What changed in this filing

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Item 2. Management’s Discussion and Analysis

2023-11-02 compared with 2023-08-09 · 62 added, 59 removed, 118 unchanged (51% of the section changed)

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We are a clinical-stage biotechnology company leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers with the greatest unmet medical need.

Our goal is to target tumor vulnerabilities with treatment combinations of onvansertib, our oral and highly selective PLK1 inhibitor, and standard-of-care ("SoC") therapeutics.

We are focusing our clinical program in indications such as RAS-mutated metastatic colorectal cancer ("mCRC") and metastatic pancreatic ductal adenocarcinoma ("mPDAC"), as well as in investigator-initiated trials in triple negative breast cancer ("TNBC") and small cell lung cancer ("SCLC").

Our goal is to target tumor vulnerabilities with treatment combinations of onvansertib, our oral and highly selective PLK1 inhibitor, and standard-of-care therapeutics.

We are focusing our clinical program in indications such as RAS-mutated metastatic colorectal cancer ("mCRC") and metastatic pancreatic ductal adenocarcinoma ("mPDAC"), as well as in investigator-initiated trials in small cell lung cancer ("SCLC") and triple negative breast cancer ("TNBC").

Our clinical development programs incorporate tumor genomics and biomarker assays to refine assessment of patient response to treatment.

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There are five ongoing and planned clinical trials of onvansertib:

one trial (CRDF-004) in first line treatment in patients with RAS-mutated mCRC, one trial (TROV-054) in second line treatment in patients with KRAS-mutated Metastatic Colorectal Cancer ("mCRC"), one trial in second line treatment in patients with Metastatic Pancreatic Ductal Adenocarcinoma ("mPDAC"), and two investigator-initiated trials in patients with locally advanced or metastatic Triple Negative Breast Cancer ("TNBC") and relapsed Small Cell Lung Cancer ("SCLC").

one trial (CRDF-004) in first line treatment in patients with RAS-mutated mCRC, one trial (TROV-054) in second line treatment in patients with KRAS-mutated mCRC, one trial in second line treatment in patients with mPDAC, and two investigator-initiated trials in patients with relapsed extensive-stage SCLC and locally advanced or metastatic TNBC.

RAS-mutated mCRC Program:

CRDF-004 Clinical Trial in RAS-mutated mCRC

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Progression-free survival and duration of response will be secondary endpoints.

We expect to begin enrollment during the second half of 2023, with initial data anticipated in mid-2024.

The trial is expected to enroll approximately 90 patients.

We expect to begin enrollment during the fourth quarter of 2023, with interim data anticipated in mid-2024.

Pfizer Ignite is responsible for the clinical execution of the trial and it is expected to enroll approximately 90 evaluable patients.

For more information, please visit NCT06106308 at www.clinicialtrials.gov .

Contingent upon the results of CRDF-004, Cardiff Oncology plans to initiate CRDF-005, a Phase 3, randomized trial with registrational intent.

The FDA has agreed that a seamless trial with objective response rate (ORR) at an interim point is an acceptable endpoint to pursue accelerated approval, with progression-free survival and trend in overall survival being the endpoints for full approval.

Phase 1b/2 Clinical Trial in KRAS-mutated mCRC

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The primary objectives of this trial are to evaluate the Dose-Limiting Toxicities ("DLTs"), maximum tolerated dose ("MTD") and recommended Phase 2 dose ("RP2D") of onvansertib in combination with FOLFIRI and bevacizumab (Phase 1b) and to continue to assess the safety and preliminary efficacy of onvansertib in combination with FOLFIRI and bevacizumab patients with KRAS-mutated mCRC (Phase 2).

The scientific rationale for this clinical trial is based on the two key principles of synthetic lethality and synergy, with the objective of demonstrating a proof-of-concept of clinical benefit within this Phase 1b/2 trial.

Synthetic lethality refers to a critical vulnerability to tumor cell death by way of PLK1 inhibition within CRC tumor cells harboring KRAS mutations versus KRAS wild-type isogenic cells.

Synergy occurs when the combination of multiple drugs results in an unexpected greater activity than an expected additive effect of the individual drugs.

Onvansertib in combination with two DNA-damaging agents, irinotecan and 5-FU (two components of FOLFIRI), demonstrated synergy in colorectal cancer cell lines and both combinations have demonstrated significantly greater tumor growth inhibition than either drug alone in CRC in vivo models.

We believe this synergy occurs because PLK1 can promote the repair of DNA damage caused by chemotherapeutic agents and by inhibiting PLK1, onvansertib leaves damaged tumor cells unable to repair DNA damage from chemotherapy and then replicate.

For more information, please visit NCT03829410 at www.clinicialtrials.gov .

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• Median progression free survival ("mPFS") across all evaluable patients was 9.3 months (95% CI:

Historical control trials of different drug combinations, including the standard-of-care ("SOC") of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and ~4.5 – 6.7 months, respectively.

Historical control trials of different drug combinations, including the standard-of-care of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and ~4.5 – 6.7 months, respectively.

• A subgroup analysis of patients who were bevacizumab naïve when they entered 2 nd line therapy vs patients who had received prior bevacizumab in 1 st line therapy showed that patients who were bevacizumab naïve (n=15) had an ORR of 73% and mPFS of 15 months, which is well above historical controls.

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In reviewing the TROV-054 clinical data, we originally designed the ONSEMBLE trial (CRDF-003) as the next phase of our mCRC program.

Upon review of the clinical data from the bev naïve subgroup (those patients who did not receive bev in their 1 st line therapy), the preclinical data on the mechanism of action and the feedback from the FDA on our clinical development strategy, we made the decision to discontinue enrollment in the ONSEMBLE trial and to initiate CRDF-004.

Upon review of the clinical data from the bevacizumab naïve subgroup (those patients who did not receive bevacizumab in their 1 st line therapy), the preclinical data on the mechanism of action and the feedback from the FDA on our clinical development strategy, we made the decision to discontinue enrollment in the ONSEMBLE trial and to initiate the CRDF-004 clinical trial.

mDPAC Program:

Phase 2 Clinical Trial in mPDAC

CRDF-001 is a Phase 2 open-label multi-center clinical trial of onvansertib in combination with nanoliposomal irinotecan (Onivyde ® ), leucovorin, and fluorouracil for second line treatment of patients with mPDAC, which is being conducted at six clinical trial sites across the U.S.

CRDF-001 is a Phase 2 open-label multi-center clinical trial of onvansertib in combination with nanoliposomal irinotecan (Onivyde ® ), leucovorin, and fluorouracil for 2 nd line treatment of patients with mPDAC, which is being conducted at six clinical trial sites across the U.S.

– The Mayo Clinic Cancer Centers (Arizona, Minnesota, and Florida), Kansas University Medical Center, Inova Schar Cancer Institute, and the University of Nebraska Medical Center.

The first patient was dosed in June 2021.

The objective of this trial is to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide ® ), 5-FU and leucovorin as a second-line treatment in patients with mPDAC who have failed 1 st line gemcitabine-based therapy.

The trial is expected to enroll approximately 45 patients.

Enrollment for this trial closed in October 2023.

The objective of this trial is to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide ® ), 5-FU and leucovorin as a 2 nd line treatment in patients with mPDAC who have failed 1 st line gemcitabine-based therapy.

For more information, please visit NCT04752696 at www.clinicialtrials.gov .

Preliminary data presented on September 26, 2023 provided an update of the ongoing CRDF-001 Phase 2 open label clinical trial in mPDAC:

• Preliminary data from 5 evaluable patients showed 1 patient achieving an initial partial response ("PR") and 3 patients achieving stable disease ("SD");

• The 4 patients achieving SD or PR remain on study;

the fifth evaluable patient discontinued treatment due to disease progression and an additional 3 patients remain on study awaiting their first post-baseline scan;

• Additional data is expected in mid-2023.

Phase 1b/2 Investigator-Initiated Clinical Trial in TNBC

A single-arm, Phase 1b/2 trial of onvansertib in combination with paclitaxel in patients with unresectable locally advanced or metastatic TNBC is open for enrollment at Dana Farber Cancer Institute ("DFCI").

In Phase 1b, approximately 14-16 patients will be treated with different doses of onvansertib in combination with a fixed dose of paclitaxel to determine the maximum tolerated dose and RP2D of onvansertib.

In Phase 2, approximately 34 patients will be treated with the selected onvansertib RP2D in combination with paclitaxel.

The primary endpoint of Phase 2 of the trial is ORR, with PFS included as a secondary endpoint.

Preliminary data from the trial are expected in the fourth-quarter of 2023 or first-quarter of 2024.

For more information, please visit NCT05383196 at www.clinicialtrials.gov .

• Preliminary data from 21 patients evaluable for radiographic response showed 1 patient achieving a confirmed partial response (“PR”) and 3 patients achieving a partial response that are awaiting confirmatory scans;

• 19% objective response rate (“ORR”) achieved compared to historical control of 7.7% in 2nd line setting;

• 5.0 months median progression-free survival (“mPFS”) achieved compared to historical control of 3.1 months with standard of care (“SoC”);

mPDAC biomarker discovery trial

The investigator-initiated biomarker discovery trial is exploring the impact of onvansertib 10-day monotherapy on tumors in mPDAC patients, and is currently enrolling at the Oregon Health & Science University (OHSU) Knight Cancer Institute.

Two patients have been enrolled as of September 13, 2023.

Preliminary data were presented on September 26, 2023.

One patient demonstrated an 86% decrease in Ki67, a well-established biomarker of tumor proliferation, and a 28% decrease in CA 19-9, a clinically-used biomarker to monitor treatment response.

Other Clinical Programs:

Phase 2 Investigator-Initiated Clinical Trial in SCLC

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The primary endpoint of the trial is ORR, while key secondary endpoints include PFS and overall survival.

Preliminary data from the trial are expected in mid-2023.

For more information, please visit NCT05450965 at www.clinicialtrials.gov .

Recent Updates

Pfizer Ignite to Conduct CRDF-004 Clinical Trial

Pfizer Ignite will conduct the clinical activities of our new CRDF-004 trial in 1st line RAS-mutated mCRC, which expands the relationship established in November 2021 when Pfizer made an investment in Cardiff Oncology through its Pfizer Breakthrough Growth Initiative.

Pfizer VP and Development head Adam Schayowitz sits on the Cardiff Oncology Scientific Advisory Board.

An examination of the safety data from the first six patients by the institutional review board confirmed the trial can continue to enroll as planned.

Preliminary efficacy data for seven patients presented on September 26, 2023, showed 1 confirmed partial response (“PR”), three stable disease (“SD”) and three progressive disease (“PD”).

The disease control rate, including PR and SD, is 57% (4 of 7 patients).

Phase 1b/2 Investigator-Initiated Clinical Trial in TNBC

In Phase 2, approximately 34 patients will be treated with the selected onvansertib RP2D in combination with paclitaxel.

The primary endpoint of Phase 2 of the trial is ORR, with PFS included as a secondary endpoint.

For more information, please visit NCT05383196 at www.clinicialtrials.gov .

Critical Accounting Policies

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RESULTS OF OPERATIONS

Three Months Ended June 30, 2023 and 2022

Total revenues were $108,000 for the three months ended June 30, 2023, as compared to $91,000 for the prior period.

Three Months Ended September 30, 2023 and 2022

Total revenues were $141,000 for the three months ended September 30, 2023, as compared to $93,000 for the prior period.

Revenues are from our sales-based or usage-based royalties on other intellectual property licenses, unrelated to onvansertib.

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Research and development expenses consisted of the following:

Three Months Ended June 30,

Three Months Ended September 30,

(in thousands) 2023 2022 Increase (Decrease)

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Total research and development $ 8,022 $ 6,009 $ 2,013

Research and development expenses increased by $0.6 million for the three months ended June 30, 2023, compared to the same period in 2022.

The overall increase in expenses was primarily related to salaries and staff costs from additional hires in senior management and our clinical operations team (research and development average headcount grew by 35% over the comparative period).

The increase in facilities and other is primarily due to increased allocation of facilities cost resulting from headcount growth compared to the prior period.

The decrease in clinical trials, outside services, and lab supplies was primarily related to costs incurred in the prior period related to CMC and clinical pharmacology for studies to support the development of our lead drug candidate, onvansertib.

Research and development expenses increased by $2.0 million for the three months ended September 30, 2023, compared to the same period in 2022.

The overall increase in expenses was primarily due to costs associated with clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib.

The increase in salaries and staff costs from additional hires in senior management and our clinical operations team (research and development average headcount grew by 50% over the comparative period).

Selling, General and Administrative Expenses

Selling, general and administrative expenses consisted of the following:

Three Months Ended June 30,

Three Months Ended September 30,

(in thousands) 2023 2022 Increase (Decrease)

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Total selling, general and administrative $ 2,939 $ 3,077 $ (138)

Selling, general and administrative expenses increased by $1.2 million for the three months ended June 30, 2023, compared to the same period in 2022.

Salaries and staff costs increased due to an employee severance agreement.

The increase in outside services and professional fees was due to additional contract review legal fees, public relations and external accounting fees.

Selling, general and administrative expenses decreased by $0.1 million for the three months ended September 30, 2023, compared to the same period in 2022.

Salary and staff costs and stock-based compensation decreased due to lower headcount.

Facilities and other costs were lower as a result of a reduction of insurance costs compared to the prior period.

The increase in outside services and professional fees was due mainly to additional legal fees for contract reviews.

Interest Income, Net

Interest income, net was $1.1 million for the three months ended June 30, 2023 as compared to $0.3 million for the same period of 2022.

The increase in interest income was primarily due to higher interest rates on our short-term investments portfolio for the three months ended June 30, 2023 as compared to the same period of 2022.

Six Months Ended June 30, 2023 and 2022

Total revenues were $191,000 for the six months ended June 30, 2023, as compared to $165,000 for the same period in 2022.

Interest income, net was $1.1 million for the three months ended September 30, 2023 as compared to $0.5 million for the same period of 2022.

The increase in interest income was primarily due to higher interest rates on our short-term investments portfolio for the three months ended September 30, 2023 as compared to the same period of 2022.

Nine Months Ended September 30, 2023 and 2022

Total revenues were $332,000 for the nine months ended September 30, 2023, as compared to $258,000 for the same period in 2022.

Revenues are from our sales-based or usage-based royalties on other intellectual property licenses, unrelated to onvansertib.

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Research and development expenses consisted of the following:

Six Months Ended June 30,

Nine Months Ended September 30,

(in thousands) 2023 2022 Increase (Decrease)

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Total research and development $ 25,094 $ 20,665 $ 4,429

Research and development expenses increased by $2.4 million for the six months ended June 30, 2023, compared to the same period in 2022.

Research and development expenses increased by $4.4 million for the nine months ended September 30, 2023, compared to the same period in 2022.

The overall increase in expenses was primarily due to costs associated with clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib.

Salaries and staff costs increased primarily from additional hires in senior management and our clinical operations team (research and development average headcount grew by 37% over the comparative period).

The increase in facilities and other is primarily due to increased allocation of facilities cost resulting from headcount growth compared to the prior period.

The increase in facilities and other costs is primarily due to increased allocation of facilities cost resulting from headcount growth compared to the prior period.

Selling, General and Administrative Expenses

Selling, general and administrative expenses consisted of the following:

Six Months Ended June 30,

Nine Months Ended September 30,

(in thousands) 2023 2022 Increase (Decrease)

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Total selling, general and administrative $ 10,318 $ 10,103 $ 215

Selling, general and administrative expenses increased by $0.4 million for the six months ended June 30, 2023, compared to the same period in 2022.

Selling, general and administrative expenses increased by $0.2 million for the nine months ended September 30, 2023, compared to the same period in 2022.

Salaries and staff costs increased due to an employee severance agreement.

The decrease in facilities and other costs was primarily due to reduced insurance costs compared to the prior period.

Interest Income, Net

Interest income, net was $2.0 million for the six months ended June 30, 2023 as compared to $0.4 million for the same period of 2022.

The increase in interest income was primarily due to higher interest rates on our short-term investments portfolio for the six months ended June 30, 2023 as compared to the same period of 2022.

Interest income, net was $3.1 million for the nine months ended September 30, 2023 as compared to $0.8 million for the same period of 2022.

The increase in interest income was primarily due to higher interest rates on our short-term investments portfolio for the nine months ended September 30, 2023 as compared to the same period of 2022.

LIQUIDITY AND CAPITAL RESOURCES

Net cash used in operating activities for the six months ended June 30, 2023, was $15.8 million, compared to $16.9 million for the six months ended June 30, 2022.

Our use of cash was primarily a result of the net loss of $22.4 million for the six months ended June 30, 2023, adjusted for non-cash items related to stock-based compensation of $2.6 million.

Net cash used in operating activities for the nine months ended September 30, 2023, was $23.7 million, compared to $24.4 million for the nine months ended September 30, 2022.

Our use of cash was primarily a result of the net loss of $32.1 million for the nine months ended September 30, 2023, adjusted for non-cash items related to stock-based compensation of $3.6 million.

The net change in our operating assets and liabilities decreased cash used in operations by $5.2 million.

At our current and anticipated level of operating loss, we expect to continue to incur an operating cash outflow for the next several years.

Net cash provided by investing activities was $18.8 million primarily related to sales and maturities in excess of purchases of marketable securities for the six months ended June 30, 2023, compared to net cash provided by investing activities of $26.0 million primarily related to sales and maturities in excess of purchases of marketable securities during the same period in 2022.

Net cash provided in financing activities was $0 for the six months ended June 30, 2023, and 2022.

As of June 30, 2023, and December 31, 2022, we had working capital of $83.6 million and $103.5 million, respectively.

Net cash provided by investing activities was $22.6 million primarily related to sales and maturities in excess of purchases of marketable securities for the nine months ended September 30, 2023, compared to net cash provided by investing activities of $31.1 million primarily related to sales and maturities in excess of purchases of marketable securities during the same period in 2022.

Net cash provided in financing activities was $0 for the nine months ended September 30, 2023, compared to net cash provided by financing activities of $0.1 million during the same period of 2022.

As of September 30, 2023, and December 31, 2022, we had working capital of $74.9 million and $103.5 million, respectively.

We have incurred net losses since our inception and have negative operating cash flows.

As of June 30, 2023, we had $89.4 million in cash, cash equivalents and short-term investments and we believe we have sufficient cash to meet our funding requirements for at least the next 12 months following the issuance date of this Quarterly Report on Form 10-Q.

As of September 30, 2023, we had $81.4 million in cash, cash equivalents and short-term investments and we believe we have sufficient cash to meet our funding requirements for at least the next 12 months following the issuance date of this Quarterly Report on Form 10-Q.

Based on our current projections we expect that our capital resources are sufficient to fund our operations into 2025.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis