IP and the pipelines of Bavituximab and BetaBodies doesn't seem the right move UNLESS Calico would step up and would want to pursue its goal more aggressively, for instance because even with its neutrality BP has reasons to not collaborate easily or at extreme terms or cost.

AIMO.

[vinmantoo]

Well they were always my #1 choice and if so... I think a bit of luck and Federal Investigations will have something to do with it. Till then... I wonder what Art Levinston thinks of all these researchers...

Biopharm is talking about Calico being the #1 suitor for PPHM. Now that is funny because there is a 0.00000001 chance of that happening!