Slide 1: Iadademstat Combination with Azacitidine in First Line AML: Final Results of the ALICE Trial
Iadademstat Combination with Azacitidine is a Safe and Effective Treatment in First Line Acute Myeloid Leukemia. Final Results of the ALICE Trial. Olga Salamero1, Tim Somervaille2, Antonieta Molero1, Evelyn Acuña-Cruz3, Jose Antonio Perez-Simon4, Rosa Coll5, Montserrat Arnan6, Brayan Merchan7, Ana P
Slide 2: Disclosures
Disclosures O. Salamero: Abbvie, Celgene/BMS, Novartis:, Astellas, Jazz Phamaceuticals Consultancy or Honoraria. T. Somervaille: Oryzon Genomics, Bristol Myers Squibb, Abbvie, Novartis: Consultancy; Imago Biosciences, CellCentric Ltd: Research Funding. A. Molero: Oryzon Genomics: Consultancy. JA. Pe
Slide 3: LSD1/KDM1A, an epigenetic enzyme with key roles in oncology
LSD1/KDM1A, an epigenetic enzyme with key roles in oncology LSD1 (Lysine demethylase 1) is an epigenetic enzyme (eraser) with catalytic histone demethylase activity that regulates gene expression by altering chromatin structure, acting both as a transcriptional corepressor (on H3K4me1/2) and as a tr
Slide 4: Iadademstat (ORY-1001) is a potent, selective, oral LSD1 inhibitor
Iadademstat (ORY-1001) is a potent, selective, oral LSD1 inhibitor iadademstat • Iadademstat is an irreversible, highly selective, potent, small molecule LSD1 inhibitor Differentiation genes • Covalently binds to FAD-cofactor of LSD1 and inhibits its catalytic and scaffolding activity by preventing
Slide 5: ALICE: iadademstat+azacitidine in first line, unfit, AML patients
ALICE: iadademstat+azacitidine in first line, unfit, AML patients “A Phase IIa study to assess the safety, tolerability, dose finding and efficacy of ORY-1001 in combination with azacitidine in adult patients with AML in first line therapy” Iadademstat 60 or 90 μg/m2 5dON-2dOFF PO each week KEY ENDP
Slide 6: Demographics
Demographics ECOG: Eastern Cooperative Oncology Group; TET2: Tet Methylcytosine Dioxygenase 2’ coding gene; RAS: Rat Sarcoma virus gene family coding gene; RAF: MAP kinase kinase kinase (MAP3K) coding gene; MAPK: Mitogen-activated protein kinases; NF1: Neurofibromatosis type 1 gene; PTPN11: non-rece
Slide 7: Patients disposition
Patients disposition 36 Patients treated Disposition n=36 pts accrued and treated 2 protocol major deviations Reason for treatment discontinuation n (%) 60 90 Overall 34 enrolled per protocol μg/m2/d μg/m2/d 16 at 60 μg/m2/d cohort 7 died before 1st assessment: n=17 n=19 n=36 18 at 90 μg/m2/d cohort
Slide 8: Safety
Safety n=36 Safety Analysis Population Preferred Term SAEs n (%) AEs G3-4 Related AEs (in >1 pt) (in >2 pt) (>10%) Overview of AEs#4 AEs (n) Investigations 60 90 60 90 Platelet ct decreased 0 32 (88.9) 23 (63.9) Overall Overall Subjects with μg/m2/d μg/m2/d n=36 μg/m2/d μg/m2/d n=36 Neutrophil ct de
Slide 9: Efficacy: Responses
Efficacy: Responses ALIVE Ofte, Oncu UKN UKN UKN Responses as recorded in eCRF by investigators for the efficacy population. First, last and changes in assessments indicated. Summary of Responses YEAR I YEAR2 YEAR3 YARS] n=27 n % PETS T*Ts ToT Ts Ts Tote te ys Tats TTS Tete Tots Tope ts Taps tts tet
Slide 10: Efficacy: Responses by AML subtype, risk and mutation profile
Efficacy: Responses by AML subtype, risk and mutation profile Responses for mutations found in 3 or more evaluable patients 6/7 monocytic AML subtype (M4/M5) are CR/CRi % responders out Mutation of evaluable mutated patients TP53 6/8 (75%) TET2 6/8 (75%) RAS pathway 7/7 (100%) DNM3TA 6/6 (100%) SRF2
Slide 11: Efficacy: OS
Efficacy: OS Efficacy analysis set (n=27) 60 μg/m2/d 90 μg/m2/d Overall n=13 n=14 n=27 Median [95% CI] 8.1 [4.5, NE] 12.3 [2.0, NE] 11.1 [4.5, NE] 69.2% Follow up time (mos) Median [95% CI] 21.9 [15.3, NE] 38.6 [12.4, NE] 21.9 [13.8, 38.6 ] 64.3% 50.0% 41.7% 46.2% 36.0% 6 mos 12 mos 18 mos CI: Confi
Slide 12: Efficacy: Responses, exposure and TE by dose cohort
Efficacy: Responses, exposure and TE by dose cohort • Patients with deeper responses show median Higher Ctrough and LSD1 TE are achieved (n=13) iadademstat Ctrough levels achieved in the in the 90 μg/m2/d dose cohort majority of patients in the 90 μg/m2/d cohort CR/CRi 39% ORR 85% CR/CRi 65%
Slide 13: Conclusions
Conclusions The combination of iadademstat with azacitidine appears to be safe and effective for the treatment of newly diagnosed unfit AML patients. Toxicity is manageable with no significant non-hematological toxicity observed 81% of evaluable patients responded. Responses are rapid, deep and
Slide 14: Acknowledgements
Acknowledgements To the patients and their families who made this trial possible To the clinical study teams for their excellent work, especially given the very difficult times during which the study was conducted The study is supported by Oryzon Genomics S.A. Questions to: Olga Salamero, osal