Replies to post #242093 on Avid Bioservices Inc (CDMO)

[cjgaddy]

My 1st-Cut Summary List of Peregrine Collabs & KOLs

PRECLIN:
UTSW/preclin: Dr. Philip Thorpe(Inventor/anti-PS/Bavi 1951-2013)=> Dr. Rolf Brekken http://www.utsouthwestern.edu/labs/brekken
Sloan-Kettering (Dr. Jedd Wolchok Lab): http://tinyurl.com/o3k9ux8
Duke (Dr. Herbert K. Lyerly): http://tinyurl.com/pbof95w
UC/Irvine (Dr. Christopher C.W. Hughes): http://tinyurl.com/omqj5m3
Providence CC/Opal 6-plex assay (Dr. Bernard A. Fox): http://tinyurl.com/ojrpvqy
Mayo/Ocular(Dr. Jose S. Pulido) http://tinyurl.com/qhdmsa5
Tulane/Ocular(Dr. Shusheng Wang) http://tinyurl.com/qhdmsa5

CLINICAL:
AstraZeneca (Dr. Robert Iannone Head/I-O, Maria Karasarides Sr.Dir/I-O): http://tinyurl.com/q79bkam
UTSW (Dr. David Gerber, Dr. Adam Yopp): http://tinyurl.com/nv4jloo & http://tinyurl.com/opkh5qy
Moffitt (Dr. Scott Antonia): http://tinyurl.com/p9eduac & http://tinyurl.com/qxu4w2x

IST's:
UTSW - Melanoma (Dr. Arthur Frankel): http://www.clinicaltrials.gov/ct2/show/NCT01984255
UTSW - Rectal (Dr. Jeffrey Meyer): http://www.clinicaltrials.gov/ct2/show/NCT01634685
UNC – NSCLC (Dr. Juneko Grilley-Olson): http://clinicaltrials.gov/ct2/show/NCT01323062
UNIV-ARIZ – Breast (Dr. Alison Stopeck) http://clinicaltrials.gov/ct2/show/NCT01288261
UTSW – Liver (Dr. Adam Yopp) http://www.clinicaltrials.gov/ct2/show/NCT01272791

SAB: http://www.peregrineinc.com/about-us/medical-and-scientific-advisors.html
Scott J. Antonia, M.D., Ph.D. - H. Lee Moffitt CC
Rolf Brekken, Ph.D. - UT Southwestern MC
David Carbone, M.D., Ph.D. - Ohio State Univ., President/IASLC
Bruce Chabner, M.D. - Mass. General Hosp., Harvard Medical School
Harold F. Dvorak, M.D. - Beth Israel Deaconess, Harvard Medical School
Dmitry I. Gabrilovich, M.D., Ph.D. - The Wistar Institute
Christopher C. W. Hughes, Ph.D. - Univ. of California/Irvine
Hakan Mellstedt, M.D., Ph.D. - Karolinska Institute, Sweden
Alan J. Schroit, Ph.D. - M.D. Anderson

SPEAKERS AT PPHM's 11-6-15 SITC'15 I-O Roundtable: http://tinyurl.com/pbof95w
(in addition to SAB'ers Dmitry Gabrilovich, Rolf Brekken, and AZN's Maria Karasarides)
Rutgers (Dr. Raymond Birge) http://birgelab.org
Emory (Dr. Douglas Graham) http://tinyurl.com/pugjnbt

SPEAKERS AT PPHM's 5-31-15 ASCO’15 I-O Roundtable: http://tinyurl.com/qxu4w2x
(in addition to SAB'ers Scott Antonia, Dmitry Gabrilovich, Rolf Brekken)
Loxo Oncology - BOD (Dr. Lori Kunkel) http://www.loxooncology.com
Indiana Univ. (Dr. Kathy D. Miller) http://www.bcrfcure.org/researchers/kathy-d-miller
Sloan-Kettering (Dr. Dmitriy Zamarin) https://www.mskcc.org/research-areas/labs/members/dmitriy-zamarin
Sloan-Kettering (Dr. Matthew D. Hellman) http://www.mskcc.org/cancer-care/doctors/matthew-hellmann
Sloan-Kettering (Dr. Alexander M. Lesokhin) http://www.mskcc.org/research-areas/labs/members/alexander-lesokhin-01

[cjgaddy]

Fri/12-11-15: Freimark/Hutchins Poster at Annual SanAntonio-Breast-Cancer-Symposium

Dec8-12 2015: 38th 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 and treatment our program continues to present essential up-to-the minute information combined with engrossing discussion for basic, translational and clinical cancer research professionals.
At SABCS'14, there were 7,362 Symposium attendees + 206 Media + 345 Exhibitors, Non-Exhibiting Sponsors & their Support Staff = 7,913 total attendance. More than 53% came from 94 countries outside the USA”
http://www.sabcs.org
http://www.sabcs.org/Program/Poster-Sessions/Poster-Session-4
12-11-15 7:30–9:00am Poster Session
TRACK: Tumor Cell & Molecular Biology: Immunology & Preclinical Immunotherapy
#P4-04-03 “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Immune Checkpoint Inhibitor PD-1/PD-L1 Therapy in Murine Breast Tumors”
M.Gray, J.Gong, V.Nguyen, Jeff Hutchins, Bruce Freimark - Peregrine Pharmaceuticals

= = = = = = = = =KNOWN UPCOMINGS:
Dec7-10/Avid/Booth307: IBC's Antibody Eng. & Therapeutics, SanDiego http://www.ibclifesciences.com/AntibodyEng

Dec10 4:30pmET(1:30pmPT): FY'16Q2 (qe 10-31-15) Financials & Conf. Call http://ir.peregrineinc.com/events.cfm

Dec11 7:30-9am: 38th Annual San Antonio Breast Cancer Symposium http://tinyurl.com/hyl8sqx
...Poster #P4-04-03 Freimark/Hutchins: “Targeting of PS by Mabs Augments the Activity of Immune Checkpoint Inhibitor PD-1/PD-L1 Therapy in Murine Breast Tumors”

Dec16: Roth Capital Partners' Immuno-Oncology Corp. Access Day, NYC http://tinyurl.com/p8ykuu7 (PPHM = 1 of 16 participating companies)

Mar6-11 2016: CHI’s 23rd Molecular Med TRI-CON 2016, SanFran http://www.triconference.com (Speaker: Dr. Jeff Hutchins, VP/Preclin.Res.)

~Mar10: FY'16Q3 (qe 1-31-16) Financials & Conf. Call http://ir.peregrineinc.com/events.cfm

Mar15-17 2016: Immune Checkpoint Inhibitors Conf., Boston http://immune-checkpoint.com (Peregrine is 1 of 4 Corp. Sponsors)

[cjgaddy]

Bruce Freimark (Dir/PreClin-Oncology) speaking 1-26-16 at GTCbio's Novel-Immunotherapeutics-Summit, SanDiego

Jan25-26 2016: “GTCbio's Novel Immunotherapeutics Summit”, San Diego
https://www.gtcbio.com/conferences/immunotherapeutics-summit-overview
GTC = Global Technology Community https://www.gtcbio.com/about-us
4 Sub-Conferences, including: 8TH IMMUNOTHERAPEUTICS & IMMUNOMONITORING
1-26-15: SESSION: ”Combinatorial Immunotherapies” - Moderator: Bruce Freimark, Peregrine Pharm.
4 Speakers:
*9:35am “DNA Vaccines with T-Cell Checkpoint Blockade”, Douglas McNeel, UNIV./WISCONSIN
*10:00am “Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Targeted Therapy & Immune Checkpoint Inhibitors by Reducing Immunosuppressive Cells in the Tumor Microenvironment”, Bruce Freimark (Res.Dir./Preclin.Oncology), PEREGRINE PHARMACEUTICALS
Abstract: The underlying cause for the failure of immune checkpoint blockade is persistent, multifocal immune suppression in the tumor microenvironment. This is due to the absence of pre-existing antitumor Teff because of the action of immune checkpoints that induce immunosuppressive cytokines and recruit tumor infiltrating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and M2 macrophages. Phosphatidylserine (PS) is segregated to the inner leaflet of the plasma membrane but becomes externalized to the outer leaflet in tumor cells where it contributes as an upstream checkpoint inhibitor to an immunosuppressive environment. Antibody blockade of PS reprograms the immune cells in the tumor microenvironment to support immune activation. Antibody-mediated PS blockade reduces the levels of MDSCs, TGF-beta, and IL-10 and increases the levels of TNF-alpha and IL-12. PS blockade also re-polarizes tumor-associated M2 macrophages to a M1 phenotype which promotes the maturation of dendritic cells and induces of adaptive T-cell responses. PS targeting antibodies enhance the anti-tumor activity of anti-CTLA-4 and anti-PD-1 antibodies in models of melanoma and breast cancer and correlates with an increase in the infiltration of activated T cells and the induction of adaptive immunity. In summary, PS blockade in combination with targeted therapy and other immune checkpoint inhibitors promotes a localized, anti-tumor response and represents a promising strategy to enhance cancer immunotherapy.
*10:25am “Cancer Vaccines in the Era of Checkpoint Blockade”, Willem Overwijk, MD.ANDERSON
*11:20am “Myeloid-Derived IL-10 & PD-1 Create a Vicious Immune...”, Keith Knutson, MAYO CLINIC



= = = = = = = = = = =OTHER KNOWN UPCOMINGS (2016):
Jan26: “GTCbio's Novel Immunotherapeutics Summit”, San Diego http://tinyurl.com/z3dyful
...10am, Dr. Bruce Freimark(ResDir./Preclin.Oncology): “Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Targeted Therapy & Immune Checkpoint Inhibitors by Reducing Immunosuppressive Cells in the Tumor Microenvironment”

Jan26-28/Avid/Booth20: CASSS' 20th Symposium on the Interface of Reg.&Anal. Sciences for Biotech Health Products, WashDC http://www.casss.org/?WCBP1600

Mar6-11: CHI’s 23rd Molecular Med TRI-CON 2016, SanFran http://www.triconference.com (Speaker: Dr. Jeff Hutchins, VP/Preclin.Res.)

~Mar10: FY'16Q3 (qe 1-31-16) Financials & Conf. Call http://ir.peregrineinc.com/events.cfm

Mar14-17/Avid/Booth712: IBC's BioProcess Intl. West, Oakland http://www.ibclifesciences.com/BPIWest/overview.xml

Mar15-17: Immune Checkpoint Inhibitors Conf., Boston http://immune-checkpoint.com (Peregrine is 1 of 4 Corp. Sponsors; Speaker: Dr. Jeff Hutchins, VP/Preclin.Res.)

Jun6-9/Avid/Booth5562: BIO Intl. Convention, SanFran http://convention.bio.org

= = = = = = = = = =PREVIOUS BAVI MOA PRESENTATIONS:
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.”
BAVI MOA 8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow http://tinyurl.com/qz64pzg
…“Expansion & Activation of T Cells via the Targeting of the Immunosuppressive Ligand PS: Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy”

5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x

BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7

BAVI MOA 2-9-15: PPHM/ResDir. Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6

BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs

BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h

[cjgaddy]

Rutgers' Dr. Raymond Birge, “PS: a Global Immunosuppressive Signal...”. Spoke at Peregrine's 11-2015 “Sci. Session” at SITC'15/Maryland; will be the chair in June'16 of the ICDS'16 session where Dr. Rolf Brekken (PPHM SAB) is speaking; and now also speaking in late June'16 at ICHC'16/Istanbul on, “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”… (Rutgers Univ. http://birgelab.org “The Birge laboratory conducts basic science focussed on the eradication of cancer.”)

June19-22 2016: “15th Intl. Congress of Histochemistry & Cytochemistry - from Molecules to Diseases”, Istanbul Turkey
“The main goal of ICHC 2016 is to bring the worldwide histochemists together and provide an environment for close cooperation, exchange of information, and collaborations.”
http://www.ichc2016.com
INVITED SPEAKER – Session: “Cellular Aging & Cell Death”
Dr. Raymond Birge (Rutgers Univ. http://birgelab.org ), “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”

=======DR. RAY BIRGE (RUTGERS):
June2-4 2016: ICDS 2016: Translational Implications in Cell Death", Cork Ireland http://tinyurl.com/h2gvyld
...Dr. Rolf Brekken (USA, UTSE, PPHM SAB): “Blockade of PS & Immune Activation in Cancer” (Chair: Dr. Raymond Birge/Rutgers – see http://tinyurl.com/oks5uo6 )

Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
...Join Peregrine for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
- - - - - - - -
SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly, Duke Univ.** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”

[cjgaddy]

I do believe Dr. Raymond Birge is ALL-IN! Great find, Biopharm on Dr. Birge's Youtube statement (SEE BELOW) that perfect parallels Bavi's MOA… More later – gotta run...

= = = = = =
Rutgers' Dr. Raymond Birge, “PS: a Global Immunosuppressive Signal...”. Spoke at Peregrine's 11-2015 “Sci. Session” at SITC'15/Maryland; will be the chair in June'16 of the ICDS'16/Ireland session where Dr. Rolf Brekken (PPHM SAB) is speaking; and now also speaking in late June'16 at ICHC'16/Istanbul on, “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”… (Rutgers Univ. http://birgelab.org “The Birge laboratory conducts basic science focussed on the eradication of cancer.”)

June19-22 2016: “15th Intl. Congress of Histochemistry & Cytochemistry - from Molecules to Diseases”, Istanbul Turkey
“The main goal of ICHC 2016 is to bring the worldwide histochemists together and provide an environment for close cooperation, exchange of information, and collaborations.”
http://www.ichc2016.com
INVITED SPEAKER – Session: “Cellular Aging & Cell Death”
Dr. Raymond Birge (Rutgers Univ. http://birgelab.org ), “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”

= = = = = = = = = = = = = = = = = = =
3-1-14/Youtube: “Cancer Research” - Raymond Birge Laboratory, Rutgers http://birgelab.org

Dr. Birge/2:54: "The immune system is very complex and if it can recognize tumors as being foreign to the body, then it can reactivate & eliminate these tumors to treat as a chronic disease, or in some cases eliminate the tumors. One of the projects that our lab is interested in is how to reactivate the immune system toward particular cancers, and we believe that the type of cell death that cancer cells undergo will determine whether or not they'll be an immune reaction against the cancer. If cells die, through a process called apoptosis, in a certain way, they can reactivate / activate the immune system and give a durable, anti-tumor response. The problem that we're trying to understand is how the tumor cells evade the immune system and therefore block these immune-suppressing signals to reactivate the immune system against cancer..."


=======DR. RAY BIRGE (RUTGERS) & PEREGRINE:
June2-4 2016: ICDS 2016: Translational Implications in Cell Death", Cork Ireland http://tinyurl.com/h2gvyld
...Dr. Rolf Brekken (USA, UTSE, PPHM SAB): “Blockade of PS & Immune Activation in Cancer” (Chair: Dr. Raymond Birge/Rutgers – see http://tinyurl.com/oks5uo6 )

Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
...Join Peregrine for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
- - - - - - - -
SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly, Duke Univ.** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”

[cjgaddy]

Rutgers' Dr. Raymond Birge's 3-1-14 Youtube on Cell-Death/Apoptosis & “blocking these immune-suppressing signals to reactivate the immune system against cancer…".

Dr. Birge spoke at Peregrine's 11-2015 “Sci. Session” at SITC'15/Maryland; will be the chair in June'16 of the ICDS'16/Ireland session where Dr. Rolf Brekken (PPHM SAB) is speaking on “Blockade of PS & Immune Activation in Cancer”; and now also speaking in late June'16 at ICHC'16/Istanbul on, “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”.
Rutgers Univ: http://birgelab.org “The Birge laboratory conducts basic science focused on the eradication of cancer.”

3-1-14/Youtube: “Cancer Research” - Dr. Raymond Birge Laboratory, Rutgers http://birgelab.org

Dr. Birge/2:54: "The immune system is very complex and if it can recognize tumors as being foreign to the body, then it can reactivate & eliminate these tumors to treat as a chronic disease, or in some cases eliminate the tumors. One of the projects that our lab is interested in is how to reactivate the immune system toward particular cancers, and we believe that the type of cell death that cancer cells undergo will determine whether or not they'll be an immune reaction against the cancer. If cells die, through a process called apoptosis, in a certain way, they can reactivate / activate the immune system and give a durable, anti-tumor response. The problem that we're trying to understand is how the tumor cells evade the immune system and therefore block these immune-suppressing signals to reactivate the immune system against cancer..."


DR. BIRGE, CLEARLY IN STEP WITH DR. THORPE, DR. BREKKEN, AND PEREGRINE PHARMACEUTICALS...

5-1-12/NYAS: Dr. Philip Thorpe (UTSW, RIP/1951-2013) on Bavi MOA: http://tinyurl.com/9792gl5
“As a 2nd mechanism, bavituximab can overcome the immunosuppressive processes observed with cells that externalize PS. In tumors the expression of PS on cell surfaces keeps macrophages in their M2 state, an activation state that suppresses inflammation and supports angiogenesis. It also prevents myeloid-derived suppressor cells (MDSCs) from differentiating into macrophages and dendritic cells (DCs). In addition, PS inhibits the maturation of DCs, which prevents the presentation of antigens to T cells. Bavituximab repolarizes macrophages to their M1 state, which allows them to kill cells that express PS, including the tumor vascular endothelium. It also leads to differentiation of the MDSCs and prompts DCs to mature and to present tumor antigens to T cells.”

5-28-14/NYAS: Dr. Rolf Brekken (UTSW) http://tinyurl.com/lq9stnk
“Phosphatidylserine (PS) is a potent immunosuppressive lipid typically segregated to the inner leaflet of the plasma membrane. PS is externalized on tumor vasculature, tumor-derived exosomes, and tumor cells in the tumor microenvironment and externalization is enhanced by therapy. Externalized PS interacts with immune cells where it actively promotes expansion of myeloid derived suppressor cells (MDSCs) and M2-like tumor associated macrophages (TAMs), which drive immunosuppression and tumor progression. In preclinical studies, treatment of tumor-bearing mice with murine-versions of bavituximab significantly depleted M2-likeTAMs & MDSCs and increased the presence of M1-like TAMs and mature dendritic cells. In addition, PS blockade shifted the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. Furthermore, in the immune-competent tumor models combination of standard of care therapy with PS blockade induced potent durable tumor-specific T-cell immunity and significantly improved tumor free long-term survival. These data suggest that externalized PS defines a global immune checkpoint in tumors and support that antibody-mediated PS blockade can reverse PS-mediated immune checkpoint suppression, revitalize innate and the adaptive immunity, and promote therapeutically effective anti-tumor immunity.”

1-16-16/PR: About Bavituximab: A Targeted Investigational Immunotherapy”
“Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine's PS targeted inhibitor, bavituximab, is thought to reverse the immunosuppressive environment that many tumors establish in order to proliferate and spread, while also fighting cancer by activating immune cells that target and fight cancer.”
“Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS and, in turn, is believed to remove this immunosuppressive signal and send an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=949704

====================DR. RAY BIRGE (RUTGERS) & PEREGRINE:
June2-4 2016: ICDS 2016: Translational Implications in Cell Death", Cork Ireland http://tinyurl.com/h2gvyld
...Dr. Rolf Brekken (USA, UTSE, PPHM SAB): “Blockade of PS & Immune Activation in Cancer” (Chair: Dr. Raymond Birge/Rutgers – see http://tinyurl.com/oks5uo6 )

June19-22 2016: “15th Intl. Congress of Histochemistry & Cytochemistry - from Molecules to Diseases”, Istanbul Turkey
“The main goal of ICHC 2016 is to bring the worldwide histochemists together and provide an environment for close cooperation, exchange of information, and collaborations.”
http://www.ichc2016.com
INVITED SPEAKER – Session: “Cellular Aging & Cell Death”
Dr. Raymond Birge (Rutgers Univ. http://birgelab.org ), “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”

Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
...Join Peregrine for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
- - - - - - - -
SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly, Duke Univ.** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”

[cjgaddy]

Immunotherapy World/WashDC(Dr.Hutchins) delayed by 1day =>TUE.



PPHM's Jeff Hutchins(VP/PreClinRes) speaking 1-25-16 (<=DELAYED 1 DAY!) at Immunotherapy World Conf. (WashDC)
“750 deal-makers will gather to discuss the direction, future and value of cell, gene and immunotherapy portfolios.”

Jan25-27 2016: “Phacilitate's Immunotherapy World Conf.”, WashDC
http://www.immunotherapyforum.com
“After years of posting impressive clinical results and pushing analyst projections to greater and greater heights, immuno-oncology has solidified its status as the most exciting development in cancer treatment for a long time. Now that checkpoint inhibitors have uncloaked cancer cells, drug developers are investigating dozens of immune drug cocktails (everything from CAR-T to antibodies, vaccines and other cellular therapies) to find well-tolerated treatments which could become the first-in-line to fight cancer in patients. We have all heard of the stunning breakthroughs at ASCO'15. BMS’ Opdivo + Yervoy study which lead to a 58% shrinkage of tumors and a PFS superiority of 8.6mos. against monotherapies in patients with melanoma. AstraZeneca’s own PD-L1 (MEDI4736/durvalumab) [see 10-15-15 AZN/PPHM Collab. Expansion: http://tinyurl.com/q79bkam ] and CTLA-4 (Tremelimumab) inhibitor combination, which demonstrated an ORR of 27% in the treatment of NSCLC… On Jan25-27 2016, 750 deal-makers will gather in the Grand Hyatt Hotel to discuss the direction, future and value of cell, gene and immunotherapy portfolios.”
CONF. DELAYED by ONE DAY DUE TO STORM:
http://www.immunotherapyforum.com/files/new_immunotherapy_agenda.pdf
---------
Jan25(Day1): Focus Session1, “Cellular Cancer Immunotherapy: Optimizing Combination Therapy Development Strategy”
3:15pm: Chair's intro, David Lebwohl, NOVARTIS
3:20: Michael Hanna, VACCINOGEN, “The Provocative Issues of Tumor Heterogeneity on Active Specific Immunotherapy...”
3:35: Laura Benjamin, ELI LILLY, “Challenges/Opportunities for Translational Science to Guide Angiogenesis/Combos w/Immunotherapy”
3:50: Taylor Schreiber, HEAT BIOLOGICS, “Dual-Acting Immunotherapy with ComPACT - Vaccination & Co-Stimulation...”
-------
1-25-16 4:05-4:20pm: Jeff T. Hutchins (PEREGRINE'S VP/PreClinRes), “Combination Immunotherapies - Opening the Gate: Increasing Tumor Infiltrating Activated T-cells to Optimize and Expand the Benefits of Immune Checkpoint Therapies”
* Analyzing complimentary mechanisms in therapeutics and building solid partnerships
* Utilizing scientifically-driven data to build a product value story
* Demonstrating how a product fits within a treatment in combination(s) and against competitive therapies
-------
4:20pm: Robert Preti, PCT(CALADRIUS), “What Does Commercialization Look Like?”

- - - - - - - - - - - - - - - -From PPHM's 1-20-16 PR: http://tinyurl.com/z65avfw
“In his talk, Dr. Hutchins will discuss strategies for expanding the therapeutic benefit seen with immuno-oncology monotherapies to a broader range of patients using combination treatment approaches. Specifically, he will highlight the strategy of leveraging treatments capable of increasing the number & activity of T-cells in the tumor microenvironment to optimize the therapeutic benefit of immune checkpoint inhibitors such as anti-PD-1/anti-PDL-1 agents. Dr. Hutchins will draw on the company's experience in working with preclinical equivalents of bavituximab, Peregrine's lead investigational phosphatidylserine (PS)-targeting immunotherapy candidate. PS-targeting antibodies have been shown to shift the immunosuppressive functions of immune cells in tumors, resulting in anti-tumor immune responses. Peregrine has generated results from multiple preclinical & clinical-translational studies demonstrating enhanced anti-tumor activity and immune activation when combining equivalent PS-targeting antibodies with conventional chemotherapy or checkpoint inhibitors such as anti-PD-1 agents.”

= = = = = = = = = = = = = = = = = = = =
Bruce Freimark (Dir/PreClin-Oncology) speaking 1-26-16 at GTCbio's Novel-Immunotherapeutics-Summit, SanDiego

Jan25-26 2016: “GTCbio's Novel Immunotherapeutics Summit”, San Diego
https://www.gtcbio.com/conferences/immunotherapeutics-summit-overview
GTC = Global Technology Community https://www.gtcbio.com/about-us
4 Sub-Conferences, including: 8TH IMMUNOTHERAPEUTICS & IMMUNOMONITORING
1-26-15: SESSION: ”Combinatorial Immunotherapies” - Moderator: Bruce Freimark, Peregrine Pharm.
4 Speakers:
*9:35am “DNA Vaccines with T-Cell Checkpoint Blockade”, Douglas McNeel, UNIV./WISCONSIN
*10:00am “Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Targeted Therapy & Immune Checkpoint Inhibitors by Reducing Immunosuppressive Cells in the Tumor Microenvironment”, Bruce Freimark (Res.Dir./Preclin.Oncology), PEREGRINE PHARMACEUTICALS
Abstract: The underlying cause for the failure of immune checkpoint blockade is persistent, multifocal immune suppression in the tumor microenvironment. This is due to the absence of pre-existing antitumor Teff because of the action of immune checkpoints that induce immunosuppressive cytokines and recruit tumor infiltrating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and M2 macrophages. Phosphatidylserine (PS) is segregated to the inner leaflet of the plasma membrane but becomes externalized to the outer leaflet in tumor cells where it contributes as an upstream checkpoint inhibitor to an immunosuppressive environment. Antibody blockade of PS reprograms the immune cells in the tumor microenvironment to support immune activation. Antibody-mediated PS blockade reduces the levels of MDSCs, TGF-beta, and IL-10 and increases the levels of TNF-alpha and IL-12. PS blockade also re-polarizes tumor-associated M2 macrophages to a M1 phenotype which promotes the maturation of dendritic cells and induces of adaptive T-cell responses. PS targeting antibodies enhance the anti-tumor activity of anti-CTLA-4 and anti-PD-1 antibodies in models of melanoma and breast cancer and correlates with an increase in the infiltration of activated T cells and the induction of adaptive immunity. In summary, PS blockade in combination with targeted therapy and other immune checkpoint inhibitors promotes a localized, anti-tumor response and represents a promising strategy to enhance cancer immunotherapy.
*10:25am “Cancer Vaccines in the Era of Checkpoint Blockade”, Willem Overwijk, MD.ANDERSON
*11:20am “Myeloid-Derived IL-10 & PD-1 Create a Vicious Immune...”, Keith Knutson, MAYO CLINIC

- - - - - - - - - - - - - - - -From PPHM's 1-20-16 PR: http://tinyurl.com/z65avfw
“Dr. Freimark will highlight data showing that blocking PS signaling in combination with immune checkpoint inhibitors promotes a localized, anti-tumor response. He will share research findings demonstrating that PS-targeting antibodies enhance the anti-tumor activity of anti-CTLA-4 & anti-PD-1 antibodies in models of melanoma & breast cancer and correlate with an increase in the infiltration of activated T-cells and the induction of adaptive immunity. Both [Dr.Hutchins/1-25-16 & Dr.Freimank/1-26-16] presentations will also highlight key recent research findings showing that PS-signaling pathway inhibitors demonstrate multiple signs of immune activation in low or negative PD-L1 tumors. This suggests that PS-targeting antibodies have the potential to show a clinical benefit in patients with low PD-L1 levels and who do not generally benefit from checkpoint treatment alone. The potential for bavituximab to improve the clinical outcome of checkpoint inhibitors will be evaluated as part of Peregrine's ongoing clinical research collaboration with AstraZeneca. To this end, a global Phase II study of bavituximab in combination with AstraZeneca's durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with previously treated squamous or non-squamous NSCLC is expected to begin during Q1/2016.”

= = = = = = = = = =
Jan26-28 2016: “20th Symposium on the Interface of Regulatory & Analytical Sciences for Biotechnology Health Products”, WashDC
http://www.casss.org/?WCBP1600
CASSS = Calif. Separation Science Society (“the detailed study & controlled separation of mixtures - also referred to as “chromatography”. Major advances in separation science have enabled biologists, chemists, pharmacists and environmentalists to make breakthroughs of their own. Genomics, drug discovery, DNA fingerprinting, and ultra-trace residue analysis, for instance, would not be possible without recourse to the findings generated by separation science.
Visit Avid at table #20

[cjgaddy]

2-26-16/Dr.Raymond.Birge article: “Phosphatidylserine is a Global Immunosuppressive Signal...” - Cell Death & Differentiation, online pub. 2-26-16.

2-26-16: “Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer”
'Cell Death & Differentiation Jrnl' online pub. 2-26-16 (rec.10-31-15; acc.1-7-16)
Raymond Birge 1; S Boeltz 2; S Kumar 1; J Carlson 3; J Wanderley 4; D Calianese 1; M Barcinski5; Rolf Brekken 6,7; Xianming Huang 6,7; Jeff Hutchins 3; Bruce Freimark 3; C Empig 3; J Mercer 8; A J Schroit 9; G Schett 2; Martin Herrmann 2
1. Dept of Microbiology, Biochemistry & Molecular Genetics, CC, Rutgers NJ Medical School, Newark, NJ
2. Dept of Internal Medicine, Rheumatology & Immunology, Friedrich-Alexander-Univ., Erlangen, Germany
3. Peregrine Pharma., Tustin, CA
4. Universidade Federal do Rio de Janeiro, Brazil
5. Lab de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
6. Div. of Surgical Oncology, Hamon Ctr for Therapeutic Oncology Res., UTSW-MC/Dallas
7. Dept of Pharmacology, UTSW-MC/Dallas
8. Medical Research Council Lab for Molecular Cell Biology, Univ. College London
9. Simmons Cancer Center & Dept of Immunology, UTSW-MC/Dallas
ABSTRACT
Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer & infectious disease therapeutics.
FULL ARTICLE: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd201611a.html


= = = = = = = = = =UPCOMING:
June2-4: ICDS 2016: Translational Implications in Cell Death", Cork Ireland http://tinyurl.com/h2gvyld
...Dr. Rolf Brekken (USA, UTSE, PPHM SAB): ”Blockade of PS & Immune Activation in Cancer” (Chair: Dr. Raymond Birge/Rutgers – see http://tinyurl.com/j3whbx3 )

Jun19-22: “ICDS'16 - From Molecules To Diseases”, Istanbul Turkey http://tinyurl.com/h4zjvo4
….Rutgers' Dr. Raymond Birge ( http://birgelab.org ) ”Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer” - see http://tinyurl.com/j3whbx3

= = = = = = = = = = = = =PREV:
June2015: DR RAYMOND BIRGE & Dr. Xianming Huang (Dr.Rolf.Brekken-Lab) at Gordon Res. Conference in Maine on 6-15-15 – speaking next to each other in “Consequences of Lipid Alterations” Session. Peregrine was the only corp. contributor to this conference, specified as, “In Memory of Dr. Philip E. Thorpe.”...

June 14-19, 2015: “Apoptotic Cell Recognition & Clearance”, Gordon Research Conference, Biddeford, ME
Chair: David S. Ucker, Vice Chairs: Peter Henson & Kirsten Lauber
http://www.grc.org/programs.aspx?id=13127
”Moreover, apoptotic cells are potently immunosuppressive, and their clearance occurs in the absence of inflammation. Recognition & inflammatory modulation represent key elements of an innate immunity that discriminates live from effete cells.”
**The only Corp. Sponsor: PEREGRINE PHARM, “Generous financial support from Peregrine Pharmaceuticals is in memory of Dr. Philip E. Thorpe.”
- - - - - - - -
SESSION: “Consequences of Lipid Alterations for Apoptotic Cell Clearance
Discussion Leader: Christopher Gregory (Univ. of Edinburgh, UK)
7:30pm: Ian Dransfield (Univ. of Edinburgh, UK), “Protein S Binding to Apoptotic Cells...”
8:10pm: Dr. Raymond Birge (Rutgers NJMS), “Apoptotic Cell Recognition Receptors, Tyro3/Axl/Mer...”
8:50pm: Dr. Xianming Huang** (UTSW-MC/Dallas, Brekken Lab), “PS-Targeting Antibodies Overcome Tumor Immunosuppression and Synergize with Immune Checkpoint Blockade"
**Dr. Xianming Huang: formerly in Dr. Philip Thorpe's Lab (RIP, Dr. Thorpe, 1951-2013 http://tinyurl.com/l9gqmt5 ), now in Dr. Rolf Brekken's (PPHM SAB) Lab.
http://www.utsouthwestern.edu/labs/brekken/

= = = = = = = = = = = = = =DR. BIRGE:
...Dr. Raymond Birge has authored ~85 scientific publications in molecular & cancer biology. http://www.ncbi.nlm.nih.gov/pubmed/?term=birge+rb
“The Birge laboratory conducts basic science focused on the eradication of cancer.”
http://birgelab.org => http://birgelab.org/biography.html

====================DR. RAY BIRGE (RUTGERS) & PEREGRINE:
June19-22 2016: “15th Intl. Congress of Histochemistry & Cytochemistry - from Molecules to Diseases”, Istanbul Turkey
“The main goal of ICHC 2016 is to bring the worldwide histochemists together and provide an environment for close cooperation, exchange of information, and collaborations.”
http://www.ichc2016.com
INVITED SPEAKER – Session: “Cellular Aging & Cell Death”
Dr. Raymond Birge (Rutgers Univ. http://birgelab.org ), “Phosphatidylserine is a Global Immunosuppressive Signal in Cell Death & Cancer”

Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
...Join Peregrine for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
- - - - - - - -
SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly, Duke Univ.** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”

Oct29 2015: “John-Hopkins Molecular Microbiology & Immunology Seminar”, Baltimore http://tinyurl.com/oks5uo6
...12-1:00pm: "Phosphatidylserine is a Global Immune Checkpoint In Cancer"
Raymond Birge, PhD, Vice Chair, Professor, Dept of Molecular, Biochemistry & Molecular Genetics, Rutgers Univ., Newark, NJ


= = = = = = = = = = = = = = = = = = = = = = = = = =
DR. BIRGE, CLEARLY IN STEP WITH DR. THORPE, DR. BREKKEN, AND PEREGRINE PHARMACEUTICALS...

5-1-12/NYAS: Dr. Philip Thorpe (UTSW, RIP/1951-2013) on Bavi MOA: http://tinyurl.com/9792gl5
“As a 2nd mechanism, bavituximab can overcome the immunosuppressive processes observed with cells that externalize PS. In tumors the expression of PS on cell surfaces keeps macrophages in their M2 state, an activation state that suppresses inflammation and supports angiogenesis. It also prevents myeloid-derived suppressor cells (MDSCs) from differentiating into macrophages and dendritic cells (DCs). In addition, PS inhibits the maturation of DCs, which prevents the presentation of antigens to T cells. Bavituximab repolarizes macrophages to their M1 state, which allows them to kill cells that express PS, including the tumor vascular endothelium. It also leads to differentiation of the MDSCs and prompts DCs to mature and to present tumor antigens to T cells.”

5-28-14/NYAS: Dr. Rolf Brekken (UTSW) http://tinyurl.com/lq9stnk
“Phosphatidylserine (PS) is a potent immunosuppressive lipid typically segregated to the inner leaflet of the plasma membrane. PS is externalized on tumor vasculature, tumor-derived exosomes, and tumor cells in the tumor microenvironment and externalization is enhanced by therapy. Externalized PS interacts with immune cells where it actively promotes expansion of myeloid derived suppressor cells (MDSCs) and M2-like tumor associated macrophages (TAMs), which drive immunosuppression and tumor progression. In preclinical studies, treatment of tumor-bearing mice with murine-versions of bavituximab significantly depleted M2-likeTAMs & MDSCs and increased the presence of M1-like TAMs and mature dendritic cells. In addition, PS blockade shifted the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. Furthermore, in the immune-competent tumor models combination of standard of care therapy with PS blockade induced potent durable tumor-specific T-cell immunity and significantly improved tumor free long-term survival. These data suggest that externalized PS defines a global immune checkpoint in tumors and support that antibody-mediated PS blockade can reverse PS-mediated immune checkpoint suppression, revitalize innate and the adaptive immunity, and promote therapeutically effective anti-tumor immunity.”

1-16-16/PR: About Bavituximab: A Targeted Investigational Immunotherapy”
“Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine's PS targeted inhibitor, bavituximab, is thought to reverse the immunosuppressive environment that many tumors establish in order to proliferate and spread, while also fighting cancer by activating immune cells that target and fight cancer.”
“Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS and, in turn, is believed to remove this immunosuppressive signal and send an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=949704

3-1-2014/Youtube: “Cancer Research” - Dr. Raymond Birge Laboratory, Rutgers http://birgelab.org
http://www.youtube.com/watch?v=HdacTc_I7Js
Dr. Ray Birge/2:54: "The immune system is very complex and if it can recognize tumors as being foreign to the body, then it can reactivate & eliminate these tumors to treat as a chronic disease, or in some cases eliminate the tumors. One of the projects that our lab is interested in is how to reactivate the immune system toward particular cancers, and we believe that the type of cell death that cancer cells undergo will determine whether or not they'll be an immune reaction against the cancer. If cells die, through a process called apoptosis, in a certain way, they can reactivate / activate the immune system and give a durable, anti-tumor response. The problem that we're trying to understand is how the tumor cells evade the immune system and therefore block these immune-suppressing signals to reactivate the immune system against cancer..."

[cjgaddy]

10-24-16: Duke’s Herbert.Lyerly presents AntiPS/TNBC data at AACR’s “Tumor Immunology and Immunotherapy Conference” in Boston. We first learned of the DUKE/PPHM Cancer Collab. in Bavi/TNBC back in Nov. 2015 at SITC'15 (See 11-9-15: Duke’s Dr. Herbert K. Lyerly http://tinyurl.com/pbof95w )...

10-24-16: Preclinical Research Demonstrates Peregrine Pharmaceuticals' PS-Targeting Antibodies Enhance the Anti-Tumor Activity of PD-L1 Checkpoint Inhibitors in Model of Triple Negative Breast Cancer (TNBC)
* Combination of PS-Targeting Antibody and Anti-PD-L1 Therapy, With or Without Chemotherapy, Led to Greater Anti-Tumor Activity Than Single Agent Treatment or Dual Combinations With Chemotherapy
* Additional Experiments Demonstrate that PS Expression is Upregulated on Cancer Cells Following Chemotherapy, Radiation or Photodynamic Therapy
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=994994

TUSTIN, Oct. 24, 2016: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, today announced the presentation of preclinical study data demonstrating that phosphatidylserine (PS)-targeting antibodies similar to bavituximab are able to enhance the anti-tumor activity of anti-PD-L1 therapy in a model of triple negative breast cancer (TNBC). Data showed that a combination of anti-PS and anti-PD-L1 therapies, with or without paclitaxel, led to greater anti-tumor responses than any of the treatments administered as single agents or dual treatment combinations with paclitaxel, in the well-characterized E0771 murine model of TNBC. Study results were presented by researchers from Duke University Medical Center at the American Association for Cancer Research's [AACR’s] Tumor Immunology and Immunotherapy Conference held October 20-23, 2016 in Boston, MA.

[ http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=92
10-22-16 POSTER SESSION B:
#B36 Modulating The Tumor Microenvironment to Enhance Cancer Immunotherapy by Inducing Phosphatidylserine Expression on the Tumor Surface”
Kensuke Kaneko 1, Takuya Osada 1, Bruce D. Freimark 2, Herbert Kim Lyerly ** (Duke Univ.) 1
1=Duke University, Durham, NC
2=Peregrine Pharmaceuticals, Inc.
**Dr. Herbert Kim Lyerly: https://immunology.duke.edu/people/herbert-kim-lyerly-md (George Barth Geller Professor, Duke Univ. MC)

In addition to evaluating the anti-tumor activity of the various treatment combinations, researchers also examined the impact of various traditional cancer therapies on PS expression in cancer cells. Study results confirmed that levels of PS expression were upregulated in E0771 and 4T1 TNBC cells following treatment with chemotherapy, radiation or photodynamic therapy. Photodynamic therapy also was shown to increase PS expression on tumor cells.

"These study results provide the latest support for the belief that PS-targeting therapies can enhance the anti-tumor activity of checkpoint inhibitors such as anti-PD-L1 therapy in the treatment of TNBC. Just last month, we announced results from another preclinical study [9-27-16/AACR-CRI: http://tinyurl.com/zy9yv78 ] in TNBC demonstrating that 80% of animals receiving the triple combination of anti-PS, anti-PD-1 and anti-LAG3 therapies experienced complete tumor regressions, whereas there were no animals in the anti-PD-1 and anti-LAG3 combination treatment arm that had a complete regression," said Jeff T. Hutchins, Ph.D., Peregrine's VP, Preclinical Research. "Additionally, these latest study findings related to increased PS expression on the surface of tumor cells following traditional cancer treatments demonstrate important activity within the tumor microenvironment that offers rationale for the potential of anti-PS agents in combatting cancer. We plan to continue to work with our collaborators at Duke University Medical Center to further study the therapeutic potential of PS-targeting agents in combination with checkpoint inhibitors like anti-PD-L1 and conventional therapies that augment immunotherapy mechanisms."

Bavituximab is an investigational monoclonal antibody that targets PS. Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. Previous studies demonstrated PS-targeting antibodies shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor responses. Peregrine evaluates the preclinical equivalent of bavituximab, ch1N11, in animal model studies to guide clinical development.

Peregrine's clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations [See: http://tinyurl.com/gutgwb5 ]. Those trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents [see MSKCC Wolchok Lab SITC'16 Nov9-13 2016: http://tinyurl.com/j4tw5p9 ]. The intent behind this strategy is to focus our research and development spending to further validate bavituximab's combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.

ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit http://www.peregrineinc.com .
Safe Harbor *snip*
CONTACTS:
Stephanie Diaz (Investors), Vida Strategic Partners, 415-675-7401, [e-mail]
Tim Brons (Media), Vida Strategic Partners, 415-675-7402, [e-mail]

= = = = = = = = = = =
BAVI MOA 9-27-16 AACR-CRI/Dr. Michael Gray: Preclin. Triple-Combo Bavi+PD1+LAG3 TNBC data in TNBC (80% Compl. Regression, Stat-Sig. Incr. in Key Tumor Fighting Immune Cells) http://tinyurl.com/zy9yv78

BAVI MOA 5-11-16 Breast Cancer Res. article, B.Freimark/CW.Hughes-et-al, “PS-Targeting/Bavi Combo w/Anti-PD1/PDL1 in Triple.Neg-MBC” http://tinyurl.com/zxu882y
...”our observations demonstrate that including PS-targeting antibodies such as bavituximab can enhance the anti-tumor activity of anti-PD-1/PD-L1 treatments, not only by increasing TIL responses but also by inhibiting cytokines stimulated by single-agent anti-PD-1 therapy that serve to suppress the immune response & promote tumor progression.”

BAVI MOA 4-20-16/AACR'16 & 4-4-16/Cancer-Immunology-Res.(AACR) article - preclin. data: Bavi combo w/anti-PD-1/anti-CTLA-4 “induces a shift in tumor microenvironment from immunosuppressive to immune active” http://tinyurl.com/jyox458

BAVI MOA 1-18-16: CEO Steve King explains PPHM's direct PS-Targeting advantage vs. the “individual-receptors” PS-binding approach of others like: Axl Mer TIM-3 RAGE Tyro3 GAS6 CD300a BAI1 MFG-E8 etc. http://tinyurl.com/h2h87mc

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.”
–----
11-9-15: BREAST CANCER - Researchers from Duke University and Peregrine evaluated the combination of ch1N11 (preclinical bavituximab equivalent) and anti-PD-1 therapy versus anti-PD-1 stand-alone therapy in well-characterized murine breast cancers, including the triple negative breast cancer (TNBC) model E0771. Study data showed that the combination therapy significantly enhanced overall survival (p=0.0016) and was capable of mediating complete tumor regressions in a greater number of subjects compared to single agent treatments (60% vs. 20%). Data also demonstrated that animals receiving combination treatment had significant increases in tumor associated indicators of immune system activation, including CD45+, CD8+ and CD3+ T-cells. Importantly, the combination treatment led to a prolonged anti-tumor immune response which protected the animals against a re-challenge with the same tumor. This sustained anti-tumor response suggests the potential of the combination therapy to trigger immune system memory and support adaptive immune responses against reemerging disease in breast cancers. All study animals experienced no signs of adverse effects following repeated doses of all therapeutic agents.

BAVI MOA 8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow http://tinyurl.com/qz64pzg
…“Expansion & Activation of T Cells via the Targeting of the Immunosuppressive Ligand PS: Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy”
5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x

• PGN632 (B2GPI-indep.) is 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

[biopharm]

Immunoscore and Bernard A Fox ...hmmmm

It looks like John Stafford left Xencor JUST IN TIME as he just missed the arrival of Raphael Clynes (ex BMS)

June 8, 2017
Xencor Appoints Raphael Clynes, M.D., Ph.D., as Vice President of Translational Biology
https://www.firstwordpharma.com/node/1478610
_________________________

Novel technologies and emerging biomarkers for personalized cancer immunotherapy

Jianda Yuan1Email author, Priti S. Hegde2, Raphael Clynes3, Periklis G. Foukas4, 5, Alexandre Harari4, Thomas O. Kleen6, Pia Kvistborg7, Cristina Maccalli8, Holden T. Maecker9, David B. Page10, Harlan Robins11, Wenru Song12, Edward C. Stack13, Ena Wang14, Theresa L. Whiteside15, Yingdong Zhao16, Heinz Zwierzina17, Lisa H. Butterfield18 and Bernard A. Fox10Email author
Journal for ImmunoTherapy of Cancer20164:3
https://doi.org/10.1186/s40425-016-0107-3©; Yuan et al. 2016
Received: 19 November 2015Accepted: 5 January 2016Published: 19 January 2016

https://jitc.biomedcentral.com/articles/10.1186/s40425-016-0107-3

____________

There are others of significance (David Pave...Butterfield...etc etc) but now after showing ties from Ronin group nominees to CSM ..etc ...etc and just now back to Xencor with FC binding domains and Xencor - Merck agreements.....and now to Mr Clynes ex BMS...

A $2.9 Billion Medarex style like sell off transfer would seem possible by Ronin group .... I will continue to buy after seeing these puzzle pieces and all it says is Ronin group / John Stafford seem to know PS Targeting is worth much more than $2.9 Billion

[biopharm]

"We are very pleased with the performance of the Opal assay, particularly its ability to compare the interaction of up to 6 phenotypic and functional markers on a single slide of tissue. The power and prognostic value of such immune activity assessments in the area of cancer was initially established by the Immunoscore [ http://www.immunoscore.org ], and we believe the Opal assay represents an important evolution of that work," said Bernard A. Fox, Ph.D., Harder Family Endowed Chair for Cancer Research, Member and Chief, Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center; a world-renowned translational cancer immunotherapist; a founding member of the Immunoscore steering committee [ http://www.ohsu.edu/xd/education/schools/school-of-medicine/academic-programs/graduate-studies/faculty/grad-studies-faculty.cfm?facultyid=104 ]. "I am looking forward to continued collaboration with Peregrine to further optimize and validate this assay to improve our understanding of immune infiltrate in tumors thereby facilitating the rational design and use of bavituximab in combination with novel and standard therapies."

Bernard Fox / BeiGene ...etc

https://www.drugs.com/conferences/ici-boston-summit-21329/