1
TNBC (n=74) HR+ (n=205) Inferred activity Significance [-log 10 (p)] p=0.05 Inferred activity G1-2 (n=117) G3 (n=162) Significance [-log 10 (p)] Significance !"#$% &' ()*+ !"#$%&' (%)*+ ,- /0#01/ p=0.05 p=0.05 Correlation [Spearman Rho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`X. <71-$#$%/26 <-/#/))0"\8/T2.0/1a1 S7.DG.%6 b2.M78]6 @ 92)7.1M281 $` b]82?$#$%] 78H cD0121./?06 \8/T2.0/1] R$0)/17# L.#78%286 b2.M78]6 E bAb U2027.?- bMDR6 Z2G"_028DG.%6 b2.M78]6 I _801/1G12 $` <71-$#$%]6 \8/T2.0/1] R$0)/17#6 R2/H2#D2.%6 b2.M78]6 K Z71/$87# ,2812. `$. QGM$. 9/0270206 9B>d6 R2/H2#D2.% \8/T2.0/1] R$0)/17#6 b2.M78]6 N 92)7.1M281 $` b]82?$#$%] 78H cD0121./?06 \8/T2.0/1] R$0)/17#6 UCQR =7?-286 b2.M78]6 O A.2701 ,78?2. ,2812.6 L#/07D21-"B.78:28-7G0 B7002#6 b2.M78]6 P 92)7.1M281 $` b]82?$#$%] 78H cD0121./?06 4787 B#/8/:GM c``28D7?-6 b2.M78]6 &' B#/8/: `X. >.7G28-2/#:G8H2 G8H b2DG.10-/#`26 \8/T2.0/1a10:#/8/:GM >.78:`G.16 b2.M78]6 && 9/T/0/$8 $` b]82?$)71-$#$%]6 _801/1G12 `$. <71-$#$%]6 \8/T2.0/1] R$0)/17# R2/H2#D2.%6 b2.M78]6 &; B#/8/:28 H2. 417H1 BV#8 bMDR6 b2.M78]6 @ \8/T2.0/1a10:#/8/:GM 4?-#20J/%"R$#012/86 B#/8/: `X. b]8a:$#$%/2 G8H b2DG.10-/#`26 B/2#6 b2.M78]6 &E S7MM75281.GM R7MDG.%6 R$0)/17# F2.G07#2M6 R7MDG.%6 b2.M78]6 &I _801/1G12 $` <71-$#$%]6 <71-$#$%/2 Z$.H-200286 B7002#6 b2.M78]6 &K 92)7.1M281 $` b]82?$#$%] 78H cD0121./?06 \8/T2.0/1a10:#/8/:GM R7MDG.%"L))28H$.`6 b2.M78]6 &N 92)7.1M281 $` b]82?$#$%] 78H cD0121./?06 \8/T2.0/1] R$0)/17# S788-2/M6 b2.M78]6 &O R2#/$0 B#/8/:GM A2.#/8"AG?-6 A2.#/86 b2.M78] _MMG8$0G.T2/##78?2 0G)).200/$86 2T70/$86 $. 7T$/H78?26 -70 2M2.%2H 70 7 :2] 17.%217D#2 -7##M7.: $` ?78?2.6 H./T28 D] 2e%e ?-2?:)$/81 2f).200/$86 Q"?2## 2f-7G01/$86 78H /MMG8$0G)).200/T2 1GM$. M/?.$28T/.$8M281 (QSL*e S78] $` 1-202 ).$?20020 %282.712 H2`/82H ?$MD/871/$80 $` /MMG82" ?2## /8`/#1.7120 71 1-2 1GM$. 0/126 J-/?- ?78 D2 H212?12H D] /MMG8$-/01$?-2M/01.] (_R,*6 ,]Qc>6 $. M$.2 .2?281#] ?78 D2 /8`2..2H `.$M %282"2f).200/$8 H2?$8T$#G1/$8e C-/#2 0/%8/`/?781 J$.: -70 D228 H$82 1$ 01GH] %282 0/%871G.20 /8 1-2 QSL6 1-2 ?#/8/?7# .2#2T78?2 $` 0G?- /MMG82"?2## %282 0/%871G.2 $8 1-2.7)] -70 8$1 D228 01GH/2H 1$ 7 %.271 2f1281e C5 %&B5/0%'#05 0;5 ;:460;5/%/ 0;#0 0;5 %&$%B%$1#9 4#005"&/ 67 %881&5)3599 /%'&#01"5/ $505"8%&5 0;5 39%&%3#9 =5;#B%6" 67 ?@D %& 4#"0%319#" "5/46&/5 06 &56#$E1B#&0 3;5860;5"#4:F Q-/0 ).2028171/$8 /0 1-2 /812##2?1G7# ).$)2.1] $` 1-2 7G1-$.g).202812.e ,$817?1 1-2M 71 ?-./01$)-2.e0521$h/MMG8/1]D/$e?$M `$. )2.M/00/$8 1$ .2)./81 78Hg$. H/01./DG12e G*)HI)IJ <.202812H 71i 478 =81$8/$ A.2701 ,78?2. 4]M)$0/GMj6 92?2MD2. &'"&E6 ;'&P ?#3<'"61&$ -5/190/ C2 )2.`$.M2H 7 .21.$0)2?1/T2").$0)2?1/T2 787#]0/0 $` 7 0GD021 $` 1-2 RLU;"82%71/T2 0GD)$)G#71/$8 J/1-/8 1-2 b2)7.42)1$ 01GH] (Z,Q'&IO@E;K* /8 J-/?- J$M28 J/1- )./M7.] /8T70/T2 A, J2.2 .78H$M/52H 1$ 2/1-2. 87D")7?#/17f2# $. 0$#T281"D702H )7?#/17f2# `$##$J2H D] L, !&+e ;NP RLU;"82%71/T2 )71/2810 J/1- 0G``/?/281 kG7#/1] 07M)#2 .2M7/8/8% 1$ )2.`$.M J-$#2"1.780?./)1$M2 UZ=02k (l;''f&' K .27H0 )2. 1GM$.*e _MMG82 7?1/T/1] /8 1-2 QSL J70 /8`2..2H D] ?$M)7./8% 2f).200/$8 $` ;@ /MMG82"?2##"0)2?/`/? %282 0/%871G.20 H2./T2H D] A/8H27 21 7#e !;+ 1$ 1-$02 `.$M 7 D7?:%.$G8H )$)G#71/$8 $` &EKN 0/M/#7.#]").$`/#2H G802#2?12H 1GM$. 07M)#20 `.$M 1-2 Z781cM/?0 H717D702e K%'1"5 HF -LM)/5N =#/5$ %881&5 $536&B6910%6& &e \81?-6 S/?-72#6 21 7#e Z7D")7?#/17f2# T2.0G0 0$#T281"D702H )7?#/17f2# /8 82$7H[GT781 ?-2M$1-2.7)] `$. 27.#] D.2701 ?78?2. (b2)7.42)1$"bAb KP*i 7 .78H$M/02H6 )-702 @ 1./7#e !"#$%& (#$)* ;'&Km&Ni@EI"IK;e ;e A/8H27 b6 S#2?8/: A6 Q$0$#/8/ S6 21 7#i 4)71/$12M)$.7# H]87M/?0 $` /81.71GM$.7# /MMG82 ?2##0 .2T27# 1-2 /MMG82 #78H0?7)2 /8 -GM78 ?78?2.e +,,-#.&/ ;'&@m@Pi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log2(TPM+1) =* Lf).200/$8 $` &'E %2820 0)2?/`/? 1$ /MMG82 ?2## 0GD)$)G#71/$80 J2.2 G02H 1$ ?.2712 .2`2.28?2 %282021 H/01./DG1/$80 70 /8 A*e ,* _8`2..2H 7?1/T/1] (d"0?$.20* /8 n&;'' G80228 ?#/8/?7# ?7020e 4/%8/`/?781#] H/``2.281/7# 7?1/T/1/20 D21J228 D.2701 78H $1-2. 1])20 M7.:2H J/1- o 78H H/.2?1/$8 $` 01.$8%2. 700$?/71/$8 /8H/?712H /8 ?$#$.e =* ,#G012.2H /MMG82 7?1/T/1] 0?$.20 `$. ;NP b2)7.42)1$ )71/2810e A* <.$)$.1/$80 $` b2)7.42)1$ )71/2810 1-71 J2.2 ?$80/H2.2H -/%- (n&0H `.$M M278*6 8$.M7# (J/1-/8 &0H $` M278*6 78H #$J (p"&0H `.$M M278* `$. /MMG82 0GD02106 ?$M)7.2H 1$ .2`2.28?2 D.2701 ?78?2. 07M)#20e ,$#H C7.M R$1 Inferred activity score @6"5 =%64/: >=576"5 /01$: 5&0":A M"8 M M"8 ? - P1"'5": HQH HR S55</ HR S55</ <7?#/17f2# O' M%gM ; J22:#] Z7D")7?#/17f2# &I' M%gM ; J22:#] Q-2 H$02 J70 .2HG?2H 1$ &;I M%gM ; 7`12. .2?.G/1M281 $` EKE )71/2810 L)/.GD/?/8 P' M%gM ; ,]?#$)-$0)-7M/H2 K'' M%gM ; !54#"P5406 0"%#9 $5/%'& 67 ,T-R)&5'#0%B5 /500%&'Q M ? P01$: U5/%'& K%'1"5 VF W881&5 46419#0%6&/ 5&"%3;5$ S%0;%& 39%&%3#9 36B#"%#05/ =?1/T/1/20 (7D$T2* 78H 0/%8/`/?78?2 (D2#$J* `$. .2?2)1$. 0171G0 (=*6 %.7H2 (A* 78H 1-2 7%%.200/T28200 M7.:2. B/KN (,*e ^/820 H28$1/8% &0H 0-$J8 J-2.2 7T7/#7D#2e _8 0/%8/`/?78?2 )#$106 ?$#$. /8H/?7120 01.28%1- 78H H/.2?1/$8 $` 700$?/71/$8e 4/%8/`/?78?2 )"T7#G20 J2.2 #/M/12H 1$ 'e'''&e M ? K%'1"5 JF K699%319#" ;5945" 3599/ >XK,A #"5 #//63%#05$ S%0; $%775"5&0%#9 /1"B%B#9 =* Q>R 0?$.2 J70 0/%8/`/?781#] ).2H/?1/T2 $8 )7?#/17f2#"D702H Qf `$. c46 9>46 78H ),U /8 MG#1/T7./712 M$H2#0 A* S$07/? )#$1 0-$J/8% 28./?-M281 $` -/%- Q>R 0?$.2 J/1-/8 )71/2810 1-71 -7H ),U ()q'e''&;*e Model Endpoint odd ratio/hazard ratio (95 CI) p-value Cox OS 0.55 (0.39-0.77) 0.0005 Cox DFS 0.62 (0.47-0.81) 0.0004 Logistic regression pCR 1.63 (1.12-2.36) 0.0107 M ? I m m u n i t y B i o C;695)0"#&/3"%40685 /5N15&3%&' %& ="5#/0 3#&35" KKGT 36"5 =%64/%5/ 7"68 39%&%3#9 36;6"0/ 3#& =5 1/5$ 06 %$5&0%7: %881&5)3599 /%'&#01"5/F P453%7%3#99:D #$#40%B5 %881&%0: 0;"61'; L( "#0;5" 0;#& X)3599 "5/46&/5 #445#"/ 4"5B#95&0 %& ;%';)"%/< XL?@F X;5 4#005"&/ 67 0;5/5 %881&5 /%'&#01"5/D %& 4#"0%319#" 0;5 4"5/5&35 67 X 7699%319#" ;5945" 3599/D "579530 0;5 39%&%3#9 =5;#B%6" 67 ="5#/0 3#&35" #&$ 8%';0 =5 1/5$ 06 %$5&0%7: 0186"/ S%0; #& %&3"5#/5$ "5/46&/5 "#05 06 &56#$E1B#&0 3;5860;5"#4:F -575"5&35/ r Z71G.7# :/##2. (ZB* ?2##0 (N&s*6 78H .2%G#71$.] Q"?2##0 (N's* J2.2 `$G8H 2#2T712H /8 1-/0 ?$-$.1e r 41/MG#71$.] Q"?2## 0/%871G.20 J2.2 -/%- /8 7)).$f/M712#] -7#` $` 1-2 )$)G#71/$8 /8?#GH/8% Q-; (I@s*6 2``2?1$."M2M$.] (I@s*6 `$##/?G#7. -2#)2. (I&s*6 Q-& (E&s*6 78H b7MM7"H2#17 Q"?2##0 (@Ps*e r C-/#2 ?]1$1$f/? ,9Ot Q"?2## 0/%871G.2 J70 -/%- /8 $8#] &Ps $` )71/28106 1-2 0/%871G.2 `$. 1-2 ,9IKH/M ?]1$#]1/? 0GD021 $` ZB ?2##0 J70 -/%- /8 EOs $` )71/2810e r Q-2 M$01 /8`.2kG281#] H212?12H %282 0/%871G.20 J2.2 `$. /88712 .20)$802 ?2##"1])20i S701 ?2##0 (Os*6 S7?.$)-7%20 (&&s*6 /MM71G.2 H28H./1/? ?2##0 (&&s* 78H 82G1.$)-/#0 (&;s*e r &K 0/%871G.20 J2.2 0/%8/`/?781#] H/``2.281/7##] 7?1/T712H /8 QZA, ?$M)7.2H 1$ -$.M$82".2?2)1$. )$0/1/T2 (RUt* )71/2810 ()p'e'I .20)2?1/T2#]*i ! KgP 0/%871G.20 M$.2 7?1/T2 /8 QZA, 7.2 700$?/712H J/1- 7H7)1/T2 /MMG82 .20)$802 (2e%e Q"?2## 78H A"?2## 0/%871G.20*m ! EgN 0/%871G.20 700$?/712H J/1- RUt 7.2 .2#712H 1$ /88712 /MMG82 .20)$802 (2e%e 2$0/8$)-/#0 78H H28H./1/? ?2##0*e r L#2T712H ZB ,9IKH/M6 Q-&6 78H 7?1/T712H H28H./1/? ?2## (79,*6 0/%871G.20 J2.2 700$?/712H J/1- %.7H2 @ 1GM$.0 70 J2## 70 J/1- 2#2T712H #2T2#0 $` B/KN ()p'e'''& .20)2?1/T2#]*e r Q-2 M$01 ).2H/?1/T2 QSL 0/%871G.2 `$. )7?#/17f2#"D702H 1-2.7)] J70 Q `$##/?G#7. -2#)2. ?2##0 (Q>R*e Cohort proportion (%) High activity Normal activity Low activity 279 Geparsepto HER2-negative samples 1467 clinical cases 1467 reference clinical cases >1200 example later-stage test cases [Breast n=213] Other Breast o o o o o o o o o o o Mean geneset expression Inferred activity score ! )$%%& ' )$%%& 78 )$%%& 4$D6,<=<) )$%%& ?.@/ G,>DA%B)E=$& H6>+=<I$ <33AD$ ,$&+BD&$ JDD>=$ <33AD$ ,$&+BD&$ K=-$, #E=B=BF<) )$%%& K=-$, Positive correlation Negative correlation (5: K%&$%&'/ @ K%'1"5 RF W881&5 /36"5/ %& 0;5 !54#"P5406 36;6"0 &'E %2820 _MMG82 ?2## ?712%$./20

G*)HI)IJ 2#&$/3#45.67.%881&5)3599./%' /.%&.5#9 ......TNBC (n=74) Inferred activity HR+ (n=205) Significance [-log 10 (p)] p=0.05 Inferred activity G1-2 (n=117) G3 (n=162) Significance

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Page 1: G*)HI)IJ 2#&$/3#45.67.%881&5)3599./%' /.%&.5#9 ......TNBC (n=74) Inferred activity HR+ (n=205) Significance [-log 10 (p)] p=0.05 Inferred activity G1-2 (n=117) G3 (n=162) Significance

TNBC (n=74)HR+ (n=205)

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Model Endpoint odd ratio/hazard ratio(95 CI) p-value

Cox OS 0.55 (0.39-0.77) 0.0005Cox DFS 0.62 (0.47-0.81) 0.0004

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1467 reference clinical cases

>1200 example later-stage test cases

[Breast n=213]

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