Third Quarter 2016 - - PowerPoint PPT Presentation
!"#$%&'() !"#$%&'() *+#,-."/.&%('+&.0)1 *+#,-."/.&%('+&.0)1 2-%34!.'+%3')42+3542%460042+37 Third Quarter 2016 !"#$%&##'()*+,&'-.%/&0&%1&'-+22 Peter Culpepper, MBA, CPA Chief
!"#$%&'() !"#$%&'() *+#,-."/.&%('+&.0)1 *+#,-."/.&%('+&.0)1 2-%34!.'+%3')42+3542%460042+37
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Peter Culpepper, MBA, CPA Chief Operating Officer, and Interim Chief Executive Officer
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Laura Panjwani @OncEditorLaura Published Online: Monday, Oct 31, 2016
James Allison, PhD
Web Exclusives >
James Allison Says Rational Combinations Key to Immunotherapy Success in "Cold" Tumors
Immunotherapy has been a game changer in oncology, improving survival and providing long, durable responses in melanoma, lung, head and neck cancer, and others. The success of immunotherapies in those cancers—which are likely seeing a better rate of response due to their high mutational burden—is now paving the way for what are known as “cold” tumors, those that don’t have a heavy mutational burden or significant T-cell infiltration, said James Allison, PhD. “There is enough progress being made across the board that I think we can start thinking about some of the colder tumors responding if we just keep studying and making rational combination decisions,” said Allison, professor and chair of Immunology at MD Anderson Cancer Center. “As we understand this better, we can rationally put two things together that won’t just duplicate or cancel each other out, but will do different things that can at least be additive, if not synergistic.”
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!! !! !! !! Combination Therapy with IL PV-10 and anti-CTLA-4 antibodies in B16-OVA bearing mice
10 20 30 40 50 60 70 PBS PV10 anti-CTLA4 PV10+anti-CTLA4 Mean Tumor Weight (mg) 200 400 600 800 1000 1200 1400 1600 PBS PV10 anti-CTLA4 PV10+anti-CTLA4 IFN-gamma (pg/ml) B16 MC38 p=0.05 Treatment with anti-CTLA-4 antibodies in combination with IL PV-10 leads to the induction of B16-specific T cells Treatment with anti-CTLA-4 antibodies in combination with IL PV-10 results in smaller B16-OVA tumors
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!! !! !! !! Combination Therapy with IL PV-10 and anti-PD-1 antibodies in B16-OVA bearing mice
Mean Tumor Size (mm2) 10 20 30 40 50 60 70 80 5 10 15 20 25 PBS PV10 anti-PD1 PV10+anti-PD1 Days p<0.05 500 1000 1500 2000 2500 3000 3500 PBS PV10 anti-PD1 PV10+anti-PD1 IFN-gamma (pg/ml) Treatment with anti-PD-1 antibodies in combination with IL PV-10 results in reduced growth of B16-OVA tumor Treatment with anti-PD-1 antibodies in combination with IL PV-10 leads to the induction of B16-OVA-specific T cells p<0.05
\_
!! !! !! !! Combination Therapy with IL PV-10 and anti-PD-L1 antibodies in B16 bearing mice
10 20 30 40 50 60 5 10 15 20 25 Days Mean Tumor size (mm2) PBS + NrIgG PBS + anti-PDL1 PV10 + NrIgG PV10 + anti-PDL1 p<0.05 500 1000 1500 2000 2500 PBS PV10 anti-PDL1 PV10+anti-PDL1 IFN-gamma (pg/ml)
* *
*p<0.05 compared to PV-10 treated mice
Treatment with anti-PD-L1 antibodies alone or in combination with PV-10 leads to the induction of B16-specific T cells Treatment with anti-PD-L1 antibodies in combination with IL PV-10 results in reduced growth of B16 tumor
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FH _
/ @#O'&<O(*%O.#)*1(+]#O(#5O0&(,'+(#$O7#/*.#O+%2$O%**O0&%# / G$O&O$'&00O*.1&(+]&%+*(O5#O&.#O$3$)#-%+70#O%*O,#&%"O7<O&O%"*3$&(,O)3%$ / @#O&.#O$3$)#-%+70#O%*O,+$.3-%+9#O)"&(1#O+(O'&(&1#'#(%ODf"*3$#O)0#&(+(1gEO%"&%O )*30,O&0%#.O)*3.$#O*/O%#)"(*0*1<O&(,h*.O)&-+%&0O$%.3)%3.# / @#O'&<O/&+0O%*O'&(&1#O%.&($+%+*(O%*O&O0&.1#.O*.1&(+]&%+*(OD1.*5%"O-.#)+-+%&%+(1O )*00&-$#E
FH c
/ @*.4O7<O"+1"Ij3&0+%<O%"+.,O-&.%+#$O)*(%+(3#$O%*O73+0,O).#,+7+0+%<O/*.O)*.#O+(,+)&%+*($O &(,O$3--*.%$O7.*&,Of'30%+I+(,+)&%+*(gO-.*'+$#O/*.OPRIFH / fV&$4#%O$%3,<gO,&%&O/.*'O*3.O"#-&%+)O%.+&0O+$O)0*$#0<O-&.&00#0+(1O5*.4O+(O%"#O0&7 / G$+&O-&%"O/*.5&.,O+$O)0#&.6O&(,O%"#O&,9&()#,O-&%"ODQI`EO)*30,O7#O&O1&'#O)"&(1#.O %"#.#O&(,O+(O%"#O@#$% / P"&$#OLO+(%#.+'O&$$#$$'#(%O&(,OP"&$#OF7O-.#0+'+(&.<O&$$#$$'#(%O5+00O*))3.O+/O5#O $%&<O%"#O)*3.$# / PRIFHO"&$O&O(*9#0OT*G +(O&O).*5,#,O/+#0,O"3(1.<O/*.O(*9#0%< / !"#O$&'#O)*30,O&--0<O%*OPYIFHt
FH d
/ !"#O0&%#$%O-#.+*,O*/O+..&%+*(&0O#837#.&()#O+(O*()*0*1<O$##'$O%*O7#O#(,+(1 / PRIFHO&,,.#$$#$O&(O*--*.%3(+%<O%*O73+0,O*(O)3..#(%OQI`O7&)47*(# / PRIFHO&--#&.$O%*Of'&4#O%"#O-&%+#(%2$O%3'*.O"+$O*.O"#.O/.+#(,g / PRIFHO)*30,O7#O&O7.#&4%".*31"O/*.O+''3(*0*1+)&00<Of)*0,gO%3'*.$ / PRIFHO)*30,O7#O&O)*'-#00+(1O9&03#O-.*-*$+%+*(O/*.O7+1O-"&.'& / PRIFHO)&(O7#O&O10*7&0O-0&<ODf+%O)&(O7#O"&30#,O+(O&O7&)4-&)4O%*O%"#O/&.%"#$%O.#&)"#$gE / PYIFHO'&<O/+%O'&(<O*/O%"#$#O-&.&'#%#.$O&$O5#00
FH e
/ `3.O$3--0<O)"&+(O+$O.*73$% / !"#O/+.$%O^KGO$%&7+0+%<O0*%O*/OPRIFHO"&$O7##(O'&(3/&)%3.#, / @#29#O+'-0#'#(%#,Oj3&0+%<O$<$%#'$O(#)#$$&.<O/*.O-"&$#OLO%#$%+(1 / @#29#O73+0%O&O10*7&0O)0+(+)&0O,#9#0*-'#(%O%#&' / @#29#O/*$%#.#,O)*.-*.&%#O)*00&7*.&%+*($O%*O$'**%"O10*7&0+]&%+*(O*/O-.*1.&'$
FF H
/ GO%<-+)&0O,.31O%&4#$O*9#.OFHO<#&.$O&(,OmN:\VO%*O,#9#0*- F / K#$-+%#O'+$$%#-$6O5#29#O$-#(%O&O%+(<O/.&)%+*(O*/O5"&%O+$O%<-+)&00<O.#j3+.#,O%*O7.+(1O&O (#5O,.31O%*O'&.4#%
)(I68$3@8M86(G%$'8623+(!"#$%&$'(,*+(,-)*
FF F
/ @#O"&9#O)*($+$%#(%0<O&,9&()#,O)0+(+)&0O,#9#0*-'#(%O*/OPRIFHO/.*'O+(+%+&0OQ^KO/+0+(1O +(ONHHZO%*O-"&$#OF6O-"&$#ONO&(,O(*5O-"&$#OL / @"+0#O5#O5#.#O)"&.%+(1O&O)*3.$#O/*.O'#0&(*'&O%".*31"O%"#O#(,O*/O%"#O%&.1#%#,O %"#.&-<O#.&O&(,O$%&.%O*/O%"#OQI`O#.&O5#O)*(%+(3#,O%*O&,9&()#O)0+(+)&0O3(,#.$%&(,+(1O 9+&O#8-&(,#,O&))#$$6OT*G6OrA!6O&(,O"#-&%+)O-.*1.&'$ / !"+$O#8-#.+#()#O-.*9+,#,O%"#O(#)#$$&.<O/*3(,&%+*(O/*.O&O,3&0O-&%"O/*.5&.,O+(O '#0&(*'&OD$+(10#O&1#(%O&(,O)*'7+(&%+*(EO%"&%O5#O&.#O&,9&()+(1O%*,&< / `3.O-.+'&.<OBPO+(O-"&$#OLODP>;EO+$O(*5O7#+(1O&,9&()#,O7<O+(,3$%.<O&$O%"#O-.#/#..#,O BPO/*.O*()*0*1<O$%3,+#$ / @#O.#'&+(O&%O%"#O/*.#/.*(%O*/O(*(I)3%&(#*3$O)0+(+)&0O,#9#0*-'#(%O/*.OQSO&1#(%$
FF N
/ ;%&70#O&%O.**'O%#'-#.&%3.# / ^*O7+*$&/#%<O.#$%.+)%+*($ / P.#,*'+(&(%0<O0*)&0O%*8+)+%< / C&-&70#O*/O"+1"O.#$-*($#O.&%# / `/%#(O5+%"O'+(+'&0O+(%#.9#(%+*( / A&-+,O.#,3)%+*(O+(O%3'*.O73.,#( / C&(O-.*,3)#O&O$<$%#'+)O+''3(#O#//#)%O / ;+(10#I&1#(%O*.O)*'7+(&%+*(O3$#
/ B'#.1+(1O,&%&O'&<O7#O).3)+&0O+(O,#'*($%.&%+(1O'&.4#%O(+)"#
FF L