Oryzon Genomics (ORY) investor relations material

Business and AML treatment opportunity

• Madrid-listed; market capitalization cited at ~$250 million, cash of $25 million as of Sept. 1, and ~50 staff across Barcelona and Boston.

• AML causes 22,000–23,000 new U.S. cases annually; cited 5-year survival for patients over 70 is 4%.

• HMA-VEN improves outcomes for older or intensive-chemotherapy-ineligible patients but is not curative for most; unmet need remains in suboptimal responders without actionable biomarkers, including TP53/RAS-mutated and monocytic AML.

• Venetoclax plus azacitidine was described as standard therapy for most patients unable to undergo stem-cell transplantation; HMA-VEN is also increasingly used as a bridge to transplant.

Iadademstat and ALICE-2 clinical evidence and safety

• Iadademstat inhibits LSD1, aiming to restore leukemia-cell differentiation and programmed cell death; the rationale also cites immune activity and effects on leukemic stem cells.

• ALICE-2 evaluates iadademstat added to venetoclax/azacitidine; interim results showed 95% ORR, 84% composite CR and 74% pure CR, with responses by cycle 1 or 2 and median follow-up of 8 months.

• Median OS and EFS were not reached; low-dose response was 75% (one non-response among four patients) and high-dose response was 100% among 15 patients, with similar tolerability across doses.

• ALICE-2 subgroup results included responses in 2/2 TP53-mutated and 4/4 RAS-pathway-mutated patients, all with pure CR; median OS was not reached in either subgroup.

• Safety included 0% 30-day mortality and 6% 60-day mortality (one unrelated event); common grade ≥3 AEs were thrombocytopenia and neutropenia, with 3 DL2 DLTs and 2 grade 5 sepsis events deemed unrelated to study drugs.

Competitive positioning and patient subgroups

• Iadademstat was presented as mutation-agnostic; cited CR rates for menin-inhibitor comparators were 81%, 73% and 68%, versus 78% for iadademstat.

• Against all-comer antibody approaches, cited composite CR was 85% versus 79% for pivekimab, and pure CR was 74% versus 63%; comparisons were preliminary.

• Cited median OS was 14 months across AML, nearly 27 months without aggressive mutations, 12 months for intermediate-risk mutations and 5 months for TP53-mutated disease.

• Prior-trial results included TP53 response of 75%, CR of 63% and doubled median OS; intermediate-risk patients had 100% response and a 25% increase in median OS. M4/M5 patients had 86% composite CR, with median OS not reached.