Oncternal Therapeutics (ONCT) Company Presentation summary

Pipeline and product candidates

• ONCT-534 is a dual-action androgen receptor inhibitor in Phase 1/2 for resistant metastatic prostate cancer, showing activity against AR mutations and splice variants, with Fast Track designation from the FDA.

• ONCT-808 is an autologous CAR T cell therapy targeting ROR1, demonstrating encouraging clinical activity in aggressive B-cell NHL, including in patients who failed CD19 CAR T therapy.

• Zilovertamab, a monoclonal antibody targeting ROR1, has shown 100% progression-free survival in CLL patients with TP53 aberrations and is under further investigation.

• The pipeline includes multiple modalities (small molecule, CAR T, antibody) and targets both hematological malignancies and solid tumors.

• Multiple clinical catalysts are expected within the current cash runway, including data readouts for ONCT-534 and ONCT-808 in 3Q 2024.

Clinical and preclinical data

• ONCT-534 demonstrates anti-tumor activity in both enzalutamide-sensitive and -resistant prostate cancer models, including those with AR-V7 splice variants.

• ONCT-534 induces degradation of both native and splice variant AR via ubiquitination and proteasomal pathways, requiring the AR N-terminal domain.

• ONCT-808 CAR T cells show strong anti-tumor activity in ROR1+ mantle cell lymphoma xenograft models and persistence in treated patients.

• Zilovertamab combined with ibrutinib in CLL patients with TP53 mutations achieved prolonged progression-free survival and was well tolerated.

• ROR1 is highly expressed in aggressive B-cell malignancies and many solid tumors, supporting its selection as a therapeutic target.

Clinical development and milestones

• ONCT-534 Phase 1/2 study has fully enrolled its sixth dose cohort (1200 mg daily) in mCRPC, with initial data expected in 3Q 2024.

• ONCT-808 Phase 1/2 study is open and enrolling, with protocol amendments to enhance safety and eligibility; initial data update expected in 3Q 2024.

• Zilovertamab is being further investigated in CLL and other tumor types, with ongoing discussions for partnerships and collaborations.

• The company is supported by experienced scientific and clinical advisory boards in both prostate cancer and cell therapy.

• Cash and short-term investments of $27.0M as of March 31, 2024, provide runway into Q1 2025.