cellcell fusion dependent reaction osteoclast dependent reaction agedependent reaction Common precursor cell Multinuclear osteoclast Bone resorption Osteoclast precursor cell cellcell fusion ID: 1042219
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1. Figure 1macrophageCD26cell-cell fusion dependent reaction osteoclast dependent reactionage-dependent reactionCommon precursor cellMultinuclear osteoclastBone resorptionOsteoclast precursor cell cell-cell fusionBone remodelingMacrophageTRAPBONEHematopoietic stem cell (HSC)CD26CD26 in human osteoclast development
2. ADCCCell deathCelllysisFc receptorFc portionDirect effectsCD26+Figure 2Bone marrow stromal cells (BMSCs)Inhibition of adhesion betweenMM cells and BMSCsVCAM1VLA4Humanized anti-CD26 monoclonal antibody (huCD26mAb): Mechanisms of action
3. Summary of Clinical Trials in Anti-CS1 /SLAMF7 Antibody in relapsed/refractory MM Table 1(a)References Phase Regimen ORR(%) PFS(mo) OSRichardson, et al Lonial, et al et al Dimopoulos, et alJakubowiak, et al Zonder, et al Jakubowiak, et al Lonial, et al 2322111Elo+RdRd +/- EloPd +/- EloBd +/- EloElo Dose EscalationElo+BdElo+Rd84%79% vs 66%53% vs 26%66% vs 63%48%82%NA19.4mo vs 14.9mo10.3mo vs 4.7mo9.7mo vs 6.9 moNA9.5moNAMTD not identifiedMM, multiple myeloma; Elo, elotuzumab; Rd, lenalidomide plus dexamethasone; Pd, pomalidomide plus dexamethasone; Bd, bortezomib plus dexamethasone, NA, not available; MTD, maximum tolerated doseELOAUENT2Elo-BdPhase1 EloElo-BdElo-RdNANANA1yr85% vs 74%NANANA
4. Summary of Clinical Trials in Anti-CD38 Antibody in relapsed/refractory MM Table 1(b) References Phase Regimen ORR (%) PFS (mo) OSLokhorst, et al Lonial, et al Spencer, et al Palumbo, et al Dimopoulos, et al Dimopoulos, et al Chari et al 1/223331bDara monotherapyDara monotherapyBd +/- DaraBd +/- DaraRd +/- DaraRd +/- DaraPd +/- Dara36%17%83% vs 63%83% vs 63%93% vs 76%93% vs76%60% 5.6 mo3.7mo1.5yr 48% vs 8%1yr61% vs 27%1yr 83% vs 60%2yr 68% vs 41%1yr 42%MM, multiple myeloma; Dara; daratumumab, Rd, lenalidomide plus dexamethasone; Bd, bortezomib plus dexamethasone; Pd, pomalidomide plus dexamethasone; NA, not available; MTD, maximam tolerated doseGEN501SIRIUSCASTORCASTORPOLLUXPOLLUXEQULLEUS1yr77%1yr65%NANANANA1yr 89%
5. Investigational monoclonal antibodies in MMTarget molecule mAb Type Clinical trials CD138CD56CD40CD74BAFFBCMAGRP78IGF-1RICAM-1CD26Indatuximab ravtansine LorvotuzumabDacetuzumab, LucatumumabMilatuzumabTabalumabGSK2857916PAT-SM6AVE1642BI-505YS110 (huCD26mAb)ADCADCHumanizedHumanizedHumanizedADCHumanizedHumanizedHumanizedHumanizedADC, antibody drug conjugate; Lena, lenalidomide; Inda, Indatuximab ravatansine, Rd, lenalidomide plus dexamethasone; Lorv,lorvotuzumab; Luc, Lucatumumab; PR, partial response; Bd, bortezomib+dexamethasone; Taba, tabalumab; MTD, maximum tolerated doses;Inda +/-RenaLorv +/ RdLuc; 4% attained prolonged PRNo objective responsesBd+Taba; ORR 44%MTD not determinedMTD not determinedNo objective responsesNo objective responsesBest responses 50%ORR 78% vs 4%ORR 56% vs 7%Table 2