On May 6, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing onvansertib to treat cancers with the greatest medical needs for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer and castrate-resistant prostate cancer, reported recent company highlights and financial results for the first quarter ended March 31, 2021 (Press release, Cardiff Oncology, MAY 6, 2021, View Source [SID1234579336]). The Company is issuing this press release in lieu of conducting a conference call.

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"We are off to a strong start in 2021 thanks in large part to our successful financing late last year, which has allowed us to advance our clinical development programs, more fully leverage onvansertib combination trials across multiple cancer indications, and work towards strengthening company leadership," said Dr. Mark Erlander, chief executive officer of Cardiff Oncology. "As presented at ASCO (Free ASCO Whitepaper)-GI in January and our KOL Event in early April, our KRAS-mutated metastatic colorectal cancer (mCRC) trial continues to generate consistent and encouraging data, with a robust overall response rate and median progression free survival that compare favorably to historical controls. These data also provide a strong scientific rationale for our Phase 2 trial in pancreatic ductal adenocarcinoma (PDAC), an indication where approximately 95% of patients have a KRAS mutation. We recently activated our first sites for this trial, which, similar to our mCRC trial, will treat patients with onvansertib in combination with irinotecan and 5-FU."

Dr. Erlander continued, "The progress in our KRAS-mutated cancer programs is complemented by promising data from our Phase 2 trial in metastatic castrate-resistant prostate cancer (mCRPC), which continues to demonstrate durable disease control in patients showing initial abiraterone resistance and highlights onvansertib’s ability to disrupt or inhibit additional tumor-promoting pathways. In parallel, in vitro studies in mCRPC indicate that onvansertib and abiraterone can synergistically interact by upregulating a mitosis related gene signature and disrupting mitotic spindle orientation. We are currently testing this prospectively in our ongoing trial to assess whether the presence of this signature in the tumor can predict which patients are most likely to respond to onvansertib-abiraterone combination therapy. We look forward to the continued progression of this trial as well as our other clinical programs, which together are expected to drive increased value throughout 2021."

Program highlights for the quarter ended March 31, 2021, along with recent developments, include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced updated data from the Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab that continues to demonstrate robust response to treatment and progression-free survival in KRAS-mutated mCRC

Updated data from Cardiff Oncology’s Phase 1b/2 mCRC trial were presented in conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) in January and as part of a separate Key Opinion Leader webinar in April. Results from the trial continue to show robust patient response and progression-free survival when onvansertib is combined with standard-of-care therapy in second line KRAS-mutated mCRC. Data highlights from the Phase 1b trial, as of April 4, 2021, include:

7 of 18 (39%) evaluable patients achieved a partial response (PR); 4 patients had a confirmed PR with 1 patient going on to curative surgery; 1 patient with a non-confirmed PR went off study following PR prior to confirmatory scan due to a treatment-unrelated adverse event; 2 patients with non-confirmed PRs await confirmatory scans and results
Evaluable patients have a median progression free survival (mPFS) of 9.4 months (95% confidence interval: 7.85 months – not reached), more than double the historical 4.5-month mPFS from analysis of 23 randomized trials in second-line metastatic colorectal cancer (data from ~10,800 patients)¹
7 patients remain on treatment
Clinical responses were observed across different KRAS mutations, including the 3 most common in colorectal cancer (G12D, G12V, G13D)
The greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle of treatment were observed in patients achieving a PR
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no major or unexpected toxicities attributed to onvansertib
Enrollment of patients in the Phase 1b segment of the trial concluded in December 2020 and the first patient in the Phase 2 segment of the trial had their first treatment in February 2021. Phase 2 is rapidly accruing the approximately 26 patients needed to complete the study across 7 trial sites: USC Norris Comprehensive Cancer Center, Mayo Clinic Cancer Centers (Arizona, Rochester and Jacksonville), Kansas University Medical Center, CARTI Cancer Center and Inova Schar Cancer Institute.

Presented findings from the Expanded Access Program (EAP) for onvansertib in KRAS-mutated mCRC highlighting the clinical benefit of onvansertib in heavily pretreated patients

Findings from Cardiff Oncology’s EAP were presented at ASCO (Free ASCO Whitepaper)-GI in January and at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 in April. The EAP has enrolled participants who failed or progressed on multiple lines of standard-of-care treatment and uses the same combination regimen (onvansertib 15 mg/m2 + FOLFIRI/bevacizumab) and dosing schedule as the ongoing Phase 1b/2 mCRC clinical trial. In the most recent update at the AACR (Free AACR Whitepaper) Annual Meeting, the Company presented findings from 20 evaluable participants who were heavily pre-treated (median of 3 prior lines of treatment). Highlights from the AACR (Free AACR Whitepaper) presentation included:

15 of 20 (75%) evaluable participants received an irinotecan-based regimen as their last therapy prior to enrolling in the EAP.
13 of 20 (65%) evaluable participants were progressing prior to enrolling in the EAP
Median progression free survival (mPFS) was 5.6 months (95% confidence interval: 2.7 months – not reached), which is significantly greater than historical controls (2-3 months)2
62.5% of participants had a greater than 50% decrease in KRAS MAF after one cycle of treatment and continue to show a durable response and have not reached mPFS
11 of 20 of evaluable participants remain on treatment
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no serious adverse events (SAEs) reported
Hosted a Key Opinion Leader (KOL) webinar highlighting the findings from the onvansertib Phase 1b/2 trial and EAP

The call featured KOLs Daniel H. Ahn, D.O., M.S. (Mayo Clinic Arizona), and Manish R. Sharma, M.D. (START Midwest). In addition to highlighting the latest data and findings from the onvansertib Phase 1b/2 mCRC trial and EAP, the call also included an overview of the current treatment landscape in KRAS-mutated mCRC and a discussion of the response rates and progression free survival historically achieved with the current second-line standard of care. You may access a replay of the event by clicking here.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Announced updated Phase 2 data showing a two-fold increase in efficacy with an optimized onvansertib dosing schedule

Updated data from a Phase 2 trial evaluating the all-oral combination of onvansertib, abiraterone and prednisone in patients showing initial abiraterone resistance were featured in a virtual oral poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO-GU). These data showed that increasing the number of days of treatment with onvansertib from 5 to 14 in a 21-day cycle was associated with a greater than two-fold increase (29% to 63%) in disease control rate (DCR) at 12 weeks, the trial’s primary efficacy endpoint. Across all cohorts, the DCR at 12 weeks is 35% (13/37), indicating the trial is on track to meet the stated criteria for success on the primary efficacy endpoint (30% DCR at 12 weeks). Additional highlights from the ASCO (Free ASCO Whitepaper)-GU presentation included:

The optimized dosing schedule of cohort C shows a greater than two-fold improvement in disease control rate compared to cohorts A and B, with 63% (5/8) of cohort C patients achieving the primary efficacy endpoint compared to 29% (5/17) and 25% (3/12) of cohort A and B patients, respectively
75% (6/8) of evaluable patients in cohort C had radiographic stable disease (SD) at 12 weeks, compared to 53% (9/17) in cohort A, 42% (5/12) in cohort B and 54% (20/37) across all cohorts
All cohort C patients achieving the primary efficacy endpoint remain on treatment
Data show that the combination of onvansertib and abiraterone is well tolerated across all dosing cohorts.
Additional information on the trial and dosing cohorts can be found here.

Identified an androgen-independent mechanism of synergy between onvansertib and abiraterone in mCRPC

Collaborative studies with the Massachusetts Institute of Technology featured in a virtual oral poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2021 suggest that the androgen receptor signaling inhibitor abiraterone sensitizes certain prostate cancer cells to onvansertib via the induction of a mitosis related gene signature and disruption of mitotic spindle orientation. These results are consistent with previous findings showing that onvansertib and abiraterone synergize in an androgen receptor-independent manner in vitro and in vivo. Data from the studies also suggest that the identified mitosis related gene signature may be predictive of patient response to onvansertib-abiraterone combination therapy, a hypothesis that is being further assessed in the ongoing Phase 2 mCRPC trial.

Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Program:

Opened enrollment for a Phase 2 trial of onvansertib in metastatic PDAC

Cardiff Oncology recently activated the first clinical sites for its Phase 2 clinical trial of onvansertib in metastatic PDAC, which is now open for enrollment. The trial is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onivyde), leucovorin and fluorouracil (5-FU) as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. Onvansertib’s potential in PDAC, where ~95% of patients have a KRAS mutation, is supported by the promising clinical data seen in KRAS-mutated mCRC patients treated with the combination of onvansertib, irinotecan and 5-FU (FOLFIRI).

Sale of Common Stock to Institutional Investor:

On May 5, 2021, the Company agreed to sell 2.0 million shares of its Common Stock to a healthcare institutional investor for gross proceeds of $20.0 million under the Sales Agreement with Jeffries LLC.

First Quarter 2021 Financial Results:

As of March 31, 2021, Cardiff Oncology had approximately $125.6 million in cash, cash equivalents and short-term investments.

Total operating expenses were approximately $5.5 million for the three months ended March 31, 2021, an increase of $1.3 million from $4.2 million for the same period in 2020. The increase in operating expenses is attributed to advancing onvansertib drug development activities, additional clinical studies and increased outside services for legal fees mainly related to the expansion of our patent portfolio and recruiting fees.

Net cash used in operating activities in the first quarter of 2021 was $5.9 million, an increase of $2.5 million from $3.4 million for the same period in 2020. The increase is attributed to expanding and advancing drug development and clinical program activities, and net changes in assets and liabilities.

Research and development expenses increased by approximately $0.6 million to $3.3 million for the three months ended March 31, 2021, from $2.7 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs.

Selling, general and administrative expenses increased by approximately $0.7 million to $2.2 million for the three months ended March 31, 2021, from $1.5 million for the same period in 2020. The increase is primarily due to increased outside services for legal fees mainly related to the expansion of our patent portfolio and recruiting fees.