Cypherpunk Technologies Inc. · NASDAQ:CYPH
Cypherpunk Technologies — Leap Therapeutics — Investor Presentation (April 2024)
45 slides from Cypherpunk Technologies's investor presentation, Apr 11, 2024
Slide 1: Company presentation, Leap Therapeutics, April 2024
company presentation LEAP THERAPEUTICS April 2024
Slide 2: Forward looking statements
Forward looking statements 2 This presentation contains forward - looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, clinical t
Slide 3: Developing biomarker-targeted antibody therapies for cancer patients
Developing biomarker - targeted antibody therapies for cancer patients 3 Tw o clinical stage antibody programs – DK N - 0 1 targeting DKK1 FL - 301 targeting CLDN18.2 Upcoming multiple milestones from two randomized clinical trials Biomarker strategy, focus on GI cancers Cash runaway to 202 6 with $
Slide 4: Pipeline
Pipeline 4 Treatment: Indication: Preclinical Phase 2 Phase 3 Partners: Phase 1 DKN - 01 Anti - DKK1 antibody tislelizumab + chemotherapy bevacizumab + chemotherapy pembrolizumab FL - 302 (NBL - 016) Anti - CLDN18.2/CD137 bispecific antibody FL - 301 (NBL - 015) Anti - CLDN18.2 antibody Gastric canc
Slide 5: Anti-DKK1 monoclonal antibody
DKN - 01 Anti - DKK1 monoclonal antibody
Slide 6: The role of DKK1 in cancer
The role of DKK1 in cancer 6 Tumor CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells DKK1 is produced and secreted by cancer cells, and functions on several tumor pathways and nearby immune cells. Enhances the suppressive activity of MDSCs and M2 macrophages. Reduces NK cell activity and T - cell
Slide 7: Activity of DKN-01 to treat cancer
Activity of DKN - 01 to treat cancer 7 CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells Tumor Cancer cell DKK1 DKN - 01 treatment neutralizes DKK1 and stimulates an immune mediated anti - tumor response. DKN - 01 DKN - 01 activates NK cells, reprograms macrophages into the tumor - attacking M1 s
Slide 8: DKN-01 and anti-PD-1 cooperativity
DKN - 01 and anti - PD - 1 cooperativity 8 Anti - PD1 Anti - PD1 PD1 DKN - 01 targets innate immunity by activating NK cells, reprogramming Macrophages and inhibiting MDSCs, thus setting the stage for an enhanced adaptive immune response by anti - PD - 1. Promotes a pro - inflammatory M1 macrophage
Slide 9: Gastric cancer development
DKN - 01 Gastric с ancer development
Slide 10: DKK1-high levels are associated with poor survival in gastric cancer
DKK1 - high levels are associated with poor survival in gastric cancer 10 Strata 21 34 7 1 1 20 4 0 300 200 100 0 time to treatment discontinuation (days) High l evels of DKK1 c orrelate with s horter o verall s urvival In g astric c ancer TCGA STAD d ataset DKK1 - high i s a ssociated with p oor r
Slide 11: Single agent activity in heavily pretreated esophagogastric cancer patients
DKN - 01 single agent activity in heavily pretreated esophagogastric cancer patients 11 Baseline 4 - month scan On Study 1 Year, Reduction - 33.9% Failed Prior anti - PD - L1 + IDOi Best Overall Response of 20 Evaluable Patients* Partial Response 2 Stable Disease 6 Progressive Disease 12 *By Blinded
Slide 12: Clinical activity of DKN-01 plus paclitaxel or anti-PD-1 antibody
*DKK1 - high ≥ upper tertile (35) Clinical activity of DKN - 01 plus paclitaxel or anti - PD - 1 antibody 12 PD PD PD PD PD PD PD PD PD PD PD SD SD SD SD SD SD SD SD SD SD SD SD SD SD SD SD SD SD SD PD PD PD PD PD PD PD PD PD PD PR PR PR PR PR PR PR PR PR PR PR PR PR PD PD PD PD PD PD PD PD PD PD PD
Slide 13: Response by DKK1 expression in first-line patients
mITT * population N=22 DKK1 - high N=10 DKK1 - low N=9 DKK1 - unknown N=3 CR - complete response 1 (5%) 0 1 (11%) 0 PR - p artial response 1 5 (6 8 %) 9 (90%) 5 ( 56 %) 1 (33%) S D - s table disease 5 (23%) 0 3 ( 33 %) 2 (67%) PD - p rogressive disease 0 0 0 0 NE - non - evaluable 1 (5%) 1 (10%) 0 0
Slide 14: Response by PD-L1 expression
Response by PD - L1 expression 14 86 % ORR in PD - L1 low patients Best % change in sum of diameters vCPS : visually - estimated combined positive score; PD - L1 : programmed death - ligand 1 *Includes one pathologic CR As presented at ASCO 2023 1L GEJ/GC DKN - 01 + t islelizumab + chemotherapy CR -
Slide 15: Progression-free survival
Progression - free survival 15 Overall Population DKK1 - high: H - score ≥35; | DKK1 - low: H - score <35 | PD - L1: Programmed Death - Ligand 1 | vCPS: Visually - Estimated Combined Positive Score As presented at ASCO 2023 ≥5 <5 Unknown 6 5 4 3 2 2 16 8 7 15 13 12 10 7 6 4 10 3 0 3 3 2 1 1 1 0 2 2
Slide 16: Overall survival
Overall survival 16 DKK1 - high: H - score ≥35; | DKK1 - low: H - score <35 | PD - L1: Programmed Death - Ligand 1 | vCPS: Visually - Estimated Combined Positive Score As presented at ASCO 2023 Overall Population ≥5 <5 Unknown 6 5 3 4 4 4 6 5 5 Obverall 25 2 1 20 19 0 7 6 3 24 9 2 3 4 5 9 12 21 10 6
Slide 17: DKK1 and PD-L1 expression are not correlated
DKK1 and PD - L1 expression are not correlated 17 This population had low overall PD - L1 expression 1L GEJ /GC DKN - 01 + t islelizumab + chemotherapy 200 300 100 40 10 50 80 20 60 90 30 70 100 0 DKK1 expression (H - score) 0 - 300 PD - L1 expression (CPS) 0 - 100 DKK1 0 Spearman correlation r = 0.
Slide 18: Competitive benchmarks for anti-PD-1 plus chemotherapy in 1L GEJ/GC patients
Competitive benchmarks for anti - PD - 1 + chemotherapy in 1L GEJ/GC patients 18 Nivolumab Checkmate - 649 OR R (%) (95 % CI) 50.4% (44.3%, 56.4%) 50% (46% , 55%) 47% (43% , 50%) 9.0 (8.2, 19.4) 9. 6 (8. 2 , 1 2.4 ) 8.5 (7. 7 , 9.9) 8.3 (7.0 , 9.3 ) 7.7 (7.1 , 8.6 ) ) 8.6 (7.9, 11.1) DO R mo n ths (
Slide 19: Rationale-305 study: tislelizumab plus chemotherapy in 1L GEJ/GC
19 OR R (%) (95 % CI) DO R mo n ths (95% CI) P F S mo n ths (95% CI) O S mo n ths (95% CI) HR (95% CI) HR (95% CI) HR (95% CI) All Patients 40.5 % ( 36.2 % , 45.0 %) 47 .3 % (4 2.9 % , 5 1.8 %) 6.2 (5.6, 6.9 ) 6.9 (5.7, 7.2 ) 12.9 ( 12.1, 14.1 ) 15.0 (1 3.6 , 16.5 ) 8.6 ( 7.9, 11.0 ) 7.2 ( 6.0, 8.5
Slide 20: DisTinGuish Part C randomized study
DisTinGuish Part C randomized study 1L GEJ/GC DKN - 01 + t islelizumab + chemotherapy 20 DKN - 01 + tislelizumab + SOC chemotherapy (XELOX or mFOLFOX6) Tislelizumab + SOC chemotherapy (XELOX or mFOLFOX6) N=8 5 N=8 5 Stratification factors: • DKK1 expression (TPS ≥ 20% vs < 20%) • PD - L1 (CPS ≥5 vs
Slide 21: Colorectal cancer development
DKN - 01 Colorectal cancer development
Slide 22: Rationale for targeting colorectal cancer with DKK1 expression
Rationale for targeting colorectal cancer with DKN - 01 DKK1 expression is the highest in metastatic rectum 22 • CRC is characterized by hyperactivation of the Wnt pathway, often believed to be the initiating and driving event • Consensus Molecular Subtype 2 primarily in left - sided tumors • DKK1 h
Slide 23: DKN-01 has activity in CRC models with bevacizumab or 5FU
DKN - 01 has activity in CRC models in combination with bevacizumab or 5FU HCT116 • DKN - 01 has efficacy in CRC syngeneic models including HCT116 • Additive activity was seen with bevacizumab • In a 5FU chemotherapy - resistant model, DKN - 01 demonstrates significant inhibition of tumor growth alo
Slide 24: DeFianCe study design: advanced colorectal cancer
DeFianCe study design: advanced colorectal cancer 24 Randomized phase 2 study of FOLFIRI/FOLFOX and b evacizumab +/ - DKN - 01 as second - line treatment of advanced colorectal cancer 2L CRC DKN - 01 + bevacizumab + chemotherapy Primary objective: PFS , left - side and all Secondary objectives: – OR
Slide 25: Overall response rate exceeded 20% target with high disease control rate
Overall response rate exceeded 20% target with high disease control rate 25 ORR in RE patients : 8/27 = 30% DCR in RE patients : 25/27 = 93% Objective Response Rate (%) Disease Control Rate (%) Partial Response n (%) Stable Disease n (%) Progressive Disease n (%) Overall, n=27 30 93 8 (30) 17 (63) 2
Slide 26: Greater activity in left-sided tumors subgroup
Greater activity in left - sided tumors subgroup 26 • 9 patients who remain on study therapy are left - sided, 6 of whom are rectal/rectosigmoid patients Treatment ongoing Overall, n=27 Objective Response Rate (%) Disease Control Rate (%) Partial Response n (%) Stable Disease n (%) Progressive Disea
Slide 27: Enriched responses in rectal/rectosigmoid cancer patients
Enriched responses in rectal/rectosigmoid cancer patients 27 Overall, n=13 Objective Response Rate (%) Disease Control Rate (%) Partial Response n (%) Stable Disease n (%) Progressive Disease n (%) Rectal 46 100 6 (46) 7 (54) 0 (0) 6 of the 8 responding patients were in the rectal / rectosigmoid sub
Slide 28: Duration of clinical benefit
28 Duration of clinical benefit Tumor sidedness subgroup As presented at ASCO GI 2024 2L CRC DKN - 01 + bevacizumab + chemotherapy
Slide 29: Progression-free survival
Progression - free survival 29 Median PFS : 6.3 months 6 - month PFS rate : 55.2% • Heterogeneous population included many unfavorable subgroups • 9 patients remain on therapy at a minimum of 8.5 months on therapy As presented at ASCO GI 2024 2L CRC DKN - 01 + bevacizumab + chemotherapy
Slide 30: Longer progression-free survival in patients with left-sided tumors
• Preliminary median PFS in left - sided tumors: 8.6 months • 9 left - sided tumor patients remain on therapy 30 Longer progression - free survival in patients with left - sided tumors As presented at ASCO GI 2024 2L CRC DKN - 01 + bevacizumab + chemotherapy
Slide 31: PFS still maturing with patients continuing on therapy
PFS still maturing with 6 patients continuing on therapy Rectal/rectosigmoid cancer subgroup 31 Preliminary median PFS : 9.4 months 6 - month PFS rate : 57.1% As presented at ASCO GI 2024 2L CRC DKN - 01 + bevacizumab + chemotherapy
Slide 32: Endometrial cancer development
DKN - 01 Endometrial cancer development
Slide 33: DKN-01 monotherapy overall response by DKK1 tumoral expression
Status Total CR PR SD PD NE ORR DCR DKK1 - high (≥18) * n=8 1 1 3 3 0 25% 63% DKK1 - low (<18) n=15 0 0 1 11 3 0% 7% Unknown n=6 0 0 5 1 0 0% 83% DKN - 01 monotherapy - overall response by DKK1 tumoral expression 33 CR PR SD SD PD PD PD PD PD PD PD PD PD PD PD PD PD SD SD SD — — PD PD SD SD SD SD —
Slide 34: Complete response in endometrial cancer patient on monotherapy
Complete response in endometrial cancer patient on DKN - 01 monotherapy 34 Maximum percent ecrease - 100% - 60% - 20% - 80% - 40% 0% 37.5 % 56 % tumor reduction CR Treatment: DKN - 01 monotherapy Patient: 60 yo female with recurrent endometrial cancer Prior treatment: radiation and chemotherapy poor
Slide 35: DKN-01 plus pembrolizumab endometrial cancer study
DKN - 01 plus pembrolizumab endometrial cancer study 35 * Move to Stage II based on ORR in Stage I 2 - 3 L E E C DKN - 01 + pembrolizumab Key eligibility criteria: • > 18 years of age • P athology - confirmed advanced or recurrent endometrial carcinoma • Non - endometrioid histologies included with
Slide 36: FL-301 and FL-302 Anti-Claudin18.2 antibodies
FL - 301 (NBL - 015) FL - 302 (NBL - 016) Anti - Claudin18.2 antibodies
Slide 37: The role of Claudin18.2
The role of Claudin18.2 37 Normal epithelial cells • Regulates barrier properties and contributes to cell - to - cell adhesion. • Expression very limited in normal tissue. • Typically buried in the tight junction complex of gastric mucosal cells. Cancer cells • In cancer, cells lose their polarity a
Slide 38: FL-301 is a potential best-in-class anti-Claudin18.2 antibody
FL - 301 (NBL - 015) is a potential best - in - class anti - Claudin18.2 antibody with enhanced tumor killing efficacy 38 FL - 301 CLDN18.2 Efficacy could extend to patients with lower CLDN18.2 expression that other currently used anti - CLDN18.2 antibodies. Engineered Fc High affinity Fab Higher af
Slide 39: FL-302 Claudin18.2-CD137 bispecific antibody program
FL - 302 (NBL - 016) Claudin18.2 - CD137 bispecific antibody program 39 FL - 302 CLDN18.2 - CD137 0 30 3000 2000 1000 0 Tumor volume (mm 3 ) Days post implantant Control Tumor free: 0% 5 mg/kg Tumor free: 67% Tetravalent construct СLDN18.2 - CD137 High affinit y to claudin18.2 СLDN18.2 CD137 CLDN18.
Slide 40: FL-501 Anti-GDF15 monoclonal antibody
FL - 501 Anti - GDF15 monoclonal antibody
Slide 41: The role of GDF15 in cancer
The role of GDF15 in cancer 41 41 Cancer cells GDF15 expression leads to a reduction in T cell infiltration and increase in Treg function. Cancer cell GDF15 GDF15 experessed by tumors is also able to drive cancer progression by promoting an immunosuppressive tumor microenvironment. Tumor
Slide 42: FL-501 mechanism of action
FL - 501 mechanism of action Cancer cells Inhibition of GDF15 by FL - 501 may promote immune stimulation in a broad range of cancers. T T reg Tumor FL - 501 is designed to block the immune inhibitory activity of GDF15. Cancer cell FL - 501 GDF15
Slide 43: Corporate
CORPORATE » & leaptherapeutics
Slide 44: Management team
Management team 44 Christine Granfield Vice president, head of regulatory affairs and quality Cyndi Sirard, MD Chief medical officer Jason Baum , PhD Chief scientific officer Walter Newman , PhD Senior research fellow Douglas Onsi President & chief executive officer M ark O’Mahony Chief manufacturin
Slide 45: Clinical milestones 2024-2025
DKN - 01 clinical milestones 2024 - 2025 45 Treatment: Indication: tislelizumab + chemotherapy bevacizumab + chemotherapy pembrolizumab Gastric cancer 1L Colorectal cancer 2L Endometrial cancer 2L Q2 2024 2025 Q3 Q4 Q1 Q2 Part C Data Initial Data Part B LPI Part B Data DisTinGuish DeFianCe Q3
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