Exhibit 99.2
Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Juan F. Vera and Ann M. Leen
Infusion Tumor - specific T cells Antigen Specificity Patient Adoptive T cell transfer Blood draw PBMCs
• Simultaneously target multiple TAAs • Target multiple epitopes (CD4 and CD8) within each antigen • T cells with native T cell receptor specificity (non - engineered) Our approach
MultiTAA T cells MultiTAA T cell therapy for lymphoma MAGEA4 PRAME Survivin NYESO1 SSX2
Activation DC Overlapping pepmixes PBMCs MultiTAA T cells Expansion MultiTAA - T Cell manufacture
0 20 40 60 80 100 % Positive cells MultiTAA - T Cell Phenotype n=39 CD4 CD8 CD3 DC TCM TEM NK
SFC/2x10 5 cells MultiTAA - T Cell Specificity SSX2 MAGEA4 PRAME Survivin NYESO1
% Specific Lysis Multi TAA - T Cell Autoreactivity E:T of 20:1
Any patient > 18 yrs with HL or NHL Active disease - in 2 nd or subsequent relapse - in 1 st relapse for indolent lymphoma after 1 st line therapy for relapse - in 1 st relapse if immunosuppressive chemotherapy contraindicated - primary refractory disease or persistent disease after 1 st line therapy - multiply relapsed patients in remission at a high risk of relapse - lymphoma as a second malignancy e.g. Richters After autologous or syngeneic SCT (adjuvant therapy) Clinical Trial: Eligibility Infusion of multiTAA - T cells specific for PRAME, SSX2, MAGEA4, NYESO1, Survivin
Antigen Escalation Phase = fixed dose 5x10 6 /m 2 – 2 pts/stage : Day 0: PRAME - specific T cells Day 28: PRAME and SSX - specific T cells Stage Two : Day 0: PRAME and SSX - specific T cells Day 28: PRAME/SSX/MAGE - specific T cells Stage Three : Day 0: PRAME/SSX/MAGE - specific T cells Day 28: PRAME/SSX/MAGE/NYESO1 - specific T cells Stage Four: Day 0: PRAME/SSX/MAGE/NYESO1 - specific T cells Day 28: PRAME/SSX/MAGE/NYESO1/Survivin - specific T cells Safety of MultiTAA T cells - Antigen escalation
PRAME/SSX/MAGE/NYESO1/Survivin - specific T cells : 2 - 4 pts at each level, 2 infusions 14 days apart Dose Level 1 : Day 0 and 14: 5x10 6 cells/m 2 Dose Level 2 : Day 0 and 14: 1x10 7 cells/m 2 Dose Level 3 : Day 0 and 14: 2x10 7 cells/m 2 Safety of MultiTAA T cells - Dose escalation
Clinical Trial: Treatment • 33 patients infused
Antigen escalation (n=4) Antigen escalation (n=4) Dose escalation (n=14) Dose escalation (n=11) Clinical Trial: Treatment Group B: Active lymphoma (failed prior lines) Group A: In remission • 33 patients infused
- 33 patients infused (0.5 - 2x10 7 cells/m 2 ) - 12 HL - 19 aggressive NHL (DLBCL/mantle/peripheral T) - 2 with composite lymphoma - No lymphodepletion - No adverse events Clinical Trial: Treatment
0 20 40 60 80 100 120 140 Pre Post Non - targeted antigens NYESO1 AFP Non - targeted antigens Pt1 (HL) – Clinical and Immune effects Post CTLs + radiation 0 10 20 30 40 50 60 70 80 90 Prame SSX2 MAGE A4 NYESO - 1 Survivin No pep Pre #1 wk1 wk2 Pre #2 mth3 S F C / 5 x 1 0 e 5 A B Pre T cells Post CTLs + radiation 0 10 20 30 40 50 60 70 80 90 Prame SSX2 MAGE A4 NYESO - 1 Survivin No pep Pre #1 wk1 wk2 Pre #2 mth3 S F C / 5 x 1 0 e 5 A B Post T cells SFC/2x10 5 0 10 20 30 40 50 Pre Post Targeted Antigens SSX2 PRAME Targeted antigens
0 20 40 60 80 100 120 140 160 180 200 PRE MTH3 MTH9 Survivin NYESO1 MAGEA4 SSX2 PRAME SFC/2x10 5 Pre Mth3 Mth9 Targeted antigens Non - targeted antigen Mth 3 Mth 9 Pre - Infusion 0 5 10 15 20 25 30 35 40 45 Pre Mth3 Mth9 MAGEC1 SFC/2x10 5 Pt2 (NHL) - Clinical and Immune effects
- 18 patients infused as adjuvant - 15/18 in remission (median 19 months) Clinical Outcomes – Adjuvant Clinical Outcomes – Adjuvant
Clinical Outcomes – Adjuvant ID Age/Sex Disease Prior Therapies Response to T cell therapy (duration) 1 * 39/M HL & DLBCL ABVD RICE ASCT CCR (>3 years) 2 * 78/F DLBCL R RCHOP In remission (8 mo ) relapse 3 * 78/F DLBCL R RCHOP multiTAA T cells R - Bendamustine CCR (>3 years) 4 * 21/M HL ABVD Brentuximab Nav /Gem ASCT CCR (>4 years) 5 34/M HL ABVD ICE ASCT + XRT Brentuximab In remission (12 mo ) relapse 6 54/M DLBCL RCHOP R - EPOCH R - DHAP ASCT In remission (19 mo ) relapse 7 61/M DLBCL R - EPOCH ASCT XRT CCR (>2 years) 8 41/F HL ABVD + XRT ICE ASCT XRT Brentuximab DHAP CCR (>4 years) 9 62/M T cell CHOP + XRT ASCT CCR (>3 years) 10 53/M Mantle R - HyperCVAD R - Bendamustine R - Ibrutinib ASCT + XRT CCR (>2 years) 11 39 not 67/M Mantle R - Bendamustine - Ara - C ASCT CCR (>3 years) 12 65/F DLBCL R - EPOCH ASCT CCR (>2 years) 13 35/M HL ABVD Brentuximab +Bendamustine ASCT XRT CCR (> 2 years) 14 73/F DLBCL R - CHOP XRT ESHAP RIE CCR (>1 year) 15 50/F DLBCL HyperCVAD ASCT CCR (9 mo ) 16 41/M DLBCL ABVD R - ICE ASCT CCR (> 1 year) 17 32/F T cell ALCL CHOP Brentuximab Crizotinib CD30 CAR T cells Crizoinib CCR (9 mo ) 18 25/M HL ABVD Brentuximab ICE ASCT CCR ( >1 year)
- 15 patients treated for active disease - 6 CRs; 4 SD; 5 PD Clinical Outcomes – Active disease
Clinical Outcomes – Active disease ID Age/Sex Disease Prior Therapies Response to multiTAA T cells (duration) 1 * 31/F HL ABVD ICE Cis - Gem XRT ASCT EBV T cells Brentuximab Yttrium90 CART - CD30 Stable disease (5 mo) Off study [ Revilimid (5 mo ) PD1] 2 * 55/F HL/NHL RCHOP + XRT ICE ASCT CR (4 mo) Died of pneumonia 3 * 38/M HL ABVD XRT IGEV ESHAP ASCT GVD XRT CR (>2 years ongoing) 4 * 44/F HL ABVD ICE ASCT Brentuximab CR (>5 years ongoing) 5 46/M HL ABVD ICE ASCT + XRT Brentuximab CR (>2 years ongoing) 6 46/F DLBCL RCHOP GDC ASCT CR (>3 years ongoing) 7 31/F HL ABVD XRT ICE Nav /Gem ASCT HDACi Brentuximab Bendamustine PD1i Stable disease (5 mo) PD 8 69/M NHL EPOCH Romidepsin ASCT Stable disease (> 2 years) 9 54/M DLBCL RCHOP R - ICE ASCT Stable disease (6 mo ) PD Started PD1i - >2 years; Alive 10 18/F HL ABVE - PC XRT IVBor Brentuximab PD1i Stable disease (9 mo ) PD 11 48/M DLBCL EPOCH - R R - ICE ASCT XRT CR (>1 year) 12 49/M HL ABVD ICE ASCT XRT Brentuximab Nivolumab Bendamustine PD (3 mo ) 13 54/M DLBCL EPOCH - R ICE - R XRT ASCT SD (9 mo ) 14 64/M DLBCL R - CHOP Bendamustine / Rituxan RICE RIE ASCT PD (9 mo ) 15 68/M DLBCL RCHOP GDP ASCT Stable disease (4 mo ) CD19 - CAR - T
• Safe to date • Feasible adjuvant and treatment • In vivo expansion of T cells directed to targeted antigens • Antigen/Epitope spreading • Clinical benefit Summary to date
Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Juan F. Vera and Ann M. Leen