Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — EHA Hybrid Congress 2024
16 slides from Nurix Therapeutics's conference presentation, Jun 16, 2024
Slide 1: Latest Results from an Ongoing First-in-Human Phase 1a/b Study of NX-5948
Latest Results from an Ongoing First-in-Human Phase 1a/b Study of NX-5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients with Relapsed/Refractory CLL and Other B-cell Malignancies Kim Linton, Graham P. Collins, Francesco Forconi, Nirav N. Shah, Karan Dixit, Talha Munir, Zulfa Omer
Slide 2: Disclosures
Disclosures Disclosures of: Kim Linton Research Speakers Advisory Company name support Employee Consultant Stockholder bureau board Other AbbVie X X X X BeiGene X X BMS X X Celgene X X X Genmab X X X X Kite/Gilead X X Hartley Taylor X Roche X X X X Takeda X 2
Slide 3: Unmet Clinical Need: Relapsed/Refractory CLL
Unmet Clinical Need: Relapsed/Refractory CLL Acquired resistance to BTK inhibitors presents a growing challenge in the treatment of CLL • Targeted therapy focusing on two key pathways (BTK/BCL2) is standard of care in CLL and has changed the treatment landscape in front-line and relapsed/refractory
Slide 4: NX-5948 Mechanism of Action
NX-5948 Mechanism of Action Utilize the ubiquitin-proteasome pathway to degrade BTK, a well-validated target in B-cell malignancies BTK degraders can overcome treatment-emergent resistance mutations BTK degraders address BTK scaffolding function BTK degraders show emerging activity in various B-cell
Slide 5: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a dose escalation Potential Phase 1b dose expansion (N = up to 160 patients) CLL/SLL dose A CLL/SLL dose B CLL/SLL 600 mg QD Prior BTKi and BCL2i Prior BTKi and BCL2i (up to 66 patients) 450 mg Q
Slide 6: Patient Disposition
Patient Disposition Patients were dosed in CLL (n=31) and NHL/WM (n=48) dose-escalation cohorts Screened (N=121)a Screen failure (n=39) DLBCL: n=14 (17.7%)b Assigned cohort MCL: n=12 (15.2%)b (N=79) PCNSL: n=9 (11.4%)b MZL: n=6 (7.6%)b CLL dose escalation NHL/WM dose WM: n=4 (5.1%)b (n=31) escalatio
Slide 7: Baseline Demographics/Disease Characteristics
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Patients with CLL Patients with NHL/WM Overall population Characteristics (n=31) (n=48) (N=79) Median age, years (range) 69.0 (35–88) 66.5 (42–87) 67.0 (35–88) Male, n (%) 19 (61.3) 33 (6
Slide 8: NX-5948 Is Well Tolerated
NX-5948 Is Well Tolerated TEAEs in ≥10% of overall population or grade ≥3 TEAEs or SAEs in >1 patient Patients with CLL (n=31) Overall population (N=79) TEAEs, n (%) Any grade Grade ≥3 SAEs Any grade Grade ≥3 SAEs Purpura/contusiona 13 (41.9) – – 28 (35.4) – – Thrombocytopeniab 7 (22.6) 1 (3.2) – 21
Slide 9: NX-5948 Efficacy: Clinical Response
NX-5948 Efficacy: Clinical Response Broad antitumor activity in CLL as demonstrated by significant lymph node reduction and ORR CLL disease-evaluable patientsa n=26 Objective response rate (ORR)b, % (95% CI) 69.2 (48.2–85.7) Best response, n (%) CR 0 (0.0) PR / PR-L 18 (69.2) % change from baseline
Slide 10: NX-5948 Efficacy: Duration of Treatment
NX-5948 Efficacy: Duration of Treatment Durable responses seen in heavily pretreated patients with CLL Select prior therapies ≥2 prior BCL2i cBTKi ncBTKi BTKi Median duration of treatment, months (range) 2.8 (0.2–15.2) Patients dose escalated during treatment, n 9 * Yes *Patient with Richter’s trans
Slide 11: Case Study: Patient with CLL and CNS Involvement
Case Study: Patient with CLL and CNS Involvement Deepening response over time approaching complete response criteria 8 weeks: Stable Disease Prior treatments LN: –53% (>50% PR) 1. Idelalisib: 2015 – 2018 60 Spleen: –13% (–49% to +49% SD) 2. Venetoclax-Rituximab: 2018 – 2022 ALC Plts: >100 (CR) 3. Ac
Slide 12: Mutation Status and BTK Degradation
Mutation Status and BTK Degradation NX-5948 induces rapid and robust degradation of wild-type and mutant BTK Patients with CLL BTK degradation in CLL with BTK mutations (n=30) 5000 Wildtype Wild type(n=15) (n=15) Mutation status, n (%) (background subtracted) 4000 BTK T474F/I BTK T474F/I (n=3) (n=3)
Slide 13: Clinical Activity in Patients with Baseline Mutations
Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-treat CLL patient population • No genotypic profile was linked to * i
Slide 14: Clinical Activity in Patients with Baseline Mutations
Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-treat CLL patient population • No genotypic profile was linked to * i
Slide 15: Conclusions
Conclusions: Positive results from the ongoing Phase 1 study of novel BTK degrader NX-5948 • NX-5948 was well tolerated in patients with NHL and CLL, with no increased safety signal at higher doses • Deep and durable clinical responses were observed in a difficult-to-treat CLL patient population: –
Slide 16: Acknowledgements
Acknowledgements Participating Global Sites • The authors are grateful to the patients and their families who USA UK enrolled in this trial Cayuga Cancer Center, Ithaca, NY Barts Cancer Institute, Queen Mary University City of Hope National Medical Center, Duarte, CA of London • The authors would al