Cardiff Oncology : Investor Presentation - January 15, 2021

Turning the Tide on Cancer

January 2021

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 similar terms or expressions that concern our expectations, strategy, plans or intentions. These forward-looking statements are based on our current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, our need for additional financing; our ability to continue as a going concern; clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; our ability to develop tests, kits and systems and the success of those products; regulatory, financial and business risks related to our international expansion and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that any of our technology or products will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in our Form 10-K for the year ended December 31, 2019, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and we do not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Investment Highlights

3rd Generation, 1st-in-class,

Oral PLK1 Inhibitor

Onvansertib overcomes the shortcomings of prior PLK inhibitors:

• Highly selective for PLK1
• Orally administered
• 24-hourhalf-life
• Flexible dose and schedule

Specifically targets a known mechanism of cell division that is required for tumor cell viability

Preliminary clinical data demonstrate the safety, tolerability and efficacy of onvansertib in combination with SOC across multiple indications

Strong Lead Program in KRAS-mutated mCRC

Supported by compelling preliminary clinical data from a Phase 1b/2 trial showing a ten-foldimprovement in ORR compared to SOC

Preclinical data support:

• MOA of synthetic lethality between KRAS mutant mCRC and PLK1 inhibition
• Synergy with irinotecan and 5-FU

First Indication: 2nd line treatment in patients who have failed 1st line treatment with FOLFOX with/without bevacizumab

FDA Fast Track Designation

Integrated Biomarker

Strategy

Circulating Tumor DNA: changes in KRAS mutational burden in blood are predictive of subsequent tumor shrinkage (mCRC)

Circulating Tumor Cells: changes are predictive of overcoming anti- androgen resistance (mCRPC)

Circulating Tumor DNA: changes are predictive of decreases in leukemic bone marrow cells (AML)

Diversified Pipeline Across

Numerous Cancers

Clinical data from ongoing trials support the use of onvansertib in combination regimens across numerous aggressive cancers:

• mCRC Phase 1b/2 trial
• mCRPC Phase 2 trial
• AML Phase 2 trial

Potential expansion opportunities:

• Chronic myelomonocytic leukemia
• Pancreatic cancer
• Triple negative breast cancer
• Lung cancer
• Ovarian cancer

PLK: Polo-like Kinase; SOC: Standard-of-care; ORR: Overall response rate; MOA: Mechanism of action; mCRC: metastatic colorectal cancer;

mCRPC: metastatic castration resistant prostate cancer; AML: Acute myeloid leukemia

2020 Corporation Presentation I 3

Experienced Management Team With Drug Development and Biomarker Technology Expertise

	Mark Erlander, PhD			Vicki Kelemen
	Chief Executive Officer			Chief Operating Officer

Brigitte Lindsay

Vice President of Finance

2020 Corporation Presentation I 4

Onvansertib

3rd generation, 1st in class, oral and highly selective PLK1 inhibitor addressing unmet needs across a broad range of cancer indications

PLK1 is a Proven Therapeutic Target that is Overexpressed in Most Cancers

• PLK1 is a serine/threonine kinase and master regulator of cell-cycle progression
• PLK1 controls G2/mitosis (G2/M) checkpoint
• Inhibition of PLK1 causes mitotic arrest and subsequent cell death
• Emerging data demonstrate that PLK1 is also a key regulator of cellular functions beyond mitosis that are essential for tumor growth:
• • Biosynthesis of DNA
  • DNA Damage Response

1Zitouni et al., Nat Rev Mol Cell Biol. 2014 Jul;15(7):433-52; PLK1: Polo-like kinase 1

Inhibition of PLK1 causes mitotic arrest

and subsequent cell death1

2020 Corporation Presentation I 6

PLK1-Specific ATP Competitive Inhibitor1

Biochemical Profile

Profile Characteristics

Co-crystal of Onvansertib with PLK1

Enzyme	IC50 (μM)
PLK1	0.002
PLK2	>10
PLK3	>10
CK2	0.4
FLT3	0.4
CDK1/CycB	3.8
42 additional kinases in house	>10
>190 additional kinases in the	>10
Millipore panel

Small Molecule

Formulation

Plasma Protein Binding

Metabolic

Overview

Pharmacokinetics3

MW 648.60 Daltons

5mg and 20mg oral gelcaps

95% at 10μM and 91% at 50μM

Moderate intrinsic clearance (9.3 mL/min/kg)1

2 metabolites identified in metabolic profiling in low quantities (parent drug accounted for 93% of total drug-related material)1

No Cytochrome P450 inhibition at therapeutic concentrations2

Systemic exposure of drug increased with dose, as shown by an increase in Cmax and AUC0-24

Tmax is approximatively 3h Half-life is approximately 24h

Substituted by His in

PLK2 and PLK3

•

Onvansertib •

•

1Valsasina Mol Cancer Ther 2012

A selective, ATP competitive PLK1 inhibitor

Selectivity is driven by polar interaction with the side chain of Glu140 of PLK1 Interaction is hampered in both PLK2 and PLK3 where Glu140 is replaced by histidine

2020 Corporation Presentation I 7

Onvansertib has Optimal Drug Properties and Synergistically Combines with Standard-of-Care Therapies

Optimal Drug Properties

Synergistic in Combination with Standard-of-

Care Chemo and Targeted Therapies

Demonstrated

Safety and

Tolerability

Predictive

Biomarker

Oral

Administration

High Selectivity

For PLK1

Onvansertib

24-hourHalf-life

Synergistic in

Combination

Flexible Dosing

and Scheduling

Ideal

Pharmacokinetics

Taxol®

(paclitaxel)

Venclexta® (venetoclax)

Camptosar®

(irinotecan)

5-FU

Beleodaq®

(belinostat)

Zytiga®

(abiraterone)

Onvansertib

Velcade®

(bortezomib)

Avastin®

(bevacizumab)

Cytarabine

Doxorubicin

Cisplatin

Gemzar®

(gemcitabine)

2020 Corporation Presentation I 8

Second-Line Treatment of KRAS-Mutated mCRC

Phase 1b/2 open-label trial of onvansertib + FOLFIRI/bevacizumab

Trial Sites: USC Norris Comprehensive Cancer Center; Mayo Clinics (Arizona, Rochester, Jacksonville), Kansas University Medical Center, CARTI Cancer Center

Principal Investigator: Dr. Heinz-Josef Lenz

New Second-Line Therapies are Needed to Improve Response and Increase Progression-Free Survival

50% of patients with mCRC	Prognosis is poor with a five-	Other drugs currently in development
have a KRAS mutation	year survival rate of 10%	do not address the most prevalent
		KRAS mutations in mCRC

4%

Response

to SOC

5.5

Months

PFS

Significant limitations to standard-of-care (SOC)

Historically, second-linestandard-of-care treatment in KRAS-mutated mCRC has had an overall response rate of 4% and progression-free survival (PFS) of 5.5 months1

1Kubicka et al, Annals of Oncology 2013; 2342-2349; mCRC: Metastatic colorectal cancer

2020 Corporation Presentation I 10

KRAS is a Pivotal Diagnostic Biomarker in the CRC Treatment Paradigm

• KRAS-mutatedpatients do not benefit from anti-EGFR agents:
• • No increase in OS, PFS and ORR was observed in KRAS mutant patients treated with EGFR inhibitors vs control arm1,2
  • The use of anti-EGFRs is therefore limited to KRAS wild-type patients
• Mutations in KRAS represent also the most frequent mechanism of resistance to anti-EGFRs (i.e. cetuximab)

KRAS Mutant	KRAS Wild-type	Treatment Paradigm
			mCRC
		KRAS	KRAS
		Mutant	Wild Type
		Chemotherapy ±	Chemotherapy +
		bevacizumab	EGFR inhibitor

1Karapetis et al., NEJM 2008;359:1757-1765;2Amado et al., JCO 2008, 26:1626-1634

2020 Corporation Presentation I 11

Second-line Treatment: Real World Utilization in the US

Flatiron Health Data

255

Cancer clinics representing

1.7 million active cancer patients

14,315

Colorectal cancer patients

7,034

Colorectal cancer patients who

receive second line therapy

Source: Hess, L. International Journal of Colorectal Disease; 2019. Data is limited to limited to second-line regimens used in >1% of the cohort. FOLFOX:

fluoropyrimidine, leucovorin, oxaliplatin. FOLFIRI: fluoropyrimidine, leucovorin, irinotecan, FOLFOXIRI: fluoropyrimidine, leucovorin, irinotecan, oxaliplatin

Denotes combination with bevacizumab

Denotes combination with other antiangiogenics

2020 Corporation Presentation I 12

New Second-line mCRC Treatment is an Unmet Need

Outcomes for patients in the 2nd line setting is poor

• Efficacy of FOLFIRI: 4% ORR and 2.5 months PFS1
• Addition of bevacizumab to FOLFIRI improves outcomes2
• However, while KRAS WT patients benefit from the addition of bevacizumab, there was no statistically significant improvement in OS for KRAS-mutant patients3

KRAS	Treatment	ORR	PFS	HR and significance	OS	HR and significance of
(months)	of PFS	(months)	OS
	FOLFIRI	5%	4.5	HR=0.61	11.1	HR=0.61
KRAS WT				(95 % CI 0.49-077)		(95 % CI 0.53-0.90)
FOLFIRI + Bev	7%	6.4	15.4
	P <0.0001	P=0.0052
KRAS	FOLFIRI	3%	4.1	HR=0.70	10	HR=0.92
			(95 % CI 0.56-0.89)		(95 % CI 0.71-1.18)
MUTANT	FOLFIRI + Bev	4%	5.5	10.4
P = 0.0027	P=0.4969

1Tournigand et al., JCO 2004;22(2):229-3; 2Bennouna et al., Lancet Oncol. 2013; 14(1):29-37; 3Kubicka, S, Annals of Oncology 2013, 24:2342-2349; CI:	2020 Corporation Presentation I 13
confidence interval, HR: hazard ration, ORR: objective response rate, PFS: progression-free survival, OS: overall survival, WT: wild-type, MUT: mutant

Magnitude of Response with Other Antiangiogenic Therapy

The anti-angiogenic agents aflibercept and ramucirumab have been approved in combination with chemotherapy in 2nd line treatment, although they are used to a much lesser extent than bevacizumab

Trial	Agent/ARM	Patients	ORR	95% CI of ORR (%)
VELOUR Sub-group1 (received	FOLFIRI +	643 (325 FOLFIRI	11.8%	6.7 - 16.9
first line therapy and
aflibercept	+aflibercept)
bevacizumab)
RAISE2	FOLFIRI +	1361	13.4%*	10.7 - 16.6
ramucirumab
* 20% of patients were Asian, which has higher response rate

1Van Cutsem et al., Target Oncology 2016, 11:383-4002Tabernero et al., Lancet Oncology 2015;16:499-508

2020 Corporation Presentation I 14

Synthetic Lethality: Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK1

The output of the RAS-mutated pathway activates PLK1, which is inhibited by onvansertib

Onvansertib Addresses KRAS Mutation		Cell Viability in Onvansertib-Treated KRAS Mutant
Subtypes in mCRC		and Wild Type Isogenic CRC Cells

		2%	1%
	6%	6%
8%				39%

18%

22%

G12D G12V G13D G12C G12S G12A Q61H G12R

PLK1: Polo-like Kinase 1; mCRC: Metastatic colorectal cancer

2020 Corporation Presentation I 15

PLK1 and RAS Cooperative Relationship

RAS activates PLK1 through a MEK/ERK-independent mechanism

The downstream target of KRAS, pCRAF, localizes to the mitotic spindle poles at mitosis where it interacts with PLK1 and promotes PLK1 activation, leading to mitosis and tumor progression1

Data suggest that KRAS-activated cells are dependent on PLK1 for their proliferation and survival and inhibition of PLK1 by onvansertib could inhibit tumor growth

1Mielgo et al., Nat. Med. 2011; 17(12):1641-5

RAS

RAF

P

P

MEK

P

ERK

Onvansertib

P

CRAF PLK1

PLK1 Activity

Mitotic Progression

Proliferation/Survival

2020 Corporation Presentation I 16

Synergy: Onvansertib in Combination with SOC Irinotecan and 5-FU

Onvansertib works synergistically in combination with standard-of-care FOLFIRI (irinotecan and 5-FU)

HCT-116 (with G13D KRAS mutation)

Synergy in Combination with Irinotecan		Synergy in Combination with 5-FU

2020 Corporation Presentation I 17

PLK1 Regulates DNA Damage Response1,2

DNA Damaging		G2/M Arrest
Agents

DNA Damage

Response

(DDR) arrests cells at G2/M checkpoint

• Irinotecan

• 5-FU

1van Vugt & Yaffe, Cell Cycle 2010 9:2097-2101;2van Vugt et al., 2010, PLoS 8:1-19

Mitosis

1. Checkpoint adaptation
2. PLK1 inhibits DDR, induces mitotic entry for tumor cells & cell division

Cell Death

1. Keeps tumor cells in G2/M arrest leading to apoptosis
2. For cells that escape, mitosis is blocked, also leading to apoptosis

2020 Corporation Presentation I 18

Phase 1b/2 Open Label Trial of Onvansertib + FOLFIRI/bevacizumab

Trial Design

					1 CYCLE = 28 Days
		Treatment Course = 14 Days				Treatment Course = 14 Days
1	2	3	4	5	6 - 14	1	2	3	4	5	6 - 14
Onvansertib					Onvansertib
FOLFIRI + bevacizumab				FOLFIRI + bevacizumab

Efficacy Endpoints

• Overall response in patients who receive ≥1 cycle (2 courses) of treatment
• Progression-freesurvival (PFS)
• Decreases in KRAS mutation burden and response to treatment

What is Clinical Trial Success

• ≥5 of 26 (~20%) patients achieve clinical response confirmed by radiographic scan
• Achieve median progression-free survival of ≥ 6 months

2020 Corporation Presentation I 19

Phase 1b Enrollment and Patient Baseline Characteristics

Dose Escalation Patient Cohorts

(as of 06-Jan-2021)

Number of	Dose Level 0	Dose Level +1	Dose level +2
Onvansertib	Onvansertib	Onvansertib
patients (N)
12 mg/m2	15 mg/m2	18 mg/m2
Completing 1st
6	6	6
cycle
Currently on	0	3	2
Treatment

• Phase 1b: 3+3 dose escalation design to assess the safety of the combination and identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of onvansertib

Total patients N=18	Median [range] or n (%)
Age (years)	59 [37-83]
Sex
Male	8 (44%)
Female	10 (56%)
ECOG
0	8 (44%)
1	10 (56%)
Primary tumor site
Colon	9 (50%)
Rectum	7 (39%)
Unknown	2 (11%)
Liver metastasis
None	7 (39%)
Liver and other	8 (44%)
Liver only	2 (17%)
Number of metastatic organs
1	7 (39%)
≥2	11 (61%)
Prior Bevacizumab treatment
Yes	13 (72%)
No	5 (28%)

2020 Corporation Presentation I 20

Phase 1b Safety Assessment

Most Common Treatment-Emergent AEs

Adverse Events (AEs)	Grade	Grade	Grade	Grade	All	•	5 patients had G4 adverse events:
	1	2	3	4	Grades		-	1 patient had a G4 neutropenic fever at dose level 12 mg/m2
Fatigue	4	7	1	0	12
	-	1 patient had a G4 neutropenia at dose level 15 mg/m2
Nausea	8	3	1	0	12
	-	3 patients had a G4 neutropenia dose level 18 mg/m2
Neutropenia	1	2	4	4	11
Diarrhoea	7	2	0	0	9	• The onvansertib RP2D was confirmed at 15 mg/m2
Alopecia	6	1	0	0	7
Abdominal pain	1	4	1	0	6	•	The combination regimen was well tolerated:
Anaemia	4	1	0	0	5
WBC decrease	2	3	0	0	5
	-	Of all AEs only 8% (17/202) were G3/G4
Vomiting	3	1	1	0	5
	-	The only G3/G4 AE reported in ≥2 patients were
Stomatitis	4	1	0	0	5
		neutropenia (n=8); which was managed by dose delay,
Thrombocytopenia	2	2	0	0	4
		growth factor and/or discontinuation of the 5-FU bolus;
Mucosal inflammation	1	2	0	0	3
		no patients went off trial due to neutropenia
Dyspepsia	3	0	0	0	3
ALT increased	2	1	0	0	3	•	No major or unexpected toxicities were attributed to
Abdominal distension	3	0	0	0	3
	onvansertib
Back pain	3	0	0	0	3
Epistaxis	3	0	0	0	3

n=number of patients (total N=18); WBC=white blood cells; ALT= alanine aminotransferase

2020 Corporation Presentation I 21

Phase 1b Preliminary Efficacy

18 mg/m2 15 mg/m2 12 mg/m2

Treatment Response and Duration

Changes in Tumor Size From Baseline

						(as of 06-Jan-2021)				100									01-003
															→ Treatment ongoing
										weeks													02-004
	8weeks		weeks weeks	weeks	weeks weeks weeks		80
			40
01-007			16	24	32			48	56	64	Reason for discontinuation	change% in target fromlesionsbaseline									PD	02-005
														60
02-008																Stable Disease (SD)									01-011
01-006																Curative surgery											01-006
01-003							⊗									Patient/MD decision		40
02-004																Treatment-unrelated AE		20									01-007
02-005															⊗										02-008
01-010															Radiographic assessment		0								SD
		⊗																			01-010
01-011
		→												Partial Response (PR)		-20
01-019
02-012											→				Progressive Disease (PD)		-40								PR	02-012
														-60
01-013					→									Onvansertib dose adjustments										01-013
02-016																									01-014
01-014																		Baseline	weeks	weeks	weeks	weeks	weeks	weeks	weeks	weeks
																Dose level -1		02-016
02-015																Dose level +1
0	28	56	84	112	140 168 196 224	252 280 308 336	364 392 420	448 476				8	16	24	32	40	48	56	64
	Received bevacizumab in 1st line
						Days of treatment

• 18 patients were treated in Phase 1b (6 patients at each dose level); 2 patients discontinued during cycle 1; 2 patients have completed cycle 1 but have not had their first 8-week scan
• 12 of 14 (86%) patients evaluable for efficacy* achieved a clinical benefit (SD + PR)
• • 5 (36%) patients have achieved a partial response (PR)
  • • 4 patients had a confirmed PR; 1 patient went on to have curative surgery
    • 1 patient with non-confirmed PR went off study following PR due to treatment-unrelated AE
  • Time to achieving a PR ranges from 2 to 6 months in patients on treatment

*completed at least 1 cycle of treatment and had radiographic scan or progressed within 8 weeks while on treatment

2020 Corporation Presentation I 22

KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses

% KRAS MAF Decrease Following 1 Treatment Cycle

KRAS MAF Over Time

				PR				SD			PD
MAF at baseline	0
% change in KRAS Cycle 2 Day 1 from	-50
											75% decrease
-100
	-004-010-005-007-013	-016-019-012-011-006	-008-015
	02	01 02	01	01	02 01	02	01	01	02	02

	50
(%)	40
MAF	30
KRAS	20
10

0

C1D1C1D7C2D1C3D1C4D1C5D1C6D1C7D1C8D1C9D1

Visit

02-004 KRAS G13D
02-005 KRAS G12V			PR
01-010 KRAS G12A
01-007 KRAS G12D
01-013 KRAS A146T
01-006 KRAS G12V
01-011 KRAS G12D
02-012 KRAS G12V			SD
02-016 KRAS G12D
01-019 KRAS G12D
02-008 KRAS G12C			PD
02-015 KRAS G12D

• KRAS MAF was measured by digital droplet PCR (ddPCR) at baseline (Cycle 1 Day 1, pre-dose) and on-treatment (Day 1 of Cycles 2 to 9)
• 12 of 14 patients had a KRAS mutation detected by ddPCR at baseline (all had a KRAS mutation detected by NGS)
• Clinical responses were observed across different KRAS mutations, including the 3 most common in CRC (G12D, G12V, G13D)
• The greatest decreases in KRAS MAF after 1 cycle of treatment were observed in patients achieving a PR (all patients had >75% decrease) and SD (4 of the 5 patients had reductions >75%), the 2 patients who progressed showed a more modest decrease in KRAS MAF (-55% and -26%)

PR: partial response, SD: stable disease, PD: progressive disease; CXD1: Cycle X Day 1

2020 Corporation Presentation I 23

Conclusions

• Safety Assessment:
• • The combination of onvansertib and FOLFIRI/Bev is well-tolerated
  • Onvansertib RP2D was established at 15 mg/m2
• Preliminary Efficacy:
• • 12 of 14 (86%) patients evaluable for efficacy achieved a clinical benefit (SD + PR)
  • 5 (36%) patients achieved a partial response (PR), including 4 confirmed PRs; 1 patient proceeded to curative surgery
• KRAS Mutant Allelic Frequency (MAF) Biomarker:
• • Clinical responses were observed across different KRAS variants, including the 3 most common in CRC
  • Patients achieving a PR or SD showed the greatest decreases in plasma mutant KRAS after one cycle of therapy
• Phase 2:
• • Further assess the safety and efficacy of onvansertib at the RP2D in combination with FOLFIRI + bevacizumab
  • Evaluate the value of KRAS liquid biopsy to predict treatment response

2020 Corporation Presentation I 24

KRAS-Mutated mCRC Expanded Access Program (EAP)

• Program initiated in June 2020 and first patients were enrolled in July / August
• • Treatment regimen: onvansertib 15 mg/m2 + FOLFIRI/bevacizumab
• Eligibility criteria includes:
• • Patients not eligible for clinical trial (including patients who have received multiple lines of treatment)
  • Patients who have previously been treated with FOLFIRI (with or without bevacizumab)
• Findings from first 9 patients enrolled in July / August 2020:
• • 6 of 9 (66%) patients have shown tumor shrinkage and remain on treatment to-date with durable response lasting ~6 months (all 9 patients received prior FOLFIRI-based regimen)
  • Of the 6 patients showing tumor shrinkage, 5 different KRAS mutations were represented (G12A, G12C, G12V, G13D, A146T)
  • Changes in KRAS mutant allelic frequency (MAF) in patients after the first cycle of treatment are predictive of subsequent tumor shrinkage (as seen in the clinical trial)
  • No serious adverse effects (SAEs) have been reported to-date

2020 Corporation Presentation I 25

Catalysts and Milestones: KRAS-Mutated mCRC

Positive Phase 1b/2 results may provide an opportunity for a Phase 2b registrational trial

May 2020: Fast Track	September 2020: ESMO	January 2021: ASCO-GI	Q1 2021: FDA meeting to
discuss regulatory path
Designation	presentation	presentation
(anticipated)

mCRC: Metastatic colorectal cancer

2020 Corporation Presentation I 26

Metastatic Castration-Resistant Prostate Cancer

Phase 2 open-label trial of onvansertib + abiraterone

Trial Sites: Beth Israel Deaconess, Dana Farber, Mass General Hospital

Principal Investigator: Dr. David Einstein

New Therapeutic Options are Needed to Overcome Resistance to SOC Androgen Receptor Signaling Inhibitors (ARSi)

Resistance develops to treatment with standard	ARSi's offer a median overall survival	No effective treatment options are
of care ARSi's within 9-15 months1	(mOS) benefit of only ~4 months1	available for the up to 40% of mCRPC
		patients with an AR-V7 mutation2

9-15

Months until

ARSi resistance

~4

Month mOS

benefit

Limited options for patients once resistant to abiraterone

New treatment options are needed to extend the duration of response to ARSi's and increase overall survival

1Antonarakis, Emmannel - Current Understanding of Resistance to Abiraterone and Enzalutamide in Advanced Prostate Cancer; Clinical Advances in Hematology & Oncology - May 2016 - Volume 14, Issue 5; 2Armstrong et al., 2019, JCO 37: 1120-1129; SOC: Standard-of-care; mCRPC: Metastatic castration resistant prostate cancer

2020 Corporation Presentation I 28

Onvansertib Extends the Response to Androgen Receptor

Signaling Inhibitors

Onvansertib works synergistically in combination with abiraterone (Zytiga®) and significantly increases mitotic arrest

Onvansertib + Abiraterone (Zytiga®) Demonstrate

Synergy in mCRPC model (C4-2)1

Onvansertib + Abiraterone (Zytiga®) Significantly

Increase Mitotic Arrest1

1Patterson & Yaffe, 2019, MIT; mCRPC: Metastatic castration resistant prostate cancer

2020 Corporation Presentation I 29

Phase 2 Open Label Trial in of Onvansertib + Abiraterone

Disease Control Assessed by PSA Stabilization

Trial Design:

	Dosing Schedule		Duration	Efficacy Endpoint
Cohort A (n = 24)
Onvansertib 24mg/m2	Days 1-5(21-day cycle) + Zytiga® (Abiraterone)	4 Cycles = 12 Weeks	Disease Control
Cohort Closed	(PSA Stabilization or Decline)
Cohort B (n = 32)	Onvansertib 18mg/m2	Days 1-5(14-day cycle) + Zytiga® (Abiraterone)	6 Cycles = 12 Weeks	Disease Control
(PSA Stabilization or Decline)
Cohort C (n = 32)	Onvansertib 12mg/m2	Days 1-14(21-day cycle) + Zytiga® (Abiraterone)	4 Cycles = 12 Weeks	Disease Control
(PSA Stabilization or Decline)

Eligibility Criteria

Initial resistance to Zytiga; 2 consecutive rises in PSA levels

Efficacy Endpoint:

Internationally Recognized Prostate Cancer Working Group

• Primary: disease control evaluated as PSA decline or stabilization (PSA rise <25% over baseline)

What is Clinical Trial Success

• ~30% patients achieve primary efficacy endpoint of disease control at 12 weeks (PSA stabilization or decrease); confirmed by radiographic scan
• Achieve median radiographic PFS of ≥6 months

Note: radiographic assessment by RECIST v1.1 [CR = disappearance of all target lesions, PR = ≥30% decrease, PD = ≥20% increase, SD = does not

meet criteria for PR nor PD]; mCRPC: Metastatic castration resistant prostate cancer; PSA: Prostate specific antigen; PFS: Progression-free survival

2020 Corporation Presentation I 30

Patient Baseline Characteristics and Enrollment Status

Patient Baseline Characteristics

Total patients N=39	Median [range] or n (%)
Age in Years	72 [54-87]
Nonwhite Ethnicity	5	(13%)
ECOG
0	34 (87%)
1	5	(13%)
Years Since Diagnosis	5	[1-18]
Grade Groups 4 and 5	24 (62%)
De Novo Metastatic Disease	13 (33%)
Presence of Bone Metastasis	33	(85%)
Presence of Visceral Metastasis	13	(33%)
Baseline PSA, ng/mL	12.5 [0.6-224]
AR-V7+ at Baseline*	9	(23%)
Baseline CTC Count per mL of blood**	2.2 [0-87]

ECOG: Eastern Cooperative Oncology Group, AR-V7: androgen receptor variant

7, CTC: circulating tumor cells

*AR-V7 status was evaluated using the EPIC and Johns Hopkins University testing platforms **CTC count was performed by EPIC

Enrollment as of October 16th, 2020

Number of patients (N)	Arm A	Arm B	Arm C
Treated	24	11	4
Currently on Treatment	1	1	4
Completing 12-weeks	14	8	3
Discontinued before 12 weeks	10	2	0
Progressive Disease (PD)	3	1	0
Adverse Event	5	1	0
Withdrew Consent	2	0	0
Patients evaluable for efficacy	17	9	3
(completed 12 weeks + PD)

2020 Corporation Presentation I 31

Phase 2 Data Demonstrate the Safety and Efficacy of Onvansertib in mCRPC

Safety Assessment

Adverse events	Grade 1	Grade 2	Grade 3	Grade 4	All grades
Total Patients N=39
Anemia	10	5	1		16
Thrombocytopenia	11	1		1	13
Fatigue	10	2			12
Neutropenia	1	1	7	3	12
Hypophosphatemia	3	3	4		10
WBC decrease	2	2	3	2	9
Back pain	2	3			5
Hypokalemia	3	1	1		5
Constipation	4	0			4
Nausea	3	1			4

• Most frequent Grade 3 and 4 adverse events (AEs) were expected, on-target, hematological associated with onvansertib mechanism of action
• Hematological AEs were reversible and effectively managed by dose delay, dose reduction and/or growth factor support

2020 Corporation Presentation I 32

Phase 2 Data Demonstrate the Efficacy of Onvansertib and and Durability of Response Including Patients with AR Alterations

Efficacy Evaluation at 12-Weeks

Total Patients Evaluable N=29	Arm A	Arm B	Arm C
Evaluable for efficacy*	17	10	4

Treatment Response and Duration for Patients

Completing 12 Weeks of Treatment

Completed 12-week treatment	14	8	4
Progressed within 12 weeks	3	2	0
Disease control**	5 (29%)	3 (30%)	3 (75%)
Radiographic stable disease	9 (53%)	5 (50%)	4 (100%)
Durable response (>7 months)	4 (23%)	4 (40%)	NA

• Completed 12 weeks of treatment or progressed within 12 weeks
• Defined as PSA stabilization or decline (PSA rise <25% over baseline)

Arm B (5+9) Arm C (14+7)

Arm A (5+16)

03-043

01-044

02-045

02-046

01-025

01-026

03-030

01-024

02-041

01-033

03-039

02-042

01-014

03-017

03-037

01-021

02-036

03-013

02-003

03-004

02-007

03-023

03-009

01-019

03-028

02-020

months	months months1		year
			year
			.
3	6	9		5
	1

→

→

→

→

0	100	200	300	400	500	600
		Days of treatment

PSA endpoint

Partial response

Stable disease Radiographic Progressive disease assessment

Physcian decision		Reason for
Patient decision		discontinuation
Adverse event*		other than PD

• Ongoing

Transitioned to Arm B

AR-V7+

AR T878A AR alterations AR Amplification

202020CorporationPresesentationI I3333

Phase 2 Data Demonstrate the Efficacy of Onvansertib and Durability of Response Including Patients with AR Alterations

Treatment Response and Duration for Patients

Completing 12 Weeks of Treatment

Efficacy in patients with AR alterations:

• 8 of the patients evaluable for efficacy had at least 1 AR alterations: AR-V7+ (n=6), AR T878A mutation (n=2) and/or AR amplification (n=3)
• 3 (37%) patients achieved disease control
• 4 (50%) patients had radiographic stable disease
• 3 patients had durable responses (range 7-9 months)

*AR-V7 status was evaluated using the EPIC and Johns Hopkins University testing platforms. Genomic profiling of circulating tumor DNA was performed using Gardant360® test

Arm B (5+9) Arm C (14+7)

Arm A (5+16)

03-043

01-044

02-045

01-025

01-026

03-030

01-024

02-041

01-033

03-039

02-042

01-014

03-017

03-037

01-021

02-036

03-013

02-003

03-004

02-007

03-023

03-009

01-019

03-028

02-020

months	months	months year	.
					year
	6			5
3	9	1	1

→

→

→

0	100	200	300	400	500	600
		Days of treatment

PSA endpoint
Partial response		Radiographic
Stable disease
	assessment
Progressive disease
Physcian decision		Reason for
Patient decision		discontinuation
Adverse event*		other than PD

• Ongoing

Transitioned to Arm B

AR-V7+

AR T878A AR alterations AR Amplification

2020 Corporation Presentation I 34

Onvansertib-Induced Circulating Tumor Cell Decrease is Associated with Progression-Free Survival

Circulating tumor cell (CTC) count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is a

prognostic factor for survival in CRPC - conversion from unfavorable to favorable is associated with improved survival

Percent Change in CTC: 12-Weeks vs Baseline in Patients with Unfavorable CTC Level at Baseline

At baseline, 27 (73%) of 37 patients had unfavorable CTC count; 10 were analyzed following 12 weeks of treatment:

• 5 (50%) patients had an ≥80% CTC decrease, including 2
  AR-V7+ patients (01-024 and 01-025)
• 4 (40%) patients converted from unfavorable to favorable CTC level, including 3 patients with no detectable CTC
• Median time on treatment was 9.2 months for patients with CTC decrease (n=5) vs 4.9 months for patients with CTC increase (n=5)

CRPC: Castration resistant prostate cancer

2020 Corporation Presentation I 35

Identifying an Onvansertib-Abiraterone Response Gene Signature

Onvansertib/Abiraterone

• Synergy study	Abiraterone induces expression of	Identification of an
• RNA-sequencing	mitotic genes in prostate cancer	Abi/Onv synergy gene signature
cells synergistic for Onv+Abi

	Identified 4 molecular subtypes:	Abi/Onv synergy gene signature is
	• Luminal A	enriched in the Basal subtype, a subtype
Transcriptome analysis of 32,000	• Luminal Proliferating	representing ~30% of CRPC patients and
• Basal	associated with lower response to
prostate cancer specimens	• Basal Immune	androgen deprivation therapy (ADT)

Currently analyzing archived	Transcriptome analysis with
tissue from patients enrolled	Correlate clinical response with
in the trial	Decipher Biosciences	Basal molecular subtype

2020 Corporation Presentation I 36

Catalysts and Milestones: mCRPC

Positive Phase 2 results may provide an opportunity for a Phase 2b registrational trial

October 2020: Prostate	February 2021: ASCO-	April 2021: AACR	Q3 2021: FDA meeting to
Cancer Foundation (PCF)	GU presentation (planned)	presentation (planned)	discuss regulatory
			pathway (anticipated)

2020 Corporation Presentation I 37

New Clinical Programs Planned

Chronic Myelomonocytic Leukemia (CMML) Pancreatic Ductal Adenocarcinoma (PDAC)

Phase 2 Study to Evaluate the Safety and Efficacy of Onvansertib in RAS- Pathway Mutant CMML

Study Rationale

• Proliferative CMML is enriched for activating RAS pathway mutations such as NRAS, KRAS, CBL, PTPN11 and NF1, all of which have been associated with adverse outcomes
• RAS pathway mutations drive proliferative CMML via a novel RAS-KMT2A-PLK1 axis, which can be therapeutically targeted with PLK1 inhibitors
• In-vitroand in-vivo experiments with onvansertib as a single agent have shown a dose-dependent inhibition of CMML cell growth, with improved cell differentiation

Activating RAS Pathway Can Be Therapeutically

Targeted with PLK1 Inhibitors

PLK

1

2020 Corporation Presentation I 39

Phase 2 Two-Arm Randomized Trial of Onvansertib +/- Decitabine in RAS-Pathway Mutated CMML

Determine the safety and efficacy of onvansertib, a novel oral PLK1 inhibitor in RAS-pathway mutant chronic myelomonocytic leukemia

Trial Design:

	Dosing Schedule		Duration	Efficacy Endpoint
Two Arms:
Onvansertib 15 mg/m2	Days 1-14	3 cycles monotherapy (option to add	Interim analysis of first 18 patients after
Arm A (n=32) Treatment Naïve	decitabine at cycle 4 if lack of efficacy
(21-day cycle)		3 cycles to evaluate objective response
Arm B (n=32) Relapsed/Refractory		with single agent)

Eligibility Criteria:

• Newly diagnosed or relapsed/refractory to prior therapy
• RAS pathway mutant: NRAS, KRAS, PTPN11, CBL and NF1 with frequency allele of ≥5%

Efficacy Endpoint:

• Rate of complete remission (CR)

What is Clinical Trial Success

• Achieve ≥25% CR rate in treatment naïve cohort
• Achieve ≥12.5% CR rate in the relapsed and refractory cohort

402 2020CorporationPresesentationI I40

Phase 2 Study of Onvansertib in Combination with 5-FU and Nal-IRI for Second Line Treatment of KRAS-Mutated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

Study Rationale

• KRAS is the most common oncogene mutated in pancreatic adenocarcinoma, which is present in ~95% of tumors
• Mutant KRAS is essential for PDAC growth, where the constitutive activated RAS proteins contribute to tumorigenesis, treatment resistance and metastases
• No effective RAS inhibitors have been approved for the treatment of KRAS-mutated pancreatic cancer

Metastatic Pancreatic Cancer Patients

Have Poor Outcomes

• Significant need for new effective second line treatment option

2020 Corporation Presentation I 41

Phase 2 Open Label Trial of Onvansertib + 5-FU and Nanoliposomal Irinotecan in KRAS-Mutated PDAC

Trial Design (~40 patients):

1 CYCLE = 14 Days

Treatment Course (Days)

1

2

3

4

5

6 - 14

Onvansertib 15 mg/m2

5-FU + Nanoliposomal Irinotecan (nal-IRI)

Eligibility Criteria

• Prior abraxane/gemcitabine and no prior irinotecan or Nal-IRI

Efficacy Endpoints

• Best overall response (complete response [CR] or partial response [PR]) and disease control rate (CR, PR or stable disease [SD])
• Progression-freesurvival (PFS) rate at 6 months
• Overall survival (OS)
• Reduction in KRAS allelic burden in liquid biopsies

What is Clinical Trial Success

• Achieve ≥26% overall response rate (ORR) - 9 out of 35 patients
• Achieve ≥36% progression free survival rate at 6 months - 13 out of 36 patients

2020 Corporation Presentation I 42

Corporate

Strong Patent Portfolio

Core Technology: 3 Issued Patents to 2030 in US, Europe and Asia, with anticipated extension to 2035

Compound (onvansertib): US 8614220

Salt forms of onvansertib: US 8648078

Combinations with anti-neoplastic compounds: US 8927530

PLK: Polo-like kinase; PSA: Prostate specific antigen

Evergreening: Combination Therapy

Exclusive license from MIT for 2 US issued patents with broad method claims for combination of PLK inhibitor + anti- androgen compounds to treat any cancer

US 9566280; US 10155006; Expiration 2035

Evergreening: Biomarkers

Method for assessing PLK1 target phosphorylation status for identifying patients to be treated with PLK1 inhibitors

PCT US1948044, Expiration 2039

Method for treating patient with a PLK inhibitor when there is a PSA rise

Provisional, Expiration 2040

2020 Corporation Presentation I 44

Cardiff Oncology At-A-Glance

Clinical-stage biotech company, developing onvansertib, an oral, highly-selectivePolo-like Kinase 1 (PLK1) inhibitor, to treat cancers with the greatest medical need for

new effective therapies

Exchange

Nasdaq: CRDF

Cash & Cash Equivalents (as of 10/31/20)

$131.8M

Q1 - Q3, 2020 Average Quarterly Cash Burn

$3.8M

Headquarters

San Diego, CA

2020 Corporation Presentation I 45

Investment Highlights

3rd Generation, 1st-in-class,

Oral PLK1 Inhibitor

Onvansertib overcomes the shortcomings of prior PLK inhibitors:

• Highly selective for PLK1
• Orally administered
• 24-hourhalf-life
• Flexible dose and schedule

Specifically targets a known mechanism of cell division that is required for tumor cell viability

Preliminary clinical data demonstrate the safety, tolerability and efficacy of onvansertib in combination with SOC across multiple indications

Strong Lead Program in KRAS-mutated mCRC

Supported by compelling preliminary clinical data from a Phase 1b/2 trial showing a ten-foldimprovement in ORR compared to SOC

Preclinical data support:

• MOA of synthetic lethality between KRAS mutant mCRC and PLK1 inhibition
• Synergy with irinotecan and 5-FU

First Indication: 2nd line treatment in patients who have failed 1st line treatment with FOLFOX with/without bevacizumab

FDA Fast Track Designation

Integrated Biomarker

Strategy

Circulating Tumor DNA: changes in KRAS mutational burden in blood are predictive of subsequent tumor shrinkage (mCRC)

Circulating Tumor Cells: changes are predictive of overcoming anti- androgen resistance (mCRPC)

Circulating Tumor DNA: changes are predictive of decreases in leukemic bone marrow cells (AML)

Diversified Pipeline Across

Numerous Cancers

Clinical data from ongoing trials support the use of onvansertib in combination regimens across numerous aggressive cancers:

• mCRC Phase 1b/2 trial
• mCRPC Phase 2 trial
• AML Phase 2 trial

Potential expansion opportunities:

• Chronic myelomonocytic leukemia
• Pancreatic cancer
• Triple negative breast cancer
• Lung cancer
• Ovarian cancer

PLK: Polo-like Kinase; SOC: Standard-of-care; ORR: Overall response rate; MOA: Mechanism of action; mCRC: metastatic colorectal cancer;

mCRPC: metastatic castration resistant prostate cancer; AML: Acute myeloid leukemia

2020 Corporation Presentation I 46

Thank You

for more information contact: [e-mail]