Replies to post #287840 on Avid Bioservices Inc (CDMO)

[cjgaddy]

Cedars-Sinai Researcher lists PPHM in her Disclosures in this Joint Mem.Sloan/Cedars-Sinai AACR’17 Abstract, where she's the Lead Author, along with co-authors Jedd Wolchok, Taha Merghoub, and several other Mem. Sloan researchers. So, 2 of Dr. Wolchok’s 5 AACR’17 abstracts are Joint PPHM+MemSloan, and a 3rd is Joint CedarsSinai+MemSloan whereby the Lead Author lists Peregrine in her disclosures. Maybe we need to add Cedars-Sinai to our collabs list along with Memorial Sloan Kettering, Duke, MDA, Rutgers, ImmunoVaccine, and UTSW.

AACR’17 4-4-17 #4705 “CTLA4 blockade with HER2-directed therapy yields clinical benefit in women undergoing Rad therapy (RT) for HER2+ breast cancer brain metastases”
Session: Immunomodulatory Agents & Therapeutics
Presenter/Authors:
Heather L. McArthur 1[Lead author, MD/MPH], Kathryn Beal 2, Darragh Halpenny 2, Micaela Henrich 2, Shanu Modi 2, Sujata Patil 2, Robert Young 2, Thomas Kaley 2, Taha Merghoub 2, Christopher Barker 2, Phillip Wong 2, Nicola Hamilton 2, Clifford Hudis 2, Jedd Wolchok 2, Larry Norton 2
1=Cedars-Sinai Medical Center, Los Angeles
2=Memorial Sloan Kettering Cancer Ctr., NYC
Disclosures:
Heather McArthur: Merck; OBI Pharma; Bristol Myers Squibb; Eli Lilly; MedImmune, AstraZeneca; Roche; Celgene; Calithera; Peregrine; Spectrum Pharm.
http://www.abstractsonline.com/pp8/#!/4292/presentation/6249
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Breast Cancer Res. Foundation (BCRF) Bio: Heather L. McArthur, MD, MPH
Medical Director, Breast Oncology, Cedars-Sinai Medical Center, Los Angeles
https://www.bcrfcure.org/researchers/heather-l-mcarthur
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NOTE: Mem. Sloan’s JEDD WOLCHOK is co-author of 5 AACR’17 Posters. 2 of the 5 are w/PPHM re: PS-Targeting. Only one other is with a biotech: Genocea Biosciences. The 4th is MSKCC ONLY, and the 5th is jointly w/Cedars-Sinai/LA. http://www.abstractsonline.com/pp8/#!/4292
PEREGRINE (Joint Mem.Sloan Kettering Wolchok Lab & PPHM):
1. 4-2-17 #574 “Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma” <=same as SICT’16/11-14-16
2. 4-3-17 #1651 “Targeting Phosphatidylserine in Combination With Adoptive T Cell Transfer Eliminates Advanced Tumors Without Off-Target Toxicities in a Melanoma Preclin. Model” <=New(2nd) PPHM+MSK/Wolchok
NON-PEREGRINE:
3. (MSK ONLY): 4-2-17 #874 “Lifting the iron curtain: Imaging cellular barriers to combination chelation-immune checkpoint therapy”
4. (MSK & Genocea Bio. http://www.genocea.com GNCA/$130mm MktCap) 4-2-17 #632 “Genome-scale neoantigen screening using ATLAS™ prioritizes candidate antigens for immunotherapy in a NSCLC patient”
=>5. (MSK & Cedars-Sinai/LA) 4-4-17 #4705 “CTLA4 blockade with HER2-directed therapy yields clinical benefit in women undergoing Rad therapy for HER2+ breast cancer brain metastases” <=Note: Lead Author Heather L. McArthur, Medical Dir./Breast Oncology at Cedars-Sinai MC, lists PPHM in her disclosures.

[cjgaddy]

AACR’17(Apr2-4), 5 PPHM ABSTRACTS: 2/MemSloan, 1/Immunovaccine, 1/PPHM-Only. There’s also a 5th one (PPHM, Vanderbilt, Precision-for-Medicine, Providence CC) in the “Ph2/3 Clinical Trials” session, whose Abstract is still embargoed: “CT159/25: IFN-y Analysis in Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” – is this a new (3rd) Sunrise Biomaker analysis?? - see below.
...Add ImmunoVaccine Inc. (Halifax https://www.imvaccine.com ) to the list of collaborators.
...#1651(Apr3) is the newly revealed 2nd joint PPHM+Mem.Sloan/Wolchok preclin. study: “PS Targeting + Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Model” - see more below.
...Memorial Sloan’s Dr. Jedd. Wolchok is co-author of 5 AACR’17 Posters: 2 of the 5 are w/PPHM re: PS-Targeting. Only one other is with a biotech: Genocea Biosciences. The 4th is MSKCC ONLY, and the 5th is jointly w/Cedars-Sinai/LA.

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Apr1-5 2017: “AACR 2017”, WashDC http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=105
Abstracts: http://www.abstractsonline.com/pp8/#!/4292
SUMMARY of PPHM’s 5 AACR’17 ABSTRACTS:
1. MSKCC+PPHM: 4-2-17/1pm #574, “PSTargeting+RAD+AntiPD1 Promotes Anti-Tumor Activity, Melanoma” (same as SITC'16/11-14-16 http://tinyurl.com/js3fca4 )
2. MSKCC+PPHM: 4-3-17/8am #1651, “PSTargeting+Adoptive TCell Transfer (ACT) Eliminates Adv. Tumors w/o Off-Target Toxicities, Melanoma” <=NEW(2nd) Joint MemSloan/PPHM study, see: http://tinyurl.com/h3ylrku
3. PPHM: 4-4-17/8am #3652, “PSTargeting+LAG3+AntiPD1 Significantly Enhances Anti-Tumor Activity, Triple- MBC”
4. IMMUNOVACCINE+PPHM: 4-4-17/8am #3657, ”PSTargeting Enhances Anti-Tumor Activity of a Tumor Vaccine(DepoVax), HPV-Induced Tumor” https://www.imvaccine.com
5. PPHM+VANDERBILT+PRECISIONMEDICINE+PROVIDENCECC: 4-3-17/1pm #CT159/25 (Session: Phase II/III Clinical Trials in Progress), “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” (Abstracts still embargoed a/o 3-1-17 5:45pmET)

AACR’17 DETAILS (5 PPHM ABSTRACTS)...
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1. 4-2-17/1pm #574 - Session: CHECKPOINTS 1
“Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma”
=> Sadna Budhu 1, Olivier De Henau 1, Roberta Zappasodi 1, Rachel Giese 1, Luis F. Campesato 1, Christopher Barker 1, Bruce Freimark 2, Jeff Hutchins 2, Jedd D. Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]
1=Memorial Sloan Kettering CC, NYC [ http://www.mskcc.org/research-areas/labs/jedd-wolchok ]
2=Peregrine Pharmaceuticals
NOTE: SAME TITLE AS WAS PRESENTED BY Mem.Sloan 11-14-16 SITC’16: see http://tinyurl.com/js3fca4
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid that is exposed on surface of apoptotic cells, tumor cells and tumor endothelium. PS has been shown to promote immunosuppressive signals in the tumor microenvironment. Antibodies that target PS have been shown to reactivate anti-tumor immunity by polarizing tumor associated macrophages into a pro-inflammatory M1 phenotype, reducing the number of MDSCs in tumors and promoting the maturation of dendritic cells into functional APCs. In a mouse B16 melanoma model, targeting PS in combination with immune checkpoint blockade promoted greater anti-tumor activity than either agent alone. This combination was shown to enhance CD4+ and CD8+ T cell infiltration and activation in the tumors of treated animals. Radiation therapy (RT) is an effective focal treatment of primary solid tumors, but is less effective in treating metastatic solid tumors as a monotherapy. There is evidence that RT induces immunogenic tumor cell death and enhances tumor-specific T cell infiltration in treated tumors. The abscopal effect, a phenomenon in which tumor regression occurs outside the site of RT, has been observed in both preclinical and clinical trials when RT is combined with immunotherapy. In this study, we show that irradiation treatment of B16 melanoma causes an increase in PS expression on the surface of viable tumor and immune infiltrates. We subsequently examined the effects of combining RT with an antibody that targets PS (mch1N11) [“Mouse version of Bavituximab”] and immune checkpoint blockade (anti-PD-1) in B16 melanoma. We found that treatment with mch1N11 synergizes with RT to improve anti-tumor activity and overall survival in tumor bearing mice. In addition, the triple combination of mch1N11, RT and anti-PD-1 treatment displayed even greater anti-tumor and survival benefit. Analysis of local immune responses in the tumors of treated animals revealed an increase in tumor-associated macrophages with a shift towards a pro-inflammatory M1 phenotype after treatment with RT and mch1N11. In addition, analysis of the systemic immune responses in the spleen and tumor draining lymph nodes revealed an increase in CD8 T cell activation, effector cytokine production and differentiation into effector memory cells in the triple combination. This finding highlights the potential of combining these 3 agents to improve outcome in patients with advanced-stage melanoma and other cancers and may inform the design of clinical studies combining PS-targeting antibodies with RT and/or checkpoint blockade.

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2. 4-3-17/8am #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS
“Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” <=NEW(2nd) MSK STUDY$$$
…...$$$See: More on the Significance of the New MSK/Wolchok+PPHM “ACT” study: http://tinyurl.com/h3ylrku
=> Daniel Hirschhorn-Cymerman 1, Sara Sara Schad 1, Sadna Budhu 1, Zhong Hong 1, Xia Yang 1, Hutchins T. Jeff 2, Bruce D. Freimark 2, Michael J. Gray 2, Jedd Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]
1=Memorial Sloan Kettering CC, NYC [ http://www.mskcc.org/research-areas/labs/jedd-wolchok ]
2=Peregrine Pharmaceuticals
ABSTRACT:
A viable strategy to treat advanced cancers includes transferring of tumor-specific T cells. T cells that recognize tumor antigens can be expanded and reinvigorated ex-vivo. Furthermore, autologous T cells can be genetically modified to express anti-tumor T cell receptors or chimeric antigen receptors. Although the potency and specificity of tumor-specific T cells can be manipulated ex-vivo, once re-infused into patients, the T cells are subjected to immunosuppressive mechanisms established by the tumor. An important immune checkpoint regulator within tumors is phosphatidylserine (PS). Innate immune cells exposed to PS secrete suppressive cytokines and chemokines that can significantly impair the function and activation of anti-tumor T cells. Therefore, monoclonal antibodies that block PS activity can increase the anti-tumor potency of transferred T cells to treat aggressive cancers. Here we show that a PS targeting monoclonal antibody in combination with CD4+ T cells that recognize the melanoma antigen Trp1 can regress very advanced melanomas in all treated mice. Combination of anti-Trp1 CD4+ T cells with other immunomodulatory modalities such as anti-OX40 antibodies, can achieve equivalent treatment rates but these are typically accompanied by severe immune related adverse events. In contrast, in this setting, PS blockadedid not show any off-target toxicities. Flow cytometry analysis revealed lower levels of CD206 expression concomitant with higher activation markers in macrophages and neutrophils in tumors from anti-PS treated mice. These results suggest that diminishing suppressive mechanisms locally in adoptive transfer protocols is a highly desirable strategy that can eliminate tumors while minimizing related adverse events.
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NOTE1:
From 3-2014 Immunotherapy article: “Cancer immunotherapy, particularly adoptive cell transfer (ACT), has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to std. Therapies” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372895
NOTE2:
Through the support from SEAN PARKER, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed an Immunology Research Dream Team dedicated to cancer immunology: “Immunologic Checkpoint Blockade & Adoptive Cell Transfer in Cancer Therapy.” The Immunotherapy Dream Team is focused on 2 approaches for this translational cancer research project, which will unite laboratory & clinical efforts towards the immunological treatment, control, and prevention of cancer.
The 1st is investigating blockades (by inhibitory molecules called “checkpoints”) of T lymphocytes’ inhibitory receptors, which block immune responses; and the use of antibodies to remove the checkpoints, once again allowing white blood cells called T lymphocytes to kill the cancer cells.
Second, the Immunotherapy Dream Team is pursuing multiple Adoptive Cell Transfer (ACT) approaches, which increase immunity.”
DREAM TEAM LEADERSHIP: 10 scientists, incl. MSKCC’s Jedd D. Wolchok & Michel Sadelain.
http://parker.org/initiatives/immunotherapy

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3. 4-4-17/8am #3652 - Session: BITES BISPECIFICS & CHECKPOINTS
“Combinational Activity of LAG3 & PD-1 Targeted Therapies is Significantly Enhanced by the Addition of Phosphatidylserine Targeting Antibodies and Establishes an Anti-Tumor Memory Response in Murine Triple Negative Breast Cancer”
=> Michael J. Gray, Jian Gong, Jeff Hutchins, Bruce Freimark (Peregrine Pharmaceuticals)
ABSTRACT:
Previous studies utilizing NanoString immune profile analysis demonstrated that intratumoral levels of LAG3 (lymphocyte activation gene 3) mRNA increased in response to phosphatidylserine (PS) and PD-1 targeting antibodies in murine triple negative breast cancers (TNBC). This suggests LAG3 acts to attenuate immune system activation during I/O therapies - and that PD-1 and LAG3 function cooperatively in suppressing immune system activation. Here we show that adding PS targeting antibodies can further enhance the effectiveness of antibodies targeting LAG3 and/or LAG3+PD-1. We first examined expression of LAG3 and PD-1 in the murine TNBC model E0771 and found that tumor associated T-cells (CD4+ and CD8+) have expression of both markers. Mice implanted with TNBC tumors were next treated with antibodies targeting PS, PD-1, and LAG3 alone and in combination with each other. Interestingly, the addition of PS targeting antibodies not only increased the effectiveness anti-PD-1 effectiveness as previously observed, but also enhanced anti-LAG3 treatment, showing that PS targeting antibodies are capable of augmenting additional I/O therapeutic regimens. Comparison of anti-PD-1+LAG3 combination vs. single anti-PD-1 or anti-LAG3 treatments showed moderately more anti-tumor activity than single treatments, however the addition of PS targeting antibodies to either checkpoint inhibitor was as equally effective in inhibiting tumor growth as observed in the anti-LAG3+PD-1 treatment. Further comparison of antibody treatments targeting PD-1+LAG3 vs. PS+PD-1+LAG3 demonstrated that the addition of PS targeting antibodies resulted in a significant decrease in tumor growth with complete tumor regression in 80% of the animals (along with the ability to completely reject secondary TNBC challenge) compared to 0% in the anti-PD-1+LAG3 treatment group. Immunoprofiling showed that the addition of PS targeting antibodies to these checkpoint therapies, including the combination of anti-PD-1+LAG3, resulted in a phenotype associated with enhanced immune system activation and immune-surveillance including increased tumor infiltrating lymphocytes (TILs) with upregulation of T-cell associated activation pathways, increased Th1 to Th2 profile, and enhanced antigen presentation processing /presentation mechanisms along with cytokines associated with immune system activation. Overall our data demonstrate that adding PS targeting antibodies to clinically relevant therapies, including PD-1 and LAG3, may significantly enhance their ability to activate and redirect the host immune system into recognition and elimination of tumor cells compared to single and combinational treatments that lack PS targeting antibodies.

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4. 4-4-17/8am #3657 - Session: BITES BISPECIFICS & CHECKPOINTS
”Phosphatidylserine-Targeting Antibodies Enhance Anti-Tumor Activity of a Tumor Vaccine in a HPV-Induced Tumor Model”
=> Genevieve Weir 1, Tara Quinton 1, Jeff T. Hutchins 2, Bruce D. Freimark 2, Marianne Stanford (VP/Res., Immunovaccine)
1=Immunovaccine, Inc., Halifax, NS, Canada [ https://www.imvaccine.com ]
2=Peregrine Pharmaceuticals
[Note: clearly, this study is combining PPHM’s Anti-PS with ImmunoVaccine’s DepoVax Vaccine Adjuvanting Platform https://www.imvaccine.com/depovax.php ]
ABSTRACT:
Antibodies targeting phosphatidylserine (PS) have been shown to induce anti-tumor responses by induction of tumor-specific T cells. Based on this observation, we evaluated the responses of PS and PD-1 targeting antibody therapy to enhance anti-tumor responses of a HPV16 peptide vaccine formulated in DepoVax (DPX) in mice bearing HPV-transformed C3 mouse tumors. The addition of PS-targeting antibody (mch1N11) [“Mouse version of Bavituximab”] to DPX/metronomic cyclophosphamide (mCPA) immunotherapy prolonged survival in comparison to mice receiving an isotype control in combination with DPX/mCPA. When anti-PD-1 was added to mch1N11 + mCPA, there was no increase in survival. The addition of mch1N11 to DPX/mCPA immunotherapy had no effect on tumor growth or survival in the aggressive B16-F10 model. TIL analysis revealed an increase in CD8+ T cells, antigen specific CD8+ T cells and PD-1+ T cells in the tumor with mch1N11 treatment. The expression of surface markers for macrophages (CD68high, F4/80) and dendritic cells (CD11c) were also increased in the tumors of mice treated with mch1N11. RT-qPCR analysis of the tumor confirmed higher mRNA expression of T cells markers (CD8, Granzyme B, PD-1) and antigen presenting cell markers (F4/80, CD74). In the spleen, expression of cell surface markers for monocytes (CD11b) and PD-1+ T cells (CD8) were elevated in groups treated with mch1N11 in combination with anti-PD-1. Combined, these findings indicate that in this model, PS-targeting antibodies can enhance the activity of phagocytic cells involved in antigen presentation. We have found that PD-1 expression increases as anti-tumor activity increases, therefore these results also provide an indication that antibodies targeting PS enhance the anti-tumor immune response induced by DPX/mCPA therapy. The observations suggest that PS-targeting antibodies may enhance therapeutic vaccines for the treatment of cancer.

= = = = = = = = = =IS THIS A NEW (3RD) SUNRISE BIOMAKER ANALYSIS??
5. 4-3-17/1pm #CT159/25 - Session: Phase III Clinical Trials & Phase II/III Clinical Trials in Progress
http://www.abstractsonline.com/pp8/#!/4292/presentation/12566
”CT159 / 25 - IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker”
=> Nikoletta Kallinteris 1, Leora Horn 2, Min Tang 1, Tobias Guennel 3, Shen Yin 1, Jennifer Lai 1, Joseph Shan 1, Rachel E. Sanborn (Providence CC)*** 4
1=Peregrine Pharmaceuticals
2=Vanderbilt-Ingram Cancer Center, Nashville, TN
3=Precision for Medicine, Frederick, MD
4=Providence Cancer Center, Portland, OR
***Rachel Sanborn MD, Dir./Thoracic-Oncology, Providence CC http://cancergrace.org/faculty/rachel-sanborn-md - Dr. Sanborn's Conflicts of interest: DNA, AZN
ABSTRACT: Still Embargoed a/o 3-1-17 5:45pmET.
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Is this AACR’17 #5 perhaps the 3rd Sunrise Biomarker??? It does not look like #2 (12-7-16 WCLC’16(IASLC)/Vienna) that was canceled due to “work not complete”...
Sunrise Biomarkers/UTSW’s Dr. David Gerber:
#1=B2GPI: 10-10-16 http://tinyurl.com/hp73njt
#2=Complement & IL-10 Pathways(12-7-17/IASLC delayed, “not done”, after prelim. abstract said, “Pts=193, within the 1st subgroup of N=104, a 2nd subgroup isolated: MOS 5.9=>12.5mos”
#3=???
The results of th the Biomarkers analysis may drive into the design of the 3 planned NCCN human trials and the AZN Bavi+Durva ‘Mult. Solid Tumors’ trial, the design of which is currently “under evaluation”. See http://tinyurl.com/jbv3ms5
...Recall: #2: 12/7/16/Vienna/WCLC’16/Canceled:
”A Pre-Treatment Serum Test Based on Complement & IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel”
David E. Gerber [UTSW], J. Roder, N.L. Kallinteris, L. Horn, G. Losonczy, R. Natale, M. Tang, Heinrich Roder[CTO, Biodesix http://www.biodesix.com/project/heinrichroder ], Joe S. Shan [VP/Clin+Reg], Rachel E. Sanborn [Providence Portland Medical Ctr]

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INTERESTING: Mem. Sloan’s Dr. Jedd. Wolchok is co-author of 5 AACR’17 Posters. 2 of the 5 are w/PPHM re: PS-Targeting. Only one other is with a biotech: Genocea Biosciences. The 4th is MSKCC ONLY, and the 5th is jointly w/Cedars-Sinai/LA. http://www.abstractsonline.com/pp8/#!/4292 .
PEREGRINE (Joint Mem.Sloan Kettering Wolchok Lab & PPHM):
1. 4-2-17 #574 “Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma” <=Same as SITC’16 11-14-16.
2. 4-3-17 #1651 “Targeting Phosphatidylserine in Combination With Adoptive T Cell Transfer Eliminates Advanced Tumors Without Off-Target Toxicities in a Melanoma Preclin. Model” <=NEW/2nd PPHM+MSK.
NON-PEREGRINE:
3. (MSK ONLY): 4-2-17 #874 “Lifting the iron curtain: Imaging cellular barriers to combination chelation-immune checkpoint therapy”
4. (MSK & Genocea Bio. http://www.genocea.com GNCA/$130mm MktCap) 4-2-17 #632 “Genome-scale neoantigen screening using ATLAS™ prioritizes candidate antigens for immunotherapy in a NSCLC patient”
5. (MSK & Cedars-Sinai/LA) 34-4-17 #4705 “CTLA4 blockade with HER2-directed therapy yields clinical benefit in women undergoing radiation therapy for HER2+ breast cancer brain metastases”

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2-12-17: Preclin. Anti-PS work w/collab’s MemSloan, Duke, MDA, Rutgers, Wistar, ImmunoVaccine Inc… http://tinyurl.com/gof4kua

BAVI MOA 11-14-16: SITC’16: Joint Memorial Sloan Kettering (Wolchok Lab) & PPHM poster on Triple Combo Rad+Bavi+aPD1 vs. Melanoma http://tinyurl.com/js3fca4
“PS Targeting Antibody in Combination with Checkpoint Blockade & Tumor Radiation Therapy Promotes Anti-Cancer Activity in Mouse Melanoma” (same as AACR’17 4-2-17 #574)
DR. JEDD WOLCHOK: "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."
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."

5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8
...Dr. Wolchock states, ”The phosphatidylserine (PS) signaling pathway is a very interesting target for modulating the immune system's response to cancer. We look forward to exploring the potential of PS-targeting agents alone and with other immune modulators that may lead to novel advances in cancer therapy.”
...Dr. Taha Merghoub states, "A key focus of the Wolchok Lab's research is studying novel immunotherapy combinations that work together to enable the immune system to recognize & destroy cancer. This collaboration will allow us to focus on the role & contribution of PS blockade therapy in determining which combination of the current & next gen. of immune modulators is likely to increase the extent & amplitude of anti-tumor response. This important pre-clinical and translational work will potentially guide the design of the next gen. of clinical studies with bavituximab.”

POSSIBLE GENESIS OF IMMUNOVACCINE COLLAB???
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.”

SITC’16 PPHM/Mem.Sloan Poster – same as AACR’17 4-2-17 #574…

[cjgaddy]

Known Upcoming Events (incl. AACR’17 w/New MSK/Wolchok, NEW-BIOMARKER)

Mar13(Monday): FY'17Q3 (qe 1-31-17) Financials & Conf. Call - http://ir.peregrineinc.com/events.cfm

Mar14/Avid: Repligen Corp's "Driving Bioprocessing Efficiency Seminar", Carlsbad http://www.repligen.com/sandiego2017 PR: http://tinyurl.com/zbflrcf
...2:45pm: Dr. David Briggs (Avid Scientist), "Case study: Positive Impact of Pre-packed Columns in a Multi-product Mfg. Facility"

Apr1-5: AACR 2017, WashDC http://tinyurl.com/zdsbds8 [See DETAILS below]
SUMMARY of PPHM’s 5 AACR’17 ABSTRACTS:
1. MSKCC+PPHM: 4-2-17/1pm #574, “PSTargeting+RAD+AntiPD1 Promotes Anti-Tumor Activity, Melanoma” (same as SITC'16/11-14-16 http://tinyurl.com/js3fca4 )
2. MSKCC+PPHM: 4-3-17/8am #1651, “PSTargeting+Adoptive TCell Transfer (ACT) Eliminates Adv. Tumors w/o Off-Target Toxicities, Melanoma” <=NEW(2nd) Joint MemSloan/PPHM study, see: http://tinyurl.com/h3ylrku
3. PPHM: 4-4-17/8am #3652, “PSTargeting+LAG3+AntiPD1 Significantly Enhances Anti-Tumor Activity, Triple- MBC”
4. IMMUNOVACCINE+PPHM: 4-4-17/8am #3657, ”PSTargeting Enhances Anti-Tumor Activity of a Tumor Vaccine(DepoVax), HPV-Induced Tumor” https://www.imvaccine.com
5. PPHM+VANDERBILT+PRECISIONMEDICINE+PROVIDENCECC: 4-3-17/1pm #CT159/25 (Session: Ph2/3 Clinical Trials in Progress), “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” (abstract embargoed, Sunrise Biomarker #3?)

??Jun2-6: ASCO 2017, Chicago https://am.asco.org (Abstracts: Titles/MidAPR, Full=May17)

Jun19-22/Avid Booth #1411: BIO Intl. Convention, SanDiego http://www.convention.bio.org/2017

~Jul13: FY'17Q4 (fye 4-30-17) Financials & Conf. Call - http://ir.peregrineinc.com/events.cfm
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= = = = = = = = = = = = = = = = = =AACR’17(Apr2-4) DETAILS...
Apr1-5 2017: “AACR 2017”, WashDC http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=105
Abstracts: http://www.abstractsonline.com/pp8/#!/4292
5 PPHM ABSTRACTS: 2/MemSloan, 1/Immunovaccine, 1/PPHM-Only. There’s also a 5th one (#CT159/25: PPHM, Vanderbilt, Precision-for-Medicine, Providence CC) in the “Ph2/3 Clinical Trials” session, whose Abstract is still embargoed: “CT159/25: IFN-y Analysis in Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” – is this a new (3rd) Sunrise Biomaker analysis?? - see below.
...Add ImmunoVaccine Inc. (Halifax https://www.imvaccine.com ) to the list of collaborators.
...#1651(Apr3) is the newly revealed 2nd joint PPHM+Mem.Sloan/Wolchok preclin. study: “PS Targeting + Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Model” - see more below.
5 AACR’17 PPHM ABSTRACTS (DETAIL):
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1. 4-2-17/1pm #574 - Session: CHECKPOINTS 1
“Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma”
=> Sadna Budhu 1, Olivier De Henau 1, Roberta Zappasodi 1, Rachel Giese 1, Luis F. Campesato 1, Christopher Barker 1, Bruce Freimark 2, Jeff Hutchins 2, Jedd D. Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]
1=Memorial Sloan Kettering CC, NYC [ http://www.mskcc.org/research-areas/labs/jedd-wolchok ]
2=Peregrine Pharmaceuticals
NOTE: SAME TITLE AS WAS PRESENTED BY Mem.Sloan 11-14-16 SITC’16: see http://tinyurl.com/js3fca4
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid that is exposed on surface of apoptotic cells, tumor cells and tumor endothelium. PS has been shown to promote immunosuppressive signals in the tumor microenvironment. Antibodies that target PS have been shown to reactivate anti-tumor immunity by polarizing tumor associated macrophages into a pro-inflammatory M1 phenotype, reducing the number of MDSCs in tumors and promoting the maturation of dendritic cells into functional APCs. In a mouse B16 melanoma model, targeting PS in combination with immune checkpoint blockade promoted greater anti-tumor activity than either agent alone. This combination was shown to enhance CD4+ and CD8+ T cell infiltration and activation in the tumors of treated animals. Radiation therapy (RT) is an effective focal treatment of primary solid tumors, but is less effective in treating metastatic solid tumors as a monotherapy. There is evidence that RT induces immunogenic tumor cell death and enhances tumor-specific T cell infiltration in treated tumors. The abscopal effect, a phenomenon in which tumor regression occurs outside the site of RT, has been observed in both preclinical and clinical trials when RT is combined with immunotherapy. In this study, we show that irradiation treatment of B16 melanoma causes an increase in PS expression on the surface of viable tumor and immune infiltrates. We subsequently examined the effects of combining RT with an antibody that targets PS (mch1N11) [“Mouse version of Bavituximab”] and immune checkpoint blockade (anti-PD-1) in B16 melanoma. We found that treatment with mch1N11 synergizes with RT to improve anti-tumor activity and overall survival in tumor bearing mice. In addition, the triple combination of mch1N11, RT and anti-PD-1 treatment displayed even greater anti-tumor and survival benefit. Analysis of local immune responses in the tumors of treated animals revealed an increase in tumor-associated macrophages with a shift towards a pro-inflammatory M1 phenotype after treatment with RT and mch1N11. In addition, analysis of the systemic immune responses in the spleen and tumor draining lymph nodes revealed an increase in CD8 T cell activation, effector cytokine production and differentiation into effector memory cells in the triple combination. This finding highlights the potential of combining these 3 agents to improve outcome in patients with advanced-stage melanoma and other cancers and may inform the design of clinical studies combining PS-targeting antibodies with RT and/or checkpoint blockade.

= = = = = = = = = = = = = = = =
2. 4-3-17/8am #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS
“Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” <=NEW(2nd) MSK STUDY$$$
…...$$$See: More on the Significance of the New MSK/Wolchok+PPHM “ACT” study: http://tinyurl.com/h3ylrku
=> Daniel Hirschhorn-Cymerman 1, Sara Sara Schad 1, Sadna Budhu 1, Zhong Hong 1, Xia Yang 1, Hutchins T. Jeff 2, Bruce D. Freimark 2, Michael J. Gray 2, Jedd Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]
1=Memorial Sloan Kettering CC, NYC [ http://www.mskcc.org/research-areas/labs/jedd-wolchok ]
2=Peregrine Pharmaceuticals
ABSTRACT:
A viable strategy to treat advanced cancers includes transferring of tumor-specific T cells. T cells that recognize tumor antigens can be expanded and reinvigorated ex-vivo. Furthermore, autologous T cells can be genetically modified to express anti-tumor T cell receptors or chimeric antigen receptors. Although the potency and specificity of tumor-specific T cells can be manipulated ex-vivo, once re-infused into patients, the T cells are subjected to immunosuppressive mechanisms established by the tumor. An important immune checkpoint regulator within tumors is phosphatidylserine (PS). Innate immune cells exposed to PS secrete suppressive cytokines and chemokines that can significantly impair the function and activation of anti-tumor T cells. Therefore, monoclonal antibodies that block PS activity can increase the anti-tumor potency of transferred T cells to treat aggressive cancers. Here we show that a PS targeting monoclonal antibody in combination with CD4+ T cells that recognize the melanoma antigen Trp1 can regress very advanced melanomas in all treated mice. Combination of anti-Trp1 CD4+ T cells with other immunomodulatory modalities such as anti-OX40 antibodies, can achieve equivalent treatment rates but these are typically accompanied by severe immune related adverse events. In contrast, in this setting, PS blockadedid not show any off-target toxicities. Flow cytometry analysis revealed lower levels of CD206 expression concomitant with higher activation markers in macrophages and neutrophils in tumors from anti-PS treated mice. These results suggest that diminishing suppressive mechanisms locally in adoptive transfer protocols is a highly desirable strategy that can eliminate tumors while minimizing related adverse events.
----------
NOTE1:
From 3-2014 Immunotherapy article: “Cancer immunotherapy, particularly adoptive cell transfer (ACT), has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to std. Therapies” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372895
NOTE2:
Through the support from SEAN PARKER, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed an Immunology Research Dream Team dedicated to cancer immunology: “Immunologic Checkpoint Blockade & Adoptive Cell Transfer in Cancer Therapy.” The Immunotherapy Dream Team is focused on 2 approaches for this translational cancer research project, which will unite laboratory & clinical efforts towards the immunological treatment, control, and prevention of cancer.
The 1st is investigating blockades (by inhibitory molecules called “checkpoints”) of T lymphocytes’ inhibitory receptors, which block immune responses; and the use of antibodies to remove the checkpoints, once again allowing white blood cells called T lymphocytes to kill the cancer cells.
Second, the Immunotherapy Dream Team is pursuing multiple Adoptive Cell Transfer (ACT) approaches, which increase immunity.”
DREAM TEAM LEADERSHIP: 10 scientists, incl. MSKCC’s Jedd D. Wolchok & Michel Sadelain.
http://parker.org/initiatives/immunotherapy

= = = = = = = = = = = = = = = =
3. 4-4-17/8am #3652 - Session: BITES BISPECIFICS & CHECKPOINTS
“Combinational Activity of LAG3 & PD-1 Targeted Therapies is Significantly Enhanced by the Addition of Phosphatidylserine Targeting Antibodies and Establishes an Anti-Tumor Memory Response in Murine Triple Negative Breast Cancer”
=> Michael J. Gray, Jian Gong, Jeff Hutchins, Bruce Freimark (Peregrine Pharmaceuticals)
ABSTRACT:
Previous studies utilizing NanoString immune profile analysis demonstrated that intratumoral levels of LAG3 (lymphocyte activation gene 3) mRNA increased in response to phosphatidylserine (PS) and PD-1 targeting antibodies in murine triple negative breast cancers (TNBC). This suggests LAG3 acts to attenuate immune system activation during I/O therapies - and that PD-1 and LAG3 function cooperatively in suppressing immune system activation. Here we show that adding PS targeting antibodies can further enhance the effectiveness of antibodies targeting LAG3 and/or LAG3+PD-1. We first examined expression of LAG3 and PD-1 in the murine TNBC model E0771 and found that tumor associated T-cells (CD4+ and CD8+) have expression of both markers. Mice implanted with TNBC tumors were next treated with antibodies targeting PS, PD-1, and LAG3 alone and in combination with each other. Interestingly, the addition of PS targeting antibodies not only increased the effectiveness anti-PD-1 effectiveness as previously observed, but also enhanced anti-LAG3 treatment, showing that PS targeting antibodies are capable of augmenting additional I/O therapeutic regimens. Comparison of anti-PD-1+LAG3 combination vs. single anti-PD-1 or anti-LAG3 treatments showed moderately more anti-tumor activity than single treatments, however the addition of PS targeting antibodies to either checkpoint inhibitor was as equally effective in inhibiting tumor growth as observed in the anti-LAG3+PD-1 treatment. Further comparison of antibody treatments targeting PD-1+LAG3 vs. PS+PD-1+LAG3 demonstrated that the addition of PS targeting antibodies resulted in a significant decrease in tumor growth with complete tumor regression in 80% of the animals (along with the ability to completely reject secondary TNBC challenge) compared to 0% in the anti-PD-1+LAG3 treatment group. Immunoprofiling showed that the addition of PS targeting antibodies to these checkpoint therapies, including the combination of anti-PD-1+LAG3, resulted in a phenotype associated with enhanced immune system activation and immune-surveillance including increased tumor infiltrating lymphocytes (TILs) with upregulation of T-cell associated activation pathways, increased Th1 to Th2 profile, and enhanced antigen presentation processing /presentation mechanisms along with cytokines associated with immune system activation. Overall our data demonstrate that adding PS targeting antibodies to clinically relevant therapies, including PD-1 and LAG3, may significantly enhance their ability to activate and redirect the host immune system into recognition and elimination of tumor cells compared to single and combinational treatments that lack PS targeting antibodies.

= = = = = = = = = = = = = = = =
4. 4-4-17/8am #3657 - Session: BITES BISPECIFICS & CHECKPOINTS
”Phosphatidylserine-Targeting Antibodies Enhance Anti-Tumor Activity of a Tumor Vaccine in a HPV-Induced Tumor Model”
=> Genevieve Weir 1, Tara Quinton 1, Jeff T. Hutchins 2, Bruce D. Freimark 2, Marianne Stanford (VP/Res., Immunovaccine)
1=Immunovaccine, Inc., Halifax, NS, Canada [ https://www.imvaccine.com ]
2=Peregrine Pharmaceuticals
[Note: clearly, this study is combining PPHM’s Anti-PS with ImmunoVaccine’s DepoVax Vaccine Adjuvanting Platform https://www.imvaccine.com/depovax.php ]
ABSTRACT:
Antibodies targeting phosphatidylserine (PS) have been shown to induce anti-tumor responses by induction of tumor-specific T cells. Based on this observation, we evaluated the responses of PS and PD-1 targeting antibody therapy to enhance anti-tumor responses of a HPV16 peptide vaccine formulated in DepoVax (DPX) in mice bearing HPV-transformed C3 mouse tumors. The addition of PS-targeting antibody (mch1N11) [“Mouse version of Bavituximab”] to DPX/metronomic cyclophosphamide (mCPA) immunotherapy prolonged survival in comparison to mice receiving an isotype control in combination with DPX/mCPA. When anti-PD-1 was added to mch1N11 + mCPA, there was no increase in survival. The addition of mch1N11 to DPX/mCPA immunotherapy had no effect on tumor growth or survival in the aggressive B16-F10 model. TIL analysis revealed an increase in CD8+ T cells, antigen specific CD8+ T cells and PD-1+ T cells in the tumor with mch1N11 treatment. The expression of surface markers for macrophages (CD68high, F4/80) and dendritic cells (CD11c) were also increased in the tumors of mice treated with mch1N11. RT-qPCR analysis of the tumor confirmed higher mRNA expression of T cells markers (CD8, Granzyme B, PD-1) and antigen presenting cell markers (F4/80, CD74). In the spleen, expression of cell surface markers for monocytes (CD11b) and PD-1+ T cells (CD8) were elevated in groups treated with mch1N11 in combination with anti-PD-1. Combined, these findings indicate that in this model, PS-targeting antibodies can enhance the activity of phagocytic cells involved in antigen presentation. We have found that PD-1 expression increases as anti-tumor activity increases, therefore these results also provide an indication that antibodies targeting PS enhance the anti-tumor immune response induced by DPX/mCPA therapy. The observations suggest that PS-targeting antibodies may enhance therapeutic vaccines for the treatment of cancer.

= = = = = = = = = =IS THIS A NEW (3RD) SUNRISE BIOMAKER ANALYSIS??
#5. 4-3-17/1pm #CT159/25 - Session: Phase III Clinical Trials & Phase II/III Clinical Trials in Progress
http://www.abstractsonline.com/pp8/#!/4292/presentation/12566
”IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker”
=> Nikoletta Kallinteris 1, Leora Horn 2, Min Tang 1, Tobias Guennel 3, Shen Yin 1, Jennifer Lai 1, Joseph Shan 1, Rachel E. Sanborn (Providence CC)*** 4
1=Peregrine Pharmaceuticals
2=Vanderbilt-Ingram Cancer Center, Nashville, TN
3=Precision for Medicine, Frederick, MD
4=Providence Cancer Center, Portland, OR
***Rachel Sanborn MD, Dir./Thoracic-Oncology, Providence CC http://cancergrace.org/faculty/rachel-sanborn-md - Dr. Sanborn's Conflicts of interest: DNA, AZN
ABSTRACT: Embargoed – until 4/3/17??
-------
Is this AACR’17 #5 perhaps the 3rd Sunrise Biomarker??? It does not look like #2 (12-7-16 WCLC’16(IASLC)/Vienna) that was canceled due to “work not complete”...
Known Ph.3 Sunrise Biomarkers/UTSW’s Dr. David Gerber et al:
#1=B2GPI: 10-10-16 http://tinyurl.com/hp73njt
#2=Complement & IL-10 Pathways(12-7-17/IASLC delayed, “not done”, after prelim. abstract said, “Pts=193, within the 1st subgroup of N=104, a 2nd subgroup isolated: MOS 5.9=>12.5mos”
#3=???
The results of th the Biomarkers analysis may drive into the design of the 3 planned NCCN human trials and the AZN Bavi+Durva ‘Mult. Solid Tumors’ trial, the design of which is currently “under evaluation”. See http://tinyurl.com/jbv3ms5




- - - - - - - - - - - - - - - - - - -
INTERESTING: Mem. Sloan’s Dr. Jedd. Wolchok is co-author of 9 AACR’17 abstracts. 2 of the 9 are w/PPHM re: PS-Targeting. With biotechs, he has one each with Genocea Biosciences(ex-vivo screening), Infinity Pharm(Ph1), Leap Ther.(Ph1), and two with BMS(P1+3). The 8th is MSKCC ONLY, and the 9th is jointly w/Cedars-Sinai/LA. http://www.abstractsonline.com/pp8/#!/4292 .
PEREGRINE (Joint Mem.Sloan Kettering Wolchok Lab & PPHM):
1. 4-2-17 #574 “Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma” <=Same as SITC’16 11-14-16.
2. 4-3-17 #1651 “Targeting Phosphatidylserine in Combination With Adoptive T Cell Transfer Eliminates Advanced Tumors Without Off-Target Toxicities in a Melanoma Preclin. Model” <=NEW/2nd PPHM+MSK.
NON-PEREGRINE:
3. (MSK ONLY): 4-2-17 #874 “Lifting the iron curtain: Imaging cellular barriers to combination chelation-immune checkpoint therapy”
4. (MSK & Genocea Bio. http://www.genocea.com GNCA/$130mm MktCap) 4-2-17 #632 “Genome-scale neoantigen screening using ATLAS prioritizes candidate antigens for immunotherapy in a NSCLC patient”
5. (MSK & Cedars-Sinai/LA) 4-4-17 #4705 “CTLA4 blockade with HER2-directed therapy yields clinical benefit in women undergoing radiation therapy for HER2+ breast cancer brain metastases”
6. (MSK & Infinity Pharm.) 4-4-17 #CT089 “A Ph1, first-in-human study of IPI-549, a PI3K-y inhibitor, as monotherapy & in combo w/nivolumab in adv. solid tumors”
7. (MSK & Leap Ther.) 4-2-17 #CT018 “Intratumor & peripheral Treg modulation as a pharmacodynamic biomarker of the GITR agonist antibody TRX-518 in the 1st in-human trial”
8. (MSK & BMS) 4-3-17 #CT073 “(Ph1) Immunomodulatory effects of NIVO+IPI or NIVO/mono in adv. melanoma: CheckMate038”
9. (MSK & BMS) 4-3-17 #CT075 “OS results from a Ph3 of NIVO+IPI in treatment-naïve pts w/adv. Melanoma: CheckMate067”

= = = = = = = = = = = = =
2-28-17: Collabs with Mem.Sloan(Wolchok), Duke, MDA, Rutgers, ImmunoVaccine, UTSW… http://tinyurl.com/heg9t3v

BAVI MOA 11-14-16: SITC’16: Joint Memorial Sloan Kettering (Wolchok Lab) & PPHM poster on Triple Combo Rad+Bavi+aPD1 vs. Melanoma http://tinyurl.com/js3fca4
“PS Targeting Antibody in Combination with Checkpoint Blockade & Tumor Radiation Therapy Promotes Anti-Cancer Activity in Mouse Melanoma” (same as AACR’17 4-2-17 #574)
DR. JEDD WOLCHOK: "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."
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."

5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8
...Dr. Wolchock states, ”The phosphatidylserine (PS) signaling pathway is a very interesting target for modulating the immune system's response to cancer. We look forward to exploring the potential of PS-targeting agents alone and with other immune modulators that may lead to novel advances in cancer therapy.”
...Dr. Taha Merghoub states, "A key focus of the Wolchok Lab's research is studying novel immunotherapy combinations that work together to enable the immune system to recognize & destroy cancer. This collaboration will allow us to focus on the role & contribution of PS blockade therapy in determining which combination of the current & next gen. of immune modulators is likely to increase the extent & amplitude of anti-tumor response. This important pre-clinical and translational work will potentially guide the design of the next gen. of clinical studies with bavituximab.”

POSSIBLE GENESIS OF IMMUNOVACCINE COLLAB???
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.”

SITC’16 PPHM/Mem.Sloan Poster – same as AACR’17 4-2-17 #574…

[cjgaddy]

Mem.Sloan/Wolchok, Biomarkers, NCCN/AZN Trials – tightly related imo...

CHRONOLOGICALLY:
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8
JEDD WOLCHOK: ”The phosphatidylserine (PS) signaling pathway is a very interesting target for modulating the immune system's response to cancer. We look forward to exploring the potential of PS-targeting agents alone and with other immune modulators that may lead to novel advances in cancer therapy."

8-24-15: Peregrine & AstraZeneca & Peregrine Enter Collab. to run Ph1/Bavi+Durva/mult. solid tumors http://tinyurl.com/owlxpsf
...and then: 10-15-15: Peregrine & AstraZeneca Expand Collab. to run Ph2/Bavi+Durva/2L_NSCLS http://tinyurl.com/q79bkam

1-6-16: Peregrine enters into Research Collab. with NCCN http://tinyurl.com/zmxtpsb

1-11-16: Peregrine Plans Expansion of Bavi Clinical Pgm http://tinyurl.com/zhdy37a
...New Ph2/Bavi+Chemo/TNBC, which “originated from Peregrine's ongoing collab. W/MSKCC”. One site will be Providence CC/Portland w/P.I.=David Page.
Note1: ProvidenceCC was a SUNRISE site w/P.I.=Rachel Sanborn(Dir./Thoracic-Onology, Providence CC).
Note2: David Page worked & published w/J.Wolchok at MSKCC – ex: http://www.hemonc.theclinics.com/article/S0889-8588(14)00017-3/abstract

9-6-16: NCCN Awards 3 Bavi Trials, to begin "Early 2017" http://tinyurl.com/gutgwb5
...1: Ph1/Hepatocellular Cancer (Bavi+RAD+Sorafenib), MOFFITT CANCER CENTER, PI: Jessica Frakes, MD (Clinicaltrials has start=4-30-17)
...2: P1-2/Glioblastoma (Bavi+RAD+Merck’s Temodar), MASS-GEN. CC, PI: Elizabeth Gerstner, MD
...3: Ph2/Head+Neck (Bavi+Merck’s Keytruda), JOHN-HOPKINS(Sidney Kimmel CC), PI: Ranee Mehra, MD

10-10-16/ESMO’16: Sunrise Biomarker #1 (B2GPI) announced http://tinyurl.com/hp73njt
...”We are optimistic that addl. Biomarkers associated with improved outcomes for bavituximab-containing treatments will be identified as the analysis continues.”

12-7-16/IASLC’16/Vienna: Sunrise Biomarker #2 (Complement Act. & IL-10) revealed in abstracts, but withdrawn due to “data anal. not complete”(IR) http://tinyurl.com/z8cq8vx
...LEAD AUTHOR: David E. Gerber/UTSW, SENIOR AUTHOR: Rachael Sanborn/ProvidenceCC

12-12-17/CC/S.King: “We are currently evaluating addl. Biomarkers that we hope will allow us to identify a profile for patients who will receive therapeutic benefits from a bavituximab-containing treatment regimen.” http://tinyurl.com/hhn4gga

3-1-17/AACR’17: Sunrise Biomarker #3 (INF-y) revealed in abstracts http://tinyurl.com/zdsbds8
...LEAD AUTHOR: N.Kallinteris (PPHM), SENIOR AUTHOR: Rachael Sanborn/ProvidenceCC

= = = =MY OPINIONS:
1. In think the newly revealed 4-3-17 AACR’17 Biomarker #3 (IFN-y) supplants the previous two. I think they kept searching for better & better ones, and #3 is the latest & greatest. Thus, it’s THE ONE they chose to show off at AACR’17.

2. I think that Jedd Wolchok and his Lab are deeply involved with helping PPHM put together the final protocol’s for the 3 NCCN trials and the planned AZN “Mult. Tumor Types” trial. You see Providence CC’s Dr. Rachael Sanborn appear as Senior Author of the last 2 Biomarker Abstracts, with ties back to MSKCC/Wolchok thru Providence Co-Oncologist David Page, who prev. worked with Dr. Jedd at Mem.Sloan. PPHM+MSK+PROVIDENCE, tightly working together on future Bavi Trials.

3. No better evidence as to how close PPHM & Mem.Sloan/Wolchok have become than to look at AACR’17 (See http://tinyurl.com/zzldh9n ). The new (2nd) PPHM+MSK study revealed by the 3-1-17 abstracts is a complete mindblower (to me!):
#2. MSKCC+PPHM: 4-3-17 #1651, “PSTargeting+Adoptive TCell Transfer (ACT) Eliminates Adv. Tumors w/o Off-Target Toxicities, Melanoma” <=NEW(2nd) Joint MemSloan/PPHM study, see: http://tinyurl.com/h3ylrku




.
.
= = = = = = = = = = = = = = = = = = = =
Dr. Wolchok spoke about Bavi in the 11-14-16/PR (SITC’16, Joint MSKCC & PPHM Poster, “Phosphatidylserine Targeting Antibody in Combination with Checkpoint Blockade & Tumor Radiation Therapy Promotes Anti-Cancer Activity in Mouse Melanoma”)…
FULL SITC’16 ABSTRACT #199: http://bit.ly/2dHTEVn

11-14-16/JEDD WOLCHOK: "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." http://tinyurl.com/js3fca4

11-14-16/TAHA MERGHOUB (Co-Dir., MSK’s Ludwig Collab. Lab): "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

[Wernaaa]

Avid will be profitable in 11 months, Avid II, Avid III, further costreduction....

Lets also discuss this crap....!!!

[Globewriter]

An off target toxicity and Cytokine Storm message

I kept hearing about some storm of sorts that can build up and cause more havoc than one would want and going thru a separation then complete divorce can be presented as good if you are given the beach house and the spouse gets the beaten down house way out in the middle of no where

As for Avid Bioservices - the late Peregrine Pharmaceuticals that had MANY collaborations are a distant past thought with ex CEO Steve King not even around to concur with present Avid Bio BOD that companies like Humanigen were indeed one of the collaborations and should make any analyst start to wonder

You all like Mr Chappell at Humanigen and you all like Brian Sheehy ?

Imagine a month after a divorce and after the storm passes, skies clear and you sitting out looking at the ocean on that nice beachfront property as Ex partner has all types of visitors asking about paying multiples $$$ for the house in the middle of no where that somehow someone used special optics to determine the house sits on a gold reserve.

Sometimes it is best to ask the important questions before departing with any asset and ask for all who had access to that asset.

Humanigen Elects Dr. Dale Chappell to Board of Directors
February 08, 2021 07:00 AM Eastern Standard Time
BURLINGAME, Calif.--(BUSINESS WIRE)--Humanigen, Inc. (NASDAQ:HGEN) (“Humanigen”), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called cytokine storm with its lead drug candidate lenzilumab™, today announced that the Company’s Board of Directors (the “Board”) has elected Dr. Dale Chappell, the Company’s chief scientific officer, to serve as a director of the Company, effective February 5, 2021. Dr. Chappell will continue to serve as the Company’s chief scientific officer.