Replies to post #278797 on Avid Bioservices Inc (CDMO)

[cjgaddy]

12-8-16: Freimark/Hutchins Poster at Annual SanAntonio-Breast-Cancer-Symposium, “PS-Targeting Enhances Anti-LAG3 in Murine Breast Cancer Tumors”

Dec6-10 2016: “39th Annual San Antonio Breast Cancer Symposium”
“...presented by the Cancer Therapy & Research Center at UT Health Science Center San Antonio, AACR, and Baylor College of Medicine. The driving force behind this collaboration is the shared mission of the organizations to advance progress against breast cancer. As exciting strides are made in the field of breast cancer research & treatment, our program continues to present essential up-to-the minute info. combined with engrossing discussion for basic, translational, and clinical cancer research professionals.
SABCS'16 is designed to provide state-of-the-art info. on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer & premalignant breast disease, to an intl. audience of academic, private physicians, and researchers. We anticipate 7,500 attendees from more than 90 countries.”
http://www.sabcs.org
https://www.sabcs.org/Program/Poster-Sessions/Poster-Session-2
TRACK: Tumor Cell & Molecular Biology: Immunology & Preclin. Immunotherapy
12-8-16 7:30–9:00am Poster Session 2
#P2-04-12: “Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances the Activity of Immune Checkpoint Lag3 Targeting Antibodies in Murine Breast Tumors” - Gray MJ, Gong J, Jeff Hutchins, Bruce D. Freimark (Dir.Res/Preclin.Oncology) - Peregrine Pharmaceuticals

[cjgaddy]

12-7-16/WED/10am: Jedd Wolchok/MSKCC Lecture: "Combination Checkpoint Blockade"

12-7-16/WED 10am: Jedd D. Wolchok, MD/PhD(Mem. Sloan Kettering)
Lecture: "Combination Checkpoint Blockade" (free to public)
Location: The Wistar Institute, Philadelphia (Jedd D. Wolchock: Chief of Melanoma & Immunotherapeutics Service, MSKCC)
https://www.wistar.org/events/2016/12/combination-checkpoint-blockade

We don’t know if Dr. Wolchok will mention Peregrine/Bavi in his talk (North40000/Eb0783/Wook will let us know!), but RECALL that on 11-14-16, Dr. Wolchok’s MSKCC Lab Team, jointly with PPHM Scientists, presented a poster on Triple Combo Rad+Bavi+aPD1 vs. Melanoma:
...11-14-16: Dr. Jedd Wolchok states, “Based on these study results, we believe that the targeting of PS is having meaningful activity within the tumor microenvironment in the B16 melanoma model. It appears that this activity creates a more immune active environment in which other treatments, including radiation, are able to have a greater anti-tumor impact." See: http://tinyurl.com/js3fca4
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8

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Dec7/WED: WCLC’16 - IASLC’s 17th World Conf. on Lung Cancer, Vienna, Austria http://tinyurl.com/z8cq8vx
…2:30-3:45pm UTSW’s Dr. David Gerber to present addl. Biomarker data from Ph3.SUNRISE Trial: “A Pre-Treatment Serum Test Based on Complement & IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel”

Dec7/WED 10am: MSKCC’s Dr. Jedd Wolchok lecture at Wistar on “Combination Checkpoint Blockade"

Dec8/THU: 39th San Antonio Breast Cancer Symposium” http://tinyurl.com/zb5sopc
...Dr. Bruce Freimark(Dir.Res/Preclin.Oncology) poster: “PS-Targeting Enhances Anti-LAG3 in Murine Breast Cancer Tumors”

Dec12/MON??: FY'17Q2 (qe 10-31-16) Financials & Conf. Call - http://ir.peregrineinc.com/events.cfm

Dec11-15/Avid/Booth#209: IBC's Antibody Eng. & Therapeutics 2016”, SanDiego http://www.ibclifesciences.com/AntibodyEng/overview.xml

[cjgaddy]

Mem.Sloan’s Jedd.Wolchok Video/July2014: “Immunotherapy for Metastatic Melanoma, PD-1 Clinical Trials”… Dr. Wolchok (1:42), “We will not rest until every patient can have a durable response.” http://cyberspaceandtime.com/kvWeW8Zt0sU.video (1:49)

TOMORROW:
12-7-16/WED 10am: JEDD D. WOLCHOK, MD/PhD(Mem. Sloan Kettering)
Lecture: ”Combination Checkpoint Blockade" (free to public)
Location: The Wistar Institute, Philadelphia (Jedd D. Wolchock: Chief of Melanoma & Immunotherapeutics Service, MSKCC)
https://www.wistar.org/events/2016/12/combination-checkpoint-blockade
...We don’t know if Dr. Wolchok will mention Peregrine/Bavi in his talk (North40000/Eb0783/Wook will let us know!), but RECALL that on 11-14-16, Dr. Wolchok’s MSKCC Lab Team, jointly with PPHM Scientists, presented a poster at SITC’16 on Triple Combo Rad+Bavi+aPD1 vs. Melanoma:
...11-14-16/SITC’16: Dr. Jedd Wolchok states, “Based on these study results, we believe that the targeting of PS is having meaningful activity within the tumor microenvironment in the B16 melanoma model. It appears that this activity creates a more immune active environment in which other treatments, including radiation, are able to have a greater anti-tumor impact.”
#199/SITC’16/11-11-16(MSK+PPHM): Phosphatidylserine Targeting Antibody in Combination with Checkpoint Blockade & Tumor Radiation Therapy Promotes Anti-Cancer Activity in Mouse Melanoma” See: http://tinyurl.com/js3fca4

5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8

= = = = = = = = = = = = = = = =KNOWN DECEMBER:
Dec7/WED: WCLC’16 - IASLC’s 17th World Conf. on Lung Cancer, Vienna, Austria http://tinyurl.com/z8cq8vx
…2:30-3:45pm UTSW’s Dr. David Gerber to present addl. Biomarker data from Ph3.SUNRISE Trial: “A Pre-Treatment Serum Test Based on Complement & IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel”

Dec7/WED 10am: MSKCC’s Dr. Jedd Wolchok lecture at Wistar on “Combination Checkpoint Blockade"

Dec8/THU: 39th San Antonio Breast Cancer Symposium” http://tinyurl.com/zb5sopc
...Dr. Bruce Freimark(Dir.Res/Preclin.Oncology) poster: “PS-Targeting Enhances Anti-LAG3 in Murine Breast Cancer Tumors”

Dec12/MON/AfterMkt: FY'17Q2 (qe 10-31-16) Financials & Conf. Call - http://ir.peregrineinc.com/events.cfm

Dec11-15/Avid/Booth#209: IBC's Antibody Eng. & Therapeutics 2016”, SanDiego http://www.ibclifesciences.com/AntibodyEng/overview.xml

CONCLUSION SECTION FROM THE JOINT MSKCC/PPHM SITC’16 POSTER:




11-14-16/SITC'16: Dr. Taha Merghoub (Co-Dir., Ludwig Collaborative Lab at MSK): "We have noted that the combination of PS-targeting treatment and radiation, as well as triple combination of PS-targeting treatment, radiation and anti-PD-1, resulted in clear advantages in anti-tumor activity in the mouse B16 melanoma model. We believe that these findings suggest the potential benefit of combining these agents to improve the outcomes of patients with cancer. With this in mind, we think this research may play an important role in designing future clinical trials of PS-targeting agents in melanoma and other cancers."
http://tinyurl.com/js3fca4

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Oct9-11 2017: “EACR Conf. - Defense is the Best Attack: Immuno-Oncology Breakthroughs”, Barcelona
https://www.eacr.org/meeting/defence-is-the-best-attack-immuno-oncology-breakthroughs
EACR = Eur. Association for Cancer Research https://www.eacr.org
Keynote Speaker: Dr. Jedd Wolchok, MSKCC

[cjgaddy]

2-9-17/AACR Article: R.Birge+PPHM, “PS Sensing by TAM Receptors Regulates AKT-dependent Chemoresistance & PD-L1 Expression”. Lead author, Rutgers' Dr. Raymond Birge. Also, 2 co-authors from Advanced Proteome Therapeutics, in addition to PPHM scientists.

2-9-17/AACR: “Phosphatidylserine Sensing by TAM Receptors Regulates AKT-dependent Chemoresistance and PD-L1 Expression”
Rec. 10-27-16, rev. 12-30-16, Acc 1-13-17, PUB. 2-9-17
*RUTGERS: Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Sergei V Kotenko, Raymond B. Birge [Lead Author http://birgelab.org ]
*ADVANCED PROTEOME THERAPEUTICS: Allen Krantz, Andrzej Wilczynski http://advancedproteome.com
*BOSTON UNIV: Grzegorz Rymarczyk
*PEREGRINE: Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins
http://mcr.aacrjournals.org/content/early/2017/02/09/1541-7786.MCR-16-0350
https://www.ncbi.nlm.nih.gov/pubmed/28184013
ABSTRACT:
Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity. In the present study, we utilized TAM-IFNgammaR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express WT TAM receptors, and show that while each receptor can promote PS-mediated efferocytosis, AKT-mediated chemo-resistance, as well as up-regulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 [***] and Annexin V, demonstrating the existing of a PS/PS-Receptor (i.e. TAM-receptor) /PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1 based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to up-regulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on breast cancers cells.
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[***NOTE: Mab 11.31 is PGN632 (B2GPI-indep.), the Duke-PPHM-HIV candidate=11.31=AT005; also being studied by PPHM+LSU vs. Ocular Herpes (Acute HSV-1 Keratitis), see http://tinyurl.com/cax9a4p ]

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Interesting that one Birge/Rutgers Lab Member’s Theme/Mission is, “Regulation of Phosphatidylserine (PS) Externalization in the Tumor Micro-Environment; Role of PS as an Immunosuppressive Signal”. http://birgelab.org/lab.html

Raymond Birge, PhD - Univ. of Connecticut, Post-doc: Rockefeller Univ.
“Cancer Metastasis and Immune Evasion”
...Dr. Raymond Birge has authored ~85 scientific publications in molecular & cancer biology. http://www.ncbi.nlm.nih.gov/pubmed/?term=birge+rb
http://birgelab.org => http://birgelab.org/biography.html
“The Birge laboratory conducts basic science focused on the eradication of cancer.”


Ke Geng - BS: Zhengzhou Univ. Medical School
“Regulation of Phosphatidylserine (PS) Externalization in the Tumor Micro-Environment; Role of PS as an Immunosuppressive Signal”


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2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, ”Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9

11-9-15 SITC'15: New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w
...Also, collab. with Dr. Bernard Fox (Immunotherapist/Earle A. Chiles Res.Inst.) on new Immuno-Profiling Clinical Test (Opal 6-plex quantitative IF Assay), PPHM roundtable with Raymond Birge (Rutgers), Douglas Graham (Emory), Dmitry Gabrilovich (Wistar), Rolf Brekken (UTSW), Maria Karasarides (AstraZeneca) - ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.”

[biopharm]

2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, “Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9
..
....

Lots of good info CJ and the PS Targeting related royalties milestones etc etc from Oncologie Inc are on target, especially with Merck ties to Rutgers

I think some my have underestimated Dr Raymond Birge and Dr David Calianese with PS Targeting research

Looking at the research in 2017 / 2018 the same time the BOD shake up via John Springs Stafford there looks to be some new HIV info related to anti-PS

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Call for papers on Biology of Phosphatidylserine (PS): Basic Physiology and Implications in Immunology, Infectious disease, and Cancer

Edited by
Ray Birge, New Jersey Medical School, USA

David Calianese, New Jersey Medical School, USA

To maintain membrane potential and carry out the essential biochemical functions of living cells, the lipids in the biological membranes require asymmetric distribution across the lipid bilayer, whereby the phospholipids phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly maintained on the outer leaflet, while phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) are on the inner leaflet. While PS asymmetry (i.e., PS on the inner leaflet), is maintained under homeostatic conditions, this organization collapses under a variety of physiological and pathological conditions resulting in dramatic changes in the biochemical properties of the membrane. Most emblematically, the redistribution of PS to the external surface of the plasma membrane flags cells for their recognition, phagocytosis, and ultimate degradation by phagocytes (efferocytosis). However, this activity is not solely restricted to cells that undergo an apoptotic program. In fact, there are many instances (ie. during cellular stress or activation) where PS externalization occurs transiently and does not flag cells for engulfment by phagocytes, but regulates the activation status of the cell and various physiological functions.

Historically, investigation of disease biology, etiology and progression is aimed to identify genetic aberrations and/or useful protein biomarkers, whereas other macromolecules, notably phospholipids, are less uniformly appreciated. However, in recent years more evidence has been generated to suggest that PS dysregulation has profound immunological consequences in a variety of pathologies that include chronic inflammation, cancer, anti-phospholipid syndrome, and viral/protest infection and disease etiology. For example, it has been demonstrated that in many solid tumor types, PS externalization is constitutively exposed on cells that compose the tumor microenvironment, making PS a promising biomarker as well as a target for therapeutic intervention. Finally, exposure of PS on the outer surface of pathogens, from parasites, viruses, to bacterial species, is hijacked and used to gain entry to host cells as well as modulate immune responses in favor of disease progression.

This Thematic Series of Cell Communication and Signaling aims to address the biological functions of PS as well as its pathological role in various diseases. This issue will highlight recently published research as well as reviews that cover all facets of PS research.

Submission instructions

Before submitting your manuscript, please ensure you have carefully read the submission guidelines for Cell Communication and Signaling. The complete manuscript should be submitted through the journal submission system. To ensure that you submit to the correct thematic series please select the appropriate section in the drop-down menu upon submission. In addition, indicate within your cover letter that you wish your manuscript to be considered as part of the thematic series on series title. All submissions will undergo rigorous peer review, and accepted articles will be published within the journal as a collection.

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David Calianese
Researcher, Phd Candidate at Rutgers University - New Jersey Medical School
Newark, New Jersey
Research396

Summary
Since the fall of 2014, I have been pursuing a doctoral degree at Rutgers Graduate School of Biomedical Science in the field of Immuno-Oncology in the lab of Dr. Raymond Birge. My thesis work investigates the interaction of an anionic phospholipid, phosphatidylserine (PS), with the receptor family Tyro3, Axl, and Mertk (TAM) and its contribution to immune evasion in cancer. In addition to studying the biology behind this interaction I have been extensively involved in PS/TAM drug R&D ranging from monoclonal development/characterization to small molecule inhibitor studies. In January of 2017 I received a 2-year competitive predoctoral fellowship from the New Jersey Commission on Cancer Research (NJCCR) to engineer PS-targeting antibodies found in HIV-1 patients. The skills I have acquired through my lab experience are founded mainly in, but are not limited to, biochemistry and immunology. I have had seven years of total lab experience, while having five years in a management role conducting my own research while advising other students. I am also an active reviewer for the journal "Cell Communication and Signalling" (Nature Springer).

Prior to Matriculating at Rutgers, I worked as a research assistant under Dr. Yinsheng Wan, Associate Professor at Providence College where I studied the dysregulation of the PI3K/AKT pathways in a variety of cancer cell types. Moreover, in the spring of 2013, I worked in the lab of Dr. Wayne Bowen, Department Chair of Molecular Pharmacology, Physiology & Biotechnology at Brown University, under the direct supervision of Dr. Dioscaris Garcia and Dr. Harold Wanebo. In this position, I worked primarily with neuroblastoma and pancreatic cancer cells, and investigated the efficacy of a novel chemotherapeutic combination with C6-ceramide through in vitro experiments.

Honors & Awards
New Jersey Commission on Cancer Research Predoctoral Fellowship
New Jersey Commission on Cancer Research

January 2017

This is a competitive predoctoral fellowship that I received from the New Jersey Commission on Cancer Research (NJCCR) in January of 2017 for the project "Development of phosphatidylserine (PS) antibodies found in HIV positive patients".

The total amount of this award is $50,000, sponsoring two years of research towards a doctoral degree.