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Table 10: ALPN-101 Flow Cytometric Raw Binding Values (MFI): Rat Counter Structures
Counter Structure Protein Conc. (pM) ALPN-101 ALPN-101 WT ICOSL-Fc1.1 WT ICOSL-Fc1.1 Fc 1.1 Fc 1.1
CD28 100000 80195 78791 7454 7415 702 816
20000 85084 84062 5402 5371 340 656
4000 95160 91524 4817 5891 349 426
800 24943 25244 5995 4876 500 343
160.0 6125 6122 2961 2690 407 431
32.0 1741 1820 1009 1035 299 363
6.4 880 849 553 604 360 458
1.3 641 504 472 444 286 466
ICOS 100000 98614 74753 88764 91881 346 338
20000 105843 108277 101601 99196 189 273
4000 116478 112805 112726 108867 173 167
800 27240 29128 27322 27776 237 352
160.0 6202 6390 6312 6659 167 158
32.0 2019 2336 2295 2162 291 1862
6.4 824 976 984 897 195 464
1.3 449 690 849 547 151 27980
CTLA-4 100000 39728 47060 1820 1775 321 273
20000 45720 40828 1102 1255 343 476
4000 53506 54048 1450 1180 189 300
800 19778 18124 1605 1201 211 230
160.0 4692 4829 1362 1266 271 438
32.0 1942 1678 709 849 293 200
6.4 1074 759 919 909 221 248
1.3 985 1065 695 862 284 609
Pharmacology Study Report Alpine Immune Sciences, Inc. ALPN100-PHRM-001
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Table 11: ALPN-101 Flow Cytometric Raw Binding Values (MFI): Mouse Counter Structures
Counter Structure Protein Conc. (pM) ALPN-101 ALPN-101 WT ICOSL-Fc1.1 WT ICOSL-Fc1.1 Fc 1.1 Fc 1.1
CD28 100000 83572 91398 5445 6948 322 300
20000 80814 81971 3961 4032 353 486
4000 89055 93162 3485 3282 284 378
800 25829 25944 3818 3684 245 310
160.0 6174 6235 1879 2070 243 371
32.0 1749 2036 1101 1012 251 314
6.4 1181 885 925 560 328 311
1.3 508 434 322 483 240 348
ICOS 100000 115099 119796 93680 115950 424 540
20000 115509 126740 117357 117763 391 408
4000 99066 86803 84748 91767 328 318
800 42233 41400 43939 37197 378 272
160.0 11003 10863 11799 11055 473 389
32.0 3155 3081 3282 3073 364 10380
6.4 1227 1419 1406 1328 391 1038
1.3 1280 585 1176 1342 548 3710
CTLA-4 100000 43619 49854 2259 1993 280 635
20000 47422 47943 764 786 389 354
4000 40164 51252 639 646 346 378
800 16193 15472 493 664 228 267
160.0 4168 4097 520 616 236 297
32.0 1299 1297 340 330 283 337
6.4 556 643 434 326 324 285
1.3 333 444 457 579 324 764
Pharmacology Study Report Alpine Immune Sciences, Inc. ALPN100-PHRM-001
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Table 12: ALPN-101 Flow Cytometric Raw Binding Values (MFI): Mock Transfectants
Counter Structure Protein Conc. (pM) ALPN-101 ALPN-101 WT ICOSL-Fc1.1 WT ICOSL-Fc1.1 Fc 1.1 Fc 1.1
100000 6880 5606 2919 4470 297 321
20000 4901 4094 2074 485 194 160
4000 7225 2987 159 281 199 128
800 5994 8204 287 550 132 115
160.0 2671 2370 205 502 166 109
32.0 809 1091 219 239 618 1699
6.4 622 474 142 127 10791 214
1.3 657 188 164 254 184 294
Pharmacology Study Report Alpine Immune Sciences, Inc. ALPN100-PHRM-001
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Table 13: ALPN-101 BLI Binding Responses for Each Replicate in the Titrations
ICOS CD28 CTLA-4
Conc. (nM) Response Conc. (nM) Response Conc. (nM) Response
144.1 0.769 138.2 0.562 500 0.237
144.1 0.765 138.2 0.626 500 0.269
144.1 0.766 138.2 0.622 500 0.266
72.1 0.551 69.1 0.518 250 0.259
72.1 0.624 69.1 0.514 250 0.276
72.1 0.612 69.1 0.485 250 0.267
36 0.447 34.6 0.426 125 0.228
36 0.479 34.6 0.402 125 0.225
36 0.439 34.6 0.363 125 0.221
18 0.292 17.3 0.299 62.5 0.161
18 0.331 17.3 0.298 62.5 0.168
18 0.323 17.3 0.258 62.5 0.163
9.01 0.166 8.64 0.203 31.3 0.113
9.01 0.215 8.64 0.203 31.3 0.12
9.01 0.208 8.64 0.153 31.3 0.104
4.68 0.087 4.32 0.123 15.6 0.07
4.68 0.123 4.32 0.085 15.6 0.062
4.68 0.141 4.32 0.137 15.6 0.069
2.25 0.08 2.16 0.076 7.81 0.037
2.25 0.074 2.16 0.044 7.81 0.034
2.25 0.075 2.16 0.074 7.81 0.034
Schedule 1.97-C
ALPN-202
ALPN-202 is a homodimeric Fc1.1-fusion protein consisting of 2 identical variant CD80 IgV Fc1.1-fusion protein chains covalently linked through the Fc Hinge region disulfide bonds. Each chain contains a variant CD80 IgV domain fused amino-terminally to the variant human IgG1 Fc designated as Fc1.1.
The amino acid sequence of ALPN-202 is set forth below:
VIHVTKEVKEVATLSCGYNVSVEELEQTRIYWQKDKKMVLTMMSGDLNIWPEYKNRTIFDDITNNLSIMILGLRPSDEGTYECVVLKYEKGAFKREHLAEVTLSVKADGSGGGGSEPKSSDKTHTCPPCPAPEAEGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
Schedule 1.120
Option Exercise Data Package
The Option Exercise Data Package shall include all Clinical Data, including: ALPN-101 Clinical Data, Regulatory Documentation and other Information resulting from the Development Activities or the aGVHD Clinical Study conducted on or prior to (i) in the case of Clinical Information (as defined below), the Option Exerci...