On May 5, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported recent company highlights and financial results for the first quarter ended March 31, 2022 (Press release, Cardiff Oncology, MAY 5, 2022, View Source [SID1234613721]).

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"With a strong balance sheet and clinical data highlighting onvansertib’s potential to improve patient outcomes by combining synergistically with the standard-of-care, we believe we are well positioned for success," said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "Phase 1b/2 data from our lead KRAS-mutated metastatic colorectal cancer (mCRC) program show clear improvements in treatment response and durability compared to historical controls. These results also clinically demonstrate onvansertib’s KRAS-agnostic mechanism of action, setting it apart from competing agents that target only the G12C variant."

Dr. Erlander added, "We are also highly encouraged by recent data from our Phase 2 prostate cancer trial showing clinically meaningful disease control rates in patients who showed signs of progression on prior therapy, and preclinical studies that showed onvansertib-PARP inhibitor combination therapy leading to statistically significant survival benefits in patient-derived xenograft models of PARP-inhibitor-resistant ovarian cancer. These results further highlight how onvansertib’s ability to inhibit PLK1 positions it to target tumor vulnerabilities and overcome treatment resistance across a spectrum of indications. We look forward to building on these results as we move towards the second half of the year."

Program highlights for the quarter ended March 31, 2022, and recent business updates include:

KRAS-mutated mCRC Program:

Reported new Phase 1b/2 data showing treatment with onvansertib plus FOLFIRI/bevacizumab leading to an objective response rate (ORR) and median progression-free survival (mPFS) that substantially exceed those recorded in historical control trials

The data were announced on a webcast and conference call hosted by Cardiff Oncology, and a subset were presented by Heinz-Josef Lenz, M.D., FACP, principal investigator, USC Norris Comprehensive Cancer Center, in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). Highlights from the webcast and conference call include:

Efficacy data in evaluable patients:

Among patients treated per protocol with onvansertib at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI/bevacizumab:
34% (12 of 35) achieved an initial complete response (CR) or partial response (PR)
29% (10 of 35) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
Historical control trials evaluating different drug combinations, including the standard-of-care of FOLFIRI with bevacizumab, in similar patient populations have shown ORRs of 5-13%1-4
Patients evaluable for response treated at onvansertib dose levels 12 mg/m2, 15 mg/m2, and 18 mg/m2
35% (17 of 48) achieved an initial CR or PR
27% (13 of 48) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
mPFS, biomarker, and safety data:

mPFS not yet reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in historical control trials1-4
Complete or partial responses were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)
Onvansertib in combination with FOLFIRI/bevacizumab has been well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Metastatic Castration-resistant Prostate Cancer (mCRPC) Program:

Announced updated clinical and new biomarker data from Phase 2 trial evaluating onvansertib in combination with abiraterone/prednisone in mCRPC patients showing initial abiraterone resistance

Results from the trial, which were presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, showed clinically meaningful disease control rates that rose with increasing onvansertib dose density. Additional highlights from the announcement include:

75% (15 of 20) evaluable patients in Arm C, which represents the trial’s most dose dense treatment schedule, showed disease control by radiographic stable disease (SD/PR) at 12-weeks, compared to 9 of 17 (53%) and 11 of 19 (58%) in the less dose-dense Arms A and B, respectively
Treatment response (SD/PR) was positively associated with mutations in PTEN and MTOR, key genes in the PI3K signaling pathway
Gene signatures correlating with treatment response included those corresponding to the ERG+ and Notch pathways, which are involved in cell-invasion, epithelial-mesenchymal transition, and metastasis
Genes related to mitochondrial and immune functions were downregulated in patients achieving SD or a PR compared to those showing progressive disease
Onvansertib in combination with abiraterone/prednisone has been well tolerated in the trial
Each arm in the trial has evaluated a different dosing schedule of onvansertib alongside abiraterone and prednisone administered throughout the respective treatment cycle. Arm A evaluated 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, Arm B evaluated 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, and Arm C is evaluating 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles.

Preclinical Highlights:

Reported new preclinical data that show onvansertib combining with a PARP inhibitor to overcome PARP inhibitor (PARPi) resistance in BRCA1-mutant and wild-type patient-derived xenograft ovarian cancer models

Preclinical studies featured in a poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting evaluated onvansertib in combination with the PARPi olaparib in three olaparib-resistant patient-derived xenograft (PDX) ovarian cancer models. Two of the three PDX models studied were cisplatin-sensitive with a mutated BRCA1 gene, while the third was cisplatin-resistant with wild type BRCA1. Results showed that treatment with onvansertib plus olaparib led to a statistically significant survival benefit compared to treatment with either agent alone in each of the three evaluated PDX models. The combination regimen was also shown to be well tolerated in mice.

First Quarter 2022 Financial Results:

Liquidity and cash burn

As of March 31, 2022, Cardiff Oncology had approximately $129.4 million in cash, cash equivalents, and short-term investments.

Net cash used in operating activities for the first quarter of 2022 was approximately $10.2 million, an increase of approximately $4.3 million from $5.9 million for the same period in 2021.

The overall increase in research and development expenses was primarily due to costs associated with an increase in outside service costs related to chemistry, manufacturing, and controls ("CMC") and pharmacology for the development of our lead drug candidate, onvansertib. Salaries and staff costs increased due to a higher headcount in the current period, as compared to the prior period. The increase in stock-based compensation is due to additional stock option grants to employees granted subsequent to the prior period.

The overall increase in selling, general and administrative expense was primarily due to costs associated with outside services and stock-based compensation. The increase in outside services is related to strategic valuation consulting related to our lead drug candidate, onvansertib. The increase in stock-based compensation is due to additional stock option grants to employees and directors granted subsequent to the prior period.