Slide 1: Pooled fecal allogenic microbiotherapy for refractory GI acute GvHD: Early Access Program results
Pooled fecal allogenic microbiotherapy for refractory gastrointestinal acute graft-versus-host disease: results from the early access program in Europe Florent Malard, MD, PhD Sorbonne University, INSERM Clinical Hematology and Cellular Therapy Dpt. Saint-Antoine Hospital Paris, France
Slide 2: Disclosures
EBMT24 2 Disclosures I have the following relationships to disclose: 1. Employment/leadership position/advisory role: No 2. Stock ownership or options: No 3. Patent royalties/licensing fees: No 4. Honoraria: BMS, Therakos/Mallinckrodt, Sanofi, JAZZ Pharmaceuticals, Gilead, Novartis, Astrazeneca and
Slide 3: Fecal microbiotherapy (FMT) and gastro-intestinal acute GvHD
EBMT24 3 Fecal microbiotherapy (FMT) and gastro-intestinal acute GvHD • Treatment of GI-aGvHD is an unmeet medical need • Link between gut microbiota dysbiosis and GvHD outcomes is well established. • FMT was proven to be safe and effective in highly immunosuppressed patients. Promising results wi
Slide 4: aGvHD after ruxo resistance/intolerance: unmet medical need, poor survival
EBMT24 4 aGvHD after ruxo resistance/intolerance: unmet medical need, poor survival No validated treatments are available for acute GvHD that is refractory to steroids and ruxolitinib, and therefore it remains an unmet medical need OS at 6M: 20% OS at 12M: 15% 0,20 0,15 Median survival of 28 (range:
Slide 5: MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD
EBMT24 5 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: GvHD response (all patients) ODD status from EMA and FDA Characteristics Pooled microbiota: a high-richness, high-diversity, full ecosystem, containing ButycoreTM, 24 months stability at -80°C Administrat
Slide 6: MaaT013 Early Access Program (EAP)
EBMT24 6 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Early Access Program (EAP) • In France: Authorized by the French regulator (ANSM) with Governing protocol for use • In other countries in Europe: compassionate use Data from 140 patients treated from July
Slide 7: EAP patient characteristics
EBMT24 7 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Early Access Program (EAP) Characteristics All patients (N=140) • Age, median (range) 58 (12-74) • Gender o Male 77 (55%) o Female 63 (45%) • Disease o Acute myeloid leukemia 55 (39%) o Myelodysplastic sy
Slide 8: aGvHD characteristics
EBMT24 8 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: aGvHD characteristics Characteristics All patients (N=140) • Steroid status o Steroid resistance 115 (82%) o Steroid dependence 25 (18%) • Type of aGvHD o Classical 86 (61%) o Late onset 13 (9%) o Overlap
Slide 9: aGvHD prior therapies
EBMT24 9 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: aGvHD prior therapies Characteristics All patients (N=140) • Median number of previous treatments for aGvHD 2 (1-6) (including CS) (range) o CS 140 (100%) o Ruxolitinib 121 (84%) • Median number of MaaT01
Slide 10: aGvHD response (all EAP patients)
EBMT24 10 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: aGvHD response (all EAP patients) D28 response, N GI Stage 1 GI Stage 2 GI Stage 3 GI Stage 4 Total (%) N= 18 N= 28 N= 38 N= 56 N=140 100 PR • GI-ORR 12 (67%) 20 (71%) 24 (63%) 18 (32%) 73 (52%) VGPR 10
Slide 11: Response in steroid-dependent versus steroid-refractory patients
EBMT24 11 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: aGvHD response in steroid- dependent versus steroid-refractory patients GI response SR-aGvHD, N= 115 SD-aGvHD, N= 25 N (%) GI-ORR 54 (47%) 20 (80%) CR 25 (22%) 14 (56%) VGPR 20 (17%) 6 (24%) PR 9 (8%) 0
Slide 12: Response in ruxolitinib-refractory patients treated as 3rd line (n=49)
EBMT24 12 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: aGvHD response in the ruxolitinib- refractory patients treated with MaaT013 as 3rd line (n=49) 100 PR Response Ruxolitinib refractory in 2nd line, MaaT013 80 VGPR N (%) in 3rd line N=49 CR 63% 61% GI-ORR
Slide 13: Overall Survival (All EAP patients, n=140)
EBMT24 13 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Overall Survival (All EAP patients, n=140) 100 Responders 100 Non responders Overall survival (%) Overall survival (%) 74% 68% 54% 58% 47% 50 42% 50 Log-rank test <0.0001 33% 24% 24% 0 0 0 90 180 270 360
Slide 14: Overall Survival in steroid- and ruxolitinib-refractory patients treated as 3rd line
EBMT24 14 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Overall Survival in steroid- and ruxolitinib- refractory patients treated as 3rd line (n=49) 100 100 Responders Overall survival (%) Overall survival (%) 76% 76% Non responders 64% 52% 49% 50 42% 50 Log-
Slide 15: Safety profile
EBMT24 15 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Safety profile • Overall safety is very good compared to historical data in such heavily pre-treated and fragile population • 2 paediatric patients (aged 12 and 15) treated with MaaT013: well tolerated (
Slide 16: Potential mechanism of action with restoration of homeostasis and gut barrier
EBMT24 16 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: potential mechanism of action with restoration of homeostasis and gut barrier MaaT013 Restoration of microbial resets microbial network homeostasis and network diversity Remission Eradication of MDRB, of
Slide 17: Conclusions
EBMT24 17 MaaT013, an immunosuppressant sparing agent to restore the microbiome and treat aGvHD: Conclusions • MaaT013 is highly effective therapy for SR- and SD-GI- aGvHD • D28 GI-ORR 52% and ORR 52% • Excellent responses in the ruxolitinib-refractory patients (MaaT013 as 3rd line), with high rates
Slide 18: The ARES Phase 3 study: MaaT013 as 3rd line agent in GI aGvHD treatment
EBMT24 18 The ARES Phase 3 study: MaaT013 as 3rd line agent in GI aGvHD treatment Day 28 Primary Month 3 Month 6 Month 12 MaaT013 MaaT013 MaaT013 endpoint 2nd Follow- 3rd Follow-up Final Follow- (enema) (enema) (enema) ORR up up Day 0 Inclusion 5 days 5 days 75 (grade II-IV) allo-HSCT patients Treat
Slide 19: Acknowledgments
EBMT24 19 Acknowledgments Pa t ie nt s , C a re g ive rs a nd He a lt hy Donors involve d • Michael Loschi, Thomas Cluzeau (CHU Nice) • Claude-Eric Bulabois, Martin Carré (CHU Grenoble) • Faezeh Legrand, Reynier Devillier, Angela Granata, • Hélène Lanic, Vincent Camus (Centre Henri Becquerel, Rouen)
Slide 20: Thank you!
AP-HP. Sorbonne Université Inserm @ MEDECINE 2 SORBONNE dela same ete UNIVERSITE de Ia santé at de La rocherche médicale Thank you! ES (Oy EBMT | acy