Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Corporate Update (August 2023)
48 slides from Cardiff Oncology's corporate update, Aug 7, 2023
Slide 1: mCRC Program Update and Clinical Development Plan
AU GU ST 7 , 2 0 2 3 mCRC Program Update and Clinical Development Plan
Slide 2: Forward-looking statements
Forward-looking statements CERTAIN STATEMENTS IN THIS PRESENTATION ARE FORWARD-LOOKING within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as “anticipate,” "believe," "forecast," “estimated” and "intend" or other sim
Slide 3: We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024
PFIZER We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024
Slide 4: mCRC clinical development program agreed with FDA
mCRC clinical development program agreed with FDA • • • • • •
Slide 5: Annual eligible U.S. patients
5 3 Annual eligible U.S. patients (’000s)* 15 12 40 0 50 23 48
Slide 6: Line of Therapy, Ph2, Ph3 and investigator-initiated trials
Line of Therapy Ph2 Ph3 Investigator-initiated trials Trial Combination with:
Slide 7: Onvansertib clinical development plan in mCRC
CLINICAL FINDINGS FROM 2L Ph 1b/2 TRIAL SCIENTIFIC BASIS FOR CLINICAL FINDINGS CLINICAL DEVELOPMENT PATH FORWARD Onvansertib clinical development plan in mCRC
Slide 8: Onvansertib clinical development plan in mCRC
CLINICAL FINDINGS FROM 2L Ph 1b/2 TRIAL SCIENTIFIC BASIS FOR CLINICAL FINDINGS CLINICAL DEVELOPMENT PATH FORWARD Onvansertib clinical development plan in mCRC
Slide 9: Onvansertib properties and specificity
Onvansertib PROPERTIES SPECIFICITY • • •
Slide 10: 1st line and 2nd line RAS mutated mCRC
1st LINE 2nd Normal LINE RAS Mutated
Slide 11: 2nd line and 1st line RAS mutated mCRC
2nd Normal 1st LINE LINE RAS Mutated
Slide 12: MOA: RAS-mutations in mCRC
MOA 21 RAS-mutations in mCRC1
Slide 13: Trial design: enrollment criteria and efficacy endpoints
28 DAY CYCLE ENROLLMENT CRITERIA EFFICACY ENDPOINTS 1 2 3
Slide 14: Phase 1b and Phase 2 patient populations
PHASE 1b PHASE 2 ITT population (N) 50 68 Evaluable population* (N) 48 66 We enrolled 50 initial patients, and then an additional 18 patients, in our trial TOTAL
Slide 15: Bev exposed vs bev naïve patients
1st LINE 2nd Bev exposed vs bev naïve patients LINE
Slide 16: Bev naive patients achieved higher response rate with onvansertib+SoC
Bev naive patients achieved higher response rate with onvansertib+SoC Best Radiographic Response and Duration of Response* — 66 evaluable patients (as of June 16, 2023) ool alee Bevnaive | Bev exposed patients naive exposed N 66 15 51 ‘m= Comploto Response mm Partial Response sm. Stablo Disease ORR
Slide 17: Bev naive patients experienced more durable responses
Bev naive patients experienced more durable responses 8 os Swimmer plot* - 66 evaluable patients (as of June 16, 2023) é * o9 All Bev Bev a3 patients naive exposed ar 88 88 Pursued surgery / ablation 18% i205) 53% e's) 8% 51) — Initial PR at 8 week scan 9 8 1 Fa 8,88 38 g se + eon for Deon Initial P
Slide 18: Responses by KRAS variant
KRAS Variant CR+PR SD PD Total G12C G12D G12V G13D G12S G12A Q61H G13C
Slide 19: PFS exceeds historical controls for SoC, particularly in bev naive patients
PFS exceeds historical controls for SoC, particularly in bev naive patients Progression free survival* — 66 evaluable patients (as of June 16, 2023) — Bev naive — All patients — Bev exposed : 050) ~ 025 02s ‘i mPFS: 7.8 15.0 0.00: 0.00 7 é 5 ‘0 8 % & é 5 0 rs cy E Menths Menthe Characteristic N Even
Slide 20: Treatment-emergent adverse events
• • • • • • • TEAE GR1 GR2 GR3 GR4 TOTAL TEAE GR1 GR2 GR3 GR4 TOTAL Fatigue 24 22 7 0 53 78% Cough 11 0 0 0 11 16% Neutropenia 1 18 23 7 49 72% Pyrexia 8 1 1 0 10 15% Nausea 29 13 4 0 46 68% Dyspnea 7 3 0 0 10 15% Diarrhea 21 13 4 0 38 56% AST Increase 7 2 1 0 10 15% Leukopenia 9 14 5 1 29 43% Lymph
Slide 21: Onvansertib clinical development plan in mCRC
CLINICAL FINDINGS FROM 2L Ph 1b/2 TRIAL SCIENTIFIC BASIS FOR CLINICAL FINDINGS CLINICAL DEVELOPMENT PATH FORWARD Onvansertib clinical development plan in mCRC
Slide 22: Our findings establish the scientific basis of our bev naïve clinical finding
Our findings establish the scientific basis of our bev naïve clinical finding
Slide 23: Combination had superior anti-tumor activity in SW620 model
Tumor volume (mm 3 ) 0 10 20 30 0 500 1000 1500 2000 2500 SW620 (KRAS G12V) The combination had significant superior anti-tumor activity compared to the single agents
Slide 24: KRAS-mut tumors treated with onv + bev appear smaller and pale
KRAS-mut tumors from mice treated with onv + bev appear smaller and pale (less vascularized)
Slide 25: Hypoxia: a hallmark of cancer
Hypoxia: a hallmark of cancer In response to hypoxia, cancer cells activate the hypoxia- inducible factor (HIF) pathway, which can promote tumorigenesis through multiple means: + Angiogenesis * Cell proliferation and survival + Highly immunosuppressive and invasive tumor microenvironment + Hypoxia-i
Slide 26: PLK1 inhibition prevented hypoxia-induced HIF1a expression
PLK1 inhibition using siRNA against PLK1 (siPLK1) prevented hypoxia-induced HIF1a expression In 4 RAS-mutant CRC cell lines*, onvansertib inhibited hypoxia-induced HIF1a expression
Slide 27: New MOA inhibits a survival switch of tumorigenesis
This new MOA, which inhibits a “survival switch” of tumorigenesis, may underlie the increased efficacy observed clinically
Slide 28: Prior bev treatment modulates gene pathways that can confer resistance
Prior bev treatment modulates gene pathways that can confer resistance to bev and onvansertib + Aim: to identify potential mechanisms of treatment resistance in bev exposed KRAS-mutant mCRC patients + Method: KRAS-mutant mCRC patients 1* line treatment Q im FOLFOX (n=71) RNA-sequencing of lI FOLFOX
Slide 29: RAS-mutations in mCRC MOA
RAS-mutations in mCRC1 MOA 2 1 3
Slide 30: Onvansertib clinical development plan in mCRC
CLINICAL FINDINGS FROM 2L Ph 1b/2 TRIAL SCIENTIFIC BASIS FOR CLINICAL FINDINGS CLINICAL DEVELOPMENT PATH FORWARD Onvansertib clinical development plan in mCRC
Slide 31: FDA agreed with Cardiff Oncology's proposed 1st line clinical program
• • 2nd line mCRC 1st line mCRC • …and FDA agreed with Cardiff Oncology’s proposed 1st line clinical program FDA suggested we consider moving to a 1st line clinical development path…
Slide 32: Transition from 2L to 1L
• • • Clinical Commercial • • Transition from 2L to 1L Regulatory • • • •
Slide 33: Enrollment criteria and endpoints
ENROLLMENT CRITERIA ENDPOINTS Primary Secondary Benchmark of success
Slide 34: 2nd line and 1st line mCRC trials
2 nd Line mCRC 1 st line mCRC 2 nd Line mCRC 1 st line mCRC
Slide 35: Pfizer Breakthrough Growth Initiative and Ignite
BREAKTHROUGH GROWTH INITIATIVE • • • PFIZER PFIZER Ignite • •
Slide 36: We have multiple near-term clinical data read outs
We have multiple near-term clinical data read outs 15 line mCRC MPO AG NES randomized data readout data readout data readout SCLC data readout June 30, 2023 cash and investments $89.4M Net cash used in Operating Activities (Rolling two-quarter period ending June 30, 2023) $15.8M
Slide 37: We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024
PFIZER We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024
Slide 38: Appendix: Additional Ph 1b/2 Clinical Data
Appendix: Additional Ph 1b/2 Clinical Data
Slide 39: Expansion cohort replicated the improved responses in bev naïve patients
As an independent cohort in the Ph 1b/2 trial, the expansion cohort replicated the finding of improved responses from the bev naïve patients
Slide 40: Bev naive patients responded better than bev exposed
Bev naive patients responded better than bev exposed Swimmer plot* - 18 expansion cohort patients (as of June 16, 2023) All Bev Bev patients naive exposed Bev naive Pursued surgery / ablation 17% wis) 50%) 7% 0/18) ° Bev exposed TUORBSBRREERN 9@,09,,00009°
Slide 41: Expansion cohort patients replicated the prior bev naive finding
Expansion cohort patients replicated the prior bev naive finding Progression free survival* — 18 expansion cohort patients (as of June 16, 2023) — Bev naive — All patients — Bev exposed Probably of Suva 050] n= 000 i} io 8 Ey o 5 76 5 Ey Merits Months Characteristic N Event mPFS (95%Ci) Chaacteste N
Slide 42: mCRC Ph 1b/2 trial subgroup data compares favorably to SoC
mCRC Ph 1b/2 trial subgroup data compares favorably to SoC Objective response rates (%) and mPFS (mo) in our Ph1b/2 trial varied considerably by subgroup Bev naive Bev exposed Total Ph1b/2 (n=48) 82% (9 of 11) 14.0 mo 23% of patients 22% (8 of 37) 7.8 mo 77% of patients 35% (17 of 48) Ph2 Exp. (N=18
Slide 43: Bev naive patients experienced deeper tumor regression
Bev naive patients experienced deeper tumor regression Change in tumor size from baseline* — all doses (as of June 16, 2023) Bev naive Bev exposed Best response of: Median best response Median best response g =a % change: % change: 5 PR / o rogr 3 =s0 Alll patients -39% Allpatients -3% Ecoress E or
Slide 44: No single patient characteristic explains difference in response rates
No single patient characteristic explains the difference in response rates by prior bev status
Slide 45: Appendix: Additional Preclinical Data
Appendix: Additional Preclinical Data
Slide 46: Preclinical tumor models: KRAS G12D and G12C
0 5 10 15 20 -50 0 50 100 150 200 200 400 600 Treatment time (days) C1143 (KRAS G12D) ** *** 0 5 10 15 20 0 50 100 150 200 250 Treatment time (days) C1144 (KRAS G12C) ** **** Vehicle Onv+Irino Onvansertib Irinotecan
Slide 47: Preclinical tumor models: KRAS G13D, G12C and G12D
0 5 10 15 20 0 100 200 300 Treatment time (days) C1138 (KRAS G13D) ** *** 0 5 10 15 20 0 200 400 600 800 Treatment time (days) B8239 (KRAS G12C) *** *** 5 10 15 20 0 100 200 300 Treatment time (days) C1143 (KRAS G12D) * ****
Slide 48: Onvansertib inhibits vascularization in vitro
Onvansertib inhibits vascularization in vitro Tube formation assay: HUVEC endothelial cells seeded onto a 3D extracellular matrix form tube-like structures upon stimulation with the angiogenic factor VEGFA, simulating the formation of new blood vessels Treatment with onvansertib (25, 100 and 400nM)