Added PR Notes to AACR’17/#1651 PPHM+MSK “Bavi+ACT/CAR T”
4-3-17/8am #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS [Joint PPHM & Memorial Sloan Kettering] “Targeting Phosphatidylserine in Combination with Adoptive T Cell TransferEliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model”<=NEW(2nd) MSK STUDY => 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 [TCRs] or chimeric antigen receptors [CARs]. 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 blockade did 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. --------------------- FROM PPHM’s 4-3-17 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=1019762 …”Latest Findings from Ongoing Collaboration with Memorial Sloan Kettering (MSK) Support Potential Applications for Combining CAR T & Anti-PS in Treatment of Solid Tumors”… For this study, a team of MSK researchers led by cancer immunotherapy thought-leaders, Taha Merghoub, Ph.D. and Jedd D. Wolchok, M.D., Ph.D., evaluated and compared the anti-tumor activity and off-target toxicities of adoptive T cell transfer therapy in combination with either PS-targeting antibodies or anti-OX40 antibodies in mice with advanced melanomas. Whereas PS-targeting and anti-OX40 demonstrated comparable tumor regression when administered in combination with transferred adoptive T cells, only the PS-targeting combination achieved these results without any off-target toxicities. By contrast, the anti-OX40 treatment combination triggered off-target inflammatory destruction of healthy tissues. Additional study results demonstrated that the PS-targeting antibodies decreased tumor-induced immunosuppression as evidenced by a decrease in immunosuppressive regulatory T cells (Tregs) and M2 macrophages. This finding is consistent with Peregrine’s belief that bavituximab may modulate the immunosuppressive tumor microenvironment and enhance the activity of immunotherapy agents. Taha Merghoub, Ph.D., Co-Dir. of the Ludwig Collaborative Laboratory at MSK: “While adoptive T cell transfer remains one of the most exciting new approaches to treating cancer, to date the toxicity associated with the treatment has limited its potential. We are encouraged that these study results showed that the combination of anti-PS and adoptive T cell treatment led to enhanced anti-tumor effect without any evidence of additional off-target side effects. “We believe that these findings may support potential applications for this combination in solid tumors in the future.” Joseph Shan, Peregrine’s VP of Clinical & Regulatory Affairs: “These study results provide further support for our belief that anti-PS agents such as bavituximab can play an important role as part of combination cancer treatments. This is directly tied to the agents’ ability to modulate the tumor microenvironment to combat the immunosuppression that limits the activity of CAR T and immunotherapies. Importantly, we are now also seeing evidence that this targeted modulation of the tumor microenvironment by anti-PS allows for enhanced activity of these other treatments without triggering any off-target toxicities. This is opposed to other conventional immunotherapies such as anti-OX40 with systemic mechanisms of action. We believe this advantageous tolerability profile will be a key benefit in positioning anti-PS agents for inclusion in optimal combination cancer regimens.” --------------------- 8-2015: Presently there are 3 types of Adoptive Cell Transfer (ACT) using effector T cells that are advancing on a path towards regulatory approval: 1. TILs (tumor infiltrating lymphocytes) have been developed with slow but continuing progress over several decades. 2. CARs (chimeric antibody receptors) – newer gene-modified T cells strategy 3. TCRs (T-cell receptors) – newer gene-modified T cells strategy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507286/ ...“Adoptive T cell transfer is like ‘giving patients a living drug’,” states Renier J. Brentjens, MD/PhD, of Memorial Sloan Kettering Cancer Center (MSKCC). … https://www.cancer.gov/about-cancer/treatment/research/car-t-cells ...“Adoptive T cell therapy (ACT) is one stone in this new pillar, a potentially powerful approach to cancer treatment that relies on the infusion of tumor-specific T cells.” … https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327320 = = = = = = = = = Interesting 3-31-17 Sloan Kettering Tweet re: AACR’17 3-31-17 9:20amET “Getting ready for #AACR17? #Immunotherapy will be a hot topic. Learn more about how it works (video). @AACR” https://twitter.com/sloan_kettering Points to this 4-2016 Video (1:20): “Immunotherapy – How It Works”https://www.youtube.com/watch?v=COQ1AeoGyco Beg@:39: “Immunotherapy drugs release this brake and empower immune cells to fight the cancer. Sometimes the immune system needs a tune-up before it can fight cancer. Immune cells can be removed from the body, armed with new proteins that can target cancer cells, and given back to a patient in large numbers. Once inside the body, the modified immune cells recognize and attack the cancer. This approach is called CAR T cell therapy. [an Adoptive Cell Transfer “ACT” strategy] Despite the promise of immunotherapy, not everybody responds. MSKCC scientists are exploring ways to improve immunotherapy.” =============AND, THIS 3-23-17 PARKER FOUNDATION RELEASE ON AACR’17: 3-23-17: “Parker Institute for Cancer Immunotherapy Scientists to Present Research on Checkpoint Inhibitors, Adoptive Cell Therapy, and Other Advances in Immuno-oncology at AACR 2017” Investigators affiliated with the Parker Institute for Cancer Immunotherapy will present some of the most anticipated immuno-oncology research at the 2017 AACR Annual Meeting. The event takes place at the Walter E. Washington Convention Center in Washington, DC, April 1-5 2017. . . Other adoptive cell therapy abstracts of interest: • ”Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” [see http://tinyurl.com/nx5q5os ] The principal investigator is Taha Merghoub, PhD, Parker Institute member researcher at Memorial Sloan Kettering Cancer Center. Co-authors include Parker Institute Center Director Jedd Wolchok, MD, PhD, at Memorial Sloan Kettering Cancer Center. http://www.parkerici.org/media/2017/parker-institute-for-cancer-immunotherapy-scientists-to-present-research-on ----------ACT NOTES: 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: The Parker Foundation: “The Immunotherapy Dream Team” 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
WOW: 2 Stat. Sig. Improvements when Bavi added. “mOS was not reached” in both cases where the BAVI arm "received subsequent immunotherapy"...
FROM PPHM’s 4-4-17 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=1020046 …”SUNRISE Data Analysis Demonstrates Stat. Significant Overall Survival (OS) Improvement in Patients Receiving Bavituximab+Docetaxel and Subsequent Immunotherapy Compared to Placebo+Docetaxel and Subsequent Immunotherapy… AACR’17 presentation (#CT159/25) of results of a new analysis of the Phase III SUNRISE trial… Data demonstrated that for patients in the study's BAVI+DOCE treatment arm who received subsequent immunotherapy, the mOS was not reached, while mOS was 13.0mos. for patients in the study's DOCE+PLACEBO arm who received subsequent immunotherapy [HR=0.43; p=.005]. These are the first clinical results reported supporting the hypothesis that bavituximab may modulate the tumor microenvironment to enhance the anti-tumor activity of immunotherapy agents... The presentation highlighted an analysis in which the company evaluated the impact of subsequent immunotherapy treatment, as well as patients' pre-treatment interferon gamma (IFN-y) levels on overall survival. Overall, low peripheral IFN-y correlated with more favorable OS in the patients receiving BAVI+DOCE and is a biomarker of interest. Data were also analyzed by low versus high IFN-y levels. For patients with low pre-treatment IFN-y levels who received subsequent immunotherapy, those in the BAVI+DOCE arm did not reach mOS compared to mOS of 12.1mos. for the DOCE+PLACEBO arm [HR=0.24; p<.001]. Joseph Shan, Peregrine’s VP of Clinical & Regulatory Affairs: "We are extremely encouraged by the results of these exploratory analyses which provide further clinical rationale for combining bavituximab and checkpoint inhibitors. This will be the key focus for upcoming early phase clinical trials, which includes a study of bavituximab and pembrolizumab in head and neck cancer through our ongoing collaboration with the NCCN.” ...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. PS-targeting antibodies have demonstrated an ability to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses. Bavituximab is believed to override PS immunosuppressive signaling by blocking the engagement of PS with its receptors and sending an alternate immune activating signal.
Summary of the 3 known Ph3/Sunrise Biomarker Data Presentations:
#1 10-10-16/ESMO’16: “B2GPI Biomarker(30%pts) StatSig OS 7.7=>13.2mos.” David R. Spigel: LEAD AUTHOR: CSO/Dir. Lung Cancer Pgm/Sarah Cannon Res. David E. Gerber: SENIOR AUTHOR: UTSW/Dallas (Sunrise PI) CO-AUTHORS: R.Natale/CEDARS-SINAI, R.Sanborn/PROVCC, PPHM’s N.Kallinteris, J.Lai, M.Tang, J.Shan, and 7 Intl. Sunrise PI’s: Ger/2, Ukraine, Greece, Spain, Korea, Hungry. RESULTS: ~200 of 600 pts (~30%) tested positive for B2GPI(200-240). Those 200 received Stat.Sig. Improvement in O/S 7.7=>13.2mos; ie, lived +70% longer. MORE DETAILS: http://tinyurl.com/hp73njt
#2 12-7-16/WCLC’16(IASLC): “Complement & IL-10 Pathways Id Pts Benefiting from Bavi+Doce” PRESENTATION CANCELLED – IR said,”Data analysis not completed in time.” David E. Gerber: LEAD AUTHOR: UTSW/Dallas (Sunrise PI) Rachael Sanborn: SENIOR AUTHOR: Dir./Thoracic-Oncology, Providence CC/Portland CO-AUTHORS: L.Horn/VANDY, G.Losonczy/BUDAPEST, R.Natale/CEDARS-SINAI, H.Roder, J.Roder/BIODESIX, PPHM’s N.Kallinteris, M.Tang, J.Shan. RESULTS: 104 of 193 pts tested high for complement activation, and from that, a 2nd subgrp isolated that tested low IL-10: O/S 5.9=>12.5mos. Remaining 397pts will be presented at WCLC’16. * ”The Complement System is an enzyme cascade that is a collection of blood & cell surface proteins to help the abilities of antibodies to clear pathogens from an organism.” * ”IL-10 is an anti-inflammatory TH2 cytokine that has a critical role in limiting the immune response to pathogens to prevent host damage.” MORE DETAILS: http://tinyurl.com/z8cq8vx . . . . 12-12-16 CEO/S.King: “We are actively evaluating addl. potential biomarkers and we hope to identify a profile for patients who will receive therapeutic benefit from treatment with bavituximab.” VP/JOE SHAN: ”Numerous addl. biomarkers are currently being evaluated.”http://tinyurl.com/hhn4gga
#3 4/3/17 AACR’17 CT159/25 (Session: Phase II/III Clinical Trials in Progress) “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” Lead Author: Nikoletta Kallinteris (PPHM); Senior Author: Rachael Sanborn (Dir./Thoracic-Oncology, Providence CC); CO-AUTHORS: L.Horn/VANDY, T.Guennel/PRECISION-FOR-MEDICINE, PPHM’s N.Kallinteris, M.Tang, S.Yin, J.Lai, J.Shan. NOTE: “IFNy, or type II interferon gamma, is a cytokine that is critical for innate & adaptive immunity against viral, some bacterial & protozoal infections.” 4-4-17/PR: ( http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=1020046 ) “SUNRISE Data Analysis Demonstrates Stat. Significant Overall Survival (OS) Improvement in Patients Receiving Bavituximab+Docetaxel and Subsequent Immunotherapy Compared to Placebo+Docetaxel and Subsequent Immunotherapy…” Pts in the study's BAVI+DOCE arm who received subsequent immunotherapy, the mOS was not reached, while mOS was 13.0mos. for patients in the study's DOCE+PLACEBO arm who received subsequent immunotherapy [HR=0.43; p=.005]. These are the first clinical results reported supporting the hypothesis that bavituximab may modulate the tumor microenvironment to enhance the anti-tumor activity of immunotherapy agents... The presentation highlighted an analysis in which the company evaluated the impact of subsequent immunotherapy treatment, as well as patients' pre-treatment interferon gamma (IFN-y) levels on overall survival. Overall, low peripheral IFN-y correlated with more favorable OS in the patients receiving BAVI+DOCE and is a biomarker of interest. Data were also analyzed by low vs. high IFN-y levels. For patients with low pre-treatment IFN-y levels who received subsequent immunotherapy, those in the BAVI+DOCE arm did not reach mOS compared to mOS of 12.1mos. for the DOCE+PLACEBO arm [HR=0.24; p<.001]. Joseph Shan, Peregrine’s VP of Clinical & Regulatory Affairs (4-4-17/PR): "We are extremely encouraged by the results of these exploratory analyses which provide further clinical rationale for combining bavituximab and checkpoint inhibitors. This will be the key focus for upcoming early phase clinical trials, which includes a study of bavituximab & pembrolizumab in Head & Neck cancer through our ongoing collaboration with the NCCN.” --------- **NOTE: Per JDM find, we know that 96 Sunrise Pts received “Subsequent Immunotherapy” - see 10-13-16 ASM CEO S.King Slide#14: http://tinyurl.com/n2bajew ----------- 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, Dir./Thoracic-Oncology http://cancergrace.org/faculty/rachel-sanborn-md - Dr. Sanborn's Conflicts of interest: DNA, AZN] 1=Peregrine Pharmaceuticals 2=Vanderbilt-Ingram Cancer Center, Nashville, TN 3=Precision for Medicine, Frederick, MD 4=Providence Cancer Center, Portland, OR ORIG. AACR’17 ABSTRACT: BACKGROUND: SUNRISE, a global, double-bind, Phase III trial of docetaxel (D) plus bavituximab (B) or D plus placebo (P) in previously treated non-squamous non-small cell lung cancer (NSCLC), demonstrated similar overall survival (OS) in both treatment arms. Immune correlate analyses including pre-treatment IFN-y levels in blood and tumor tissue were used to potentially identify prognostic and/or predictive correlation with clinical outcome. METHODS: Serum was isolated from all randomized NSCLC patients at screening, periodically during treatment and at disease progression for evaluation of IFN-y levels using the Simoa TM assay (Myriad RBM, Austin, TX). Available archival tissue was also tested for 91- immune gene activation markers, including IFN-y by the Fluidigm-based gene-expression platform (Sirona Dx, Lake Oswego, OR). Kaplan-Meier statistical methods and Cox proportion hazards models were utilized to evaluate and contrast the correlation of peripheral and intratumoral IFN-y levels with OS. Patients were classified paradoxically as IFN-y "low" with a favorable disease prognosis vs. "high" associated with more aggressive disease based on the median. RESULTS: Pretreatment serum results were available for 582 out of the 597 randomized patients. Each patient was classified to be pre-treatment IFN-y high or low (< cut-off) using cut-off 0.093 pg/ml, which is the median IFN-y value in the D+B group. Median overall survival (mOS) in all patients with IFN-y low is 11.3mos. (95% CI, 10.1-13.5) vs. 10.4mos. (95% CI, 8.4-11.3) in all IFN-y high; p=0.047. mOS of D+B arm is 11.6mos. (95% CI, 10.2-13.9) and 11.1mos. (95% CI, 9.1-14.7) in the D group; p=0.982 for IFN-y low. mOS of D+B arm is 9.0mos. (95% CI, 6.7-11.2) and 10.6mos. (95% CI, 8.9-13.0) in the D group; p=0.252 for IFN-y high. With the limited intratumoral IFN-y gene expression data (n=33), no statistically significant correlation with OS was observed. CONCLUSIONS: Correlative approaches identified low peripheral low IFN-y at pretreatment as a biomarker of interest correlating with more favorable clinical outcomes and is consistent with the hypothesis that bavituximab may demonstrate more immunomodulatory effects in patients with “immune cold” tumors. POSTER #159/25 IMAGE: http://www.peregrineinc.com/images/stories/pdfs/aacr2017kallinteris.pdf
= = = = = = = =BIOMARKER #3 (IFN-y) AND PPHM/NCCN JOHNS-HOPKINS TRIAL TIE-IN (???): Dr. Ranee Mehra’s (Johns-Hopkins/SidneyKimmelCC) work with Biomarker IFN-y seems to dovetail into PPHM’s newly revealed Sunrise Biomarker #3 that was presented 4-3-17 at AACR’17: #CT159/25, “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” ------- 1-6-17 Dr. Ranee Mehra (Johns-Hopkins/SidneyKimmelCC), P.I. for the upcoming NCCN Ph2 Bavi+Keytruda Head&Neck trial. Excerpts from her 1-6-17 talk at GBMC/Greater Balt. MC “H+N Grand Rounds”… I do believe she views this trial is an important part of Johns-Hopkins future anti-cancer direction. Also, look at her Slide #36: “Interferon-y Signature”. Is that an exact tie-in to the newly-revealed AACR’17(4-3-17) Sunrise Biomarker #3 Abstract, “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” (embargoed)? I still totally believe that PPHM has been working with the 3 NCCN Bavi Awardees (Moffitt, MassGEN, JohnsHopkins) to weave in the “chosen” Sunrise Biomarker that is associated with generating “improved outcomes for bavituximab-containing treatments” in future trials. PDF Link(1-6-17): http://www.gbmc.org/workfiles/HeadNeck/Grand%20Rounds/IO_Therapy_SCCHN02017.pdf ------- Note: DR. RANEE MEHRA was co-author of ASCO’16, “Biomarkers & Response to Pembro(Keytruda) in Recurrent/Metastatic Head & Neck Cancer” - Conclusion: “The IFN-y signature score was significantly associated with ORR, PFS, and OS (all, P< .001)… PD-L2 & IFN-y signature may be associated with clinical response to Pembro[Keytruda] and may offer addl. strategies to improve prediction of response.” http://meetinglibrary.asco.org/content/165708-176
PPHM’s NCCN#3: Ph2/Progressive Squamous Head+Neck (Bavi+Merck’s Keytruda), JOHNS-HOPKINS(Sidney Kimmel CC) - PI: Ranee Mehra, MD ”Phase II Study of Pembrolizumab[Keytruda] & Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head & Neck"http://tinyurl.com/gutgwb5 Ranee Mehra, MD: Dir., Head & Neck Oncology Therapeutics, Johns Hopkins Medicine https://www.linkedin.com/in/ranee-mehra-34a0467 RANEE MEHRA Disclosures(ASCO’16): GSK, Bayer, BMS, Genentech, Novartis, Mirati Ther.
NCCN Bavituximab Trials Announced 9-6-16 - To Begin "Early 2017"http://tinyurl.com/gutgwb5 ...#1: Ph1/HepC-Related Hepatocellular(Liver) (Bavi+RAD+Sorafenib), MOFFITT CANCER CENTER - PI: Jessica Frakes, MD - https://clinicaltrials.gov/ct2/show/NCT02989870 ...#2: P1-2/Newly Diag. Glioblastoma (Bavi+RAD+Merck’s Temodar), MASS-GEN. CANCER CENTER - PI: Elizabeth Gerstner, MD ...#3: Ph2/Progressive Squamous Head+Neck (Bavi+Merck’s Keytruda), JOHNS-HOPKINS(Sidney Kimmel CC) - PI: Ranee Mehra, MD
9-9-16/CC/JoeShan: “The 3rd award is for a Phase II study of pembrolizumab [Merck’s Keytruda, anti-PD-1] & bavituximab in Head & Neck Cancer. We are particularly excited about this project, as it will be the 1st clinical trial of bavituximab with a checkpoint inhibitor. In multiple previous preclin. studies, we have observed bavituximab's potential to work synergistically with PD1 inhibitors such as pembrolizumab (Merck’s Keytruda).” http://tinyurl.com/ktrfswj - - - - - - - - - - Steve King 9-9-16/CC: “Our collaboration with the NCCN has been an important part of our strategy for advancing the bavituximab clinical program in a cost effective way. We earlier provided NCCN with a $2mm grant to support bavituximab related clinical research with no further financial obligations, and these grant awards represent the outcome of a competitive selection process for the best proposals. These studies will evaluate novel bavituximab combinations in Glioblastoma, Head & Neck Cancer, and Hepatocellular Carcinoma, including an immunotherapy combination [Bavi + Merck’s Keytruda], which is a major focus for advancing the program.” http://tinyurl.com/ktrfswj - - - - - - - - - - Steve King 9-9-16/CC/Q&A: “I’m very excited about the combinations that were chosen because the Radiation combination is one that in preclinical studies, as was mentioned during the prepared remarks, has always shown a lot of promise. It’s great to be able to now see that put into a clinical setting in a couple of different clinical trials. And the I-O combinations, as Jeff mentioned during his prepared remarks, is a major focus of ours. So to see a Pembro [Merck’s Keytruda] combination picked as well, we are just really excited that these were the 3 winners out of the NCCN selection process.” http://tinyurl.com/ktrfswj
#1 10-10-16/ESMO’16: “B2GPI Biomarker(30%pts) StatSig OS 7.7=>13.2mos.” http://tinyurl.com/hp73njt 10-10-16/PR: “Peregrine Reports Top-Line and Initial Biomarker Data from Phase III SUNRISE Trial of Bavituximab in Oral Presentation at Eur. Society for Medical Oncology (ESMO) 2016 Congress” -- Company Has Identified Beta-2 Glycoprotein-1 (B2GP1) as a Biomarker that Correlates with Statistically Significant Improvement in Overall Survival for Patients Receiving the Bavituximab Combination Compared to Chemotherapy Alone -- Ongoing SUNRISE Trial Biomarker Analysis Expected to Identify Addl. Biomarkers Associated with Patients Benefiting from Bavituximab Treatment that Will Help Guide Program's Future Clinical Development. . . ** "With every clinical trial we conduct, we are constantly reminded of the difficulty involved in treating patients with NSCLC. This continues to prove to be a very challenging cancer to combat and the need for effective treatments remains high," David R. Spigel, MD, CSO and PgmDir. of Lung Cancer Res. at the Sarah Cannon Res. Inst. and one of the lead investigators in the SUNRISE trial. "The findings with regard to B2GP1 that have been collected as part of the ongoing SUNRISE trial data analysis are interesting and support further investigation." ** Peregrine intends to further evaluate the role of B2GP1 levels in response to bavituximab therapy in future clinical trials. The company has filed a new patent application directed to the use of this initial biomarker discovery. Addl. patient sample testing & analysis is ongoing and may result in other biomarkers of importance. -------------- ** Data presented at ESMO’16 demonstrated that patients with pre-treatment B2GP1 levels between 200 and 240 (representing approx. 30% of randomized patients) achieved a statistically significant, 5.5-mo. improvement (13.2 mos. vs. 7.7 mos.) in MOS as compared to patients in the ctl. group with the same range of B2GP1 levels [p = 0.049; HR=.67]. ------------- ** "We would once again like to thank all of the patients, clinical investigators and scientists who participated in the SUNRISE trial and have made it possible for us to continue to collect and analyze a range of key data from the study. While we were disappointed with the trial being discontinued earlier in the year, we are excited by the fact that we are beginning to learn important information from the trial through the ongoing biomarker analysis program that will be critical in helping guide the future clinical development of bavituximab," said Joseph Shan, VP/Clin&Reg.Affairs at Peregrine. "It is encouraging that the initial biomarker analysis has identified an important biomarker early in the process and we are optimistic that additional biomarkers associated with improved outcomes for bavituximab-containing treatments will be identified as the analysis continues. We expect to be able to share the emerging data over the coming months at scientific & medical conferences as the more results become available.” http://investorshub.advfn.com/boards/read_msg.aspx?message_id=125687447
= = = = = = = = = = = = = = = = #2 12-7-16/WCLC’16(IASLC): “Complement & IL-10 Pathways Id Pts Benefitting from Bavi+Doce” <=CANCELLED/”Anal.Not.Done(IR)” ...Lead author (presenter) is UTSW’s Dr. David Gerber (previously presented Ph2/NSCLC data and Prelim. SUNRISE data at AACR’14). The Senior author is Dr. Rachel E. Sanborn, Co-Dir., Thoracic Oncology Pgm, Robert W. Franz Cancer Res. Center, Earle A. Chiles Res. Inst., Providence CC, Portland, OR. Interestingly, one co-author is Heinrich Roder, CTO of Biodesix, Boulder CO... ABSTRACT CONCLUSION: “...Proteomic & correlative approaches identified complement activation and low IL-10 levels as important pathways for predicting improved outcomes of patient treatment with Doce+Bavi, in line with preclinical work on Bavi’s MOA...” [Pts=193, within the 1st subgroup of N=104, a 2nd subgroup isolated: MOS 5.9mos => 12.5mos.] Dec4-7 2016: “WCLC’16 - IASLC’s 17th World Conf. on Lung Cancer”, Vienna, Austria http://wclc2016.iaslc.org Pgm: http://wclc2016.iaslc.org/wp-content/uploads/2016/10/WCLC-2016-Poster-Program.pdf Poster Session with Presenters Present (ID 472) - Track: Advanced NSCLC 12/7/16 2:30-3:45pm David E. Gerber [UTSW], J. Roder, N.L. Kallinteris, L. Horn, G. Losonczy, R. Natale, M. Tang, Heinrich Roder [CTO, Biodesixhttp://www.biodesix.com/project/heinrichroder ], Joe S. Shan [VP/Clin+Reg], Rachel E. Sanborn [Providence Portland Medical Ctr] ”A Pre-Treatment Serum Test Based on Complement & IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel” ABSTRACT Book PDF: http://wclc2016.iaslc.org/wp-content/uploads/2016/12/WCLC2016-Abstract-Book_vF-WEB_revDec12.pdf ABSTRACT: http://library.iaslc.org/virtual-library-search?product_id=6 BACKGROUND: SUNRISE, a global, double-bind, Phase III trial of docetaxel (D) plus bavituximab (B) or D plus placebo (P) in previously treated non-squamous non-small cell lung cancer, demonstrated similar overall survival (OS) in both treatment arms. Mass spectrometry and correlative analysis were used to create a test able to identify a subgroup of patients benefitting from the addition of B to D. METHODS: Pre-treatment serum samples were available for 197 of the first 200 subjects enrolled in the trial. Mass spectra could be generated for 193 samples using the Deep MALDI method (Duncan et al, ASMS 2013), processed and features (peaks) identified. Mass spectral (MS) features associated with various biological functions were identified using a gene set enrichment analysis approach. Analysis of scores based on these MS feature, subsets indicated that in patients with High Complement Activation outcome depended on IL-10 activation in D+B but not in D+P. A test using the MS features associated with these functions was created to reliably identify a patient subgroup associated with clinical benefit using modern machine learning methods. RESULTS: Complement activation, as assessed by a classifier trained using related MS features, was a prognostic factor in both treatment arms, with high activation associated with poorer clinical outcome (OS HR = 0.54, log-rank p = 0.013 for D+B; OS HR = 0.60, log-rank p = 0.040 for D+P). Within the subgroup with high complement activation [N=50 (D+B); N=54 (D+P)], a second classifier using features related to IL-10 activation was able to isolate a subgroup of patients showing numerical benefit from the addition of B [Bavituximab] [median OS 5.9mos.(D+Placebo), 12.5mos.(D+Bavituximab)]. The remaining subgroup showed no benefit from addition of B [MOS 10.4mos.(D+P), 5.6mos.(D+B)]. Blinded validation of the test in the remainder 397 patients randomized in SUNRISE is will be presented. CONCLUSION: Proteomic and correlative approaches identified complement activation and low IL-10 levels as important pathways for predicting improved outcomes of patient treatment with D+B, in line with preclinical work on B’s mechanism of action. The test resulting from this work will undergo blinded indep. validation. - - - - - - - - - 12-20-16/S.Diaz(per Cheynew post #282068): “There was no poster in Vienna. The team was working on a very tight timeframe and, despite their best efforts, couldn’t complete the data analysis in time. Given the crunch, we knew there was a possibility that we wouldn’t meet the timing, so we never issued a PR announcing that we would present. Hence no PR announcing that we did not present.” S.DIAZ/FOLLOWUP: ”Unfortunately, I don’t have a timeline for completion of the analysis or where/when it might be presented. We’ll certainly announce this as soon as we know for sure. Only Joe Shan attended the conference for Peregrine.”
= = = = = = = = = =NOTE: Ann Oncol (11-8-16/suppl8): ESMO Symposium on Immuno-Oncology, Nov4-6 2016, Lausanne, Switzerland #30P: “Proteomic Signature Analysis & Application in Clinical Development of the Novel Phosphatidylserine-Targeting Immunotherapy, Bavituximab” http://annonc.oxfordjournals.org/content/27/suppl_8/mdw525.30 David E. Gerber [UTSW] 1, N.L. Kallinteris 2, L. Horn 3, G. Losonczy 4, R. Natale 5, Heinrich Roder 6 [CTO, Biodesix], M. Tang 7, J. Lai 2, J. Shan 8, Rachel E. Sanborn [9=Providence Portland Medical Ctr] 1 Oncology, UTSW-MC/Dallas 2 Clinical, Peregrine Pharmaceuticals Inc. 3 Oncology, Vanderbilt Ingram CC, Nashville, TN 4 Oncology, Semmelweis Univ., Budapest, Hungary 5 Oncology, Cedars-Sinai M/C, Los Angeles 6 Biodesix, Boulder, CO [CTO, Dr. Heinrich Roder: http://www.biodesix.com/project/heinrichroder ] “Founded in 2005, Biodesix discovers & commercializes cancer tests (diagnostics) that help patients & their doctors make more informed decisions about treatment based on a patient’s unique molecular profile.” 7 Biostatistics, Peregrine Pharmaceuticals Inc. 8 Clinical & Regulatory Affairs, Peregrine Pharmaceuticals, Inc. 9 Thoracic Oncology, Providence Cancer Care, Providence, OR Aim/Background: Understanding the multi-dimensional characteristics of cancer is essential to patient selection and treatment planning. Topline results from SUNRISE, a global double-blind Phase III trial of docetaxel + bavituximab (D+B) vs. docetaxel + placebo (D) in previously treated non-squamous NSCLC demonstrated mOS of 10.7mos. in the D+B group and 10.8mos. for the D group, which was unexpectedly different from the assumed 9.1mos. for D+B vs. 7.0mos. used for study powering. VeriStrat, a….[must subscribe] - - - - - - - - - - 5-31-14 ASCO’14: David Gerber/Joe Shan Poster on Ph3/SUNRISE Trial (#TPS8129) http://tinyurl.com/nv4jloo
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