On February 25, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer, castrate-resistant prostate cancer and leukemias, reported recent company highlights and financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Cardiff Oncology, FEB 25, 2021, View Source [SID1234575717]).

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"Over the last several months we achieved key clinical milestones, which provided the momentum for our successful raise of over $100 million. Together, these events have enabled us to accelerate the execution of our clinical programs and expand our pipeline to other relevant cancer indications," said Dr. Mark Erlander, chief executive officer of Cardiff Oncology. "Data from our lead KRAS-mutated metastatic colorectal cancer (mCRC) program show promising and durable efficacy, highlighting the potential of onvansertib in combination with standard-of-care FOLFIRI (irinotecan and 5-FU)/bevacizumab to address the need for a new second-line treatment option. Importantly, we completed enrollment in the Phase 1b portion of this trial in December of 2020 and initiated patient accrual in the Phase 2 segment in January of this year. Based on the mCRC trial results, we are leveraging the known synergy of onvansertib with irinotecan and 5-FU by evaluating this combination (nanoliposoamal irinotecan and 5-FU) in pancreatic ductal adenocarcinoma (PDAC). Approximately 95% of PDAC patients have a KRAS mutation and current second-line treatment for this indication conveys only a 7.7% response rate and 6-month median overall survival benefit. We plan to initiate a Phase 2 trial in this indication in the first half of the year following the receipt of our "study may proceed" notification from the FDA last month. Our goal is to further demonstrate the broad applicability of onvansertib across KRAS-mutated cancers and to address an indication with a significant unmet need for new treatment options."

Dr. Erlander continued, "Onvansertib’s broad applicability extends beyond targeting KRAS-mutated cancers, as shown by the exciting progress of our metastatic castrate-resistant prostate cancer (mCRPC) trial. The addition of onvansertib to daily abiraterone treatment in patients showing initial resistance to abiraterone has resulted in durable disease control. Notably, the most recent data presented at ASCO (Free ASCO Whitepaper)-GU showed a significant increase in disease control rate in patients receiving onvansertib for more days within a treatment cycle. Looking ahead, the progress we’ve made across our clinical programs leaves us poised to achieve a steady cadence of catalysts throughout 2021 and beyond as we continue to advance onvansertib’s development."

Program highlights for the quarter ended December 31, 2020 include:

Corporate Milestones:

Raised gross proceeds of approximately $100 million in an offering of common stock

Cardiff Oncology substantially strengthened its balance sheet in the fourth quarter, closing an underwritten public offering of 6,500,000 shares of its common stock at a public offering price of $13.50 per share, before deducting underwriter discounts and commissions and estimated offering expenses. The underwriters also exercised an option to purchase an additional 975,000 shares at the public offering price (less the underwriting discounts and commissions). The Company intends to use the net proceeds from this offering for clinical development of onvansertib, working capital and for other general corporate purposes.

Appointed Dr. Rodney Markin as Chairman of the Board

Prior to being appointed Chairman, Dr. Markin previously served as a Director on Cardiff’s Board from February 2014 to December 2020. He has extensive medical expertise and experience in institutional healthcare, and is currently the Vice President for Network Development, Nebraska Medicine and Associate Vice Chancellor for Business and Executive Director of the UNeTech Institute at the University of Nebraska Medical Center. In addition to currently holding several other distinguished positions in academia, Dr. Markin also has served on the boards of Perceptimed Inc. since 2014, MikroScan Technologies Inc. since 2015, Afaxys Inc. since 2017 and Paradigm Diagnostics Inc. since 2018.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Identified a biomarker associated with onvansertib-abiraterone synergy that is enriched in mCRPC patients with the clinically defined basal molecular tumor subtype

Collaborative studies with the Massachusetts Institute of Technology and Decipher Biosciences identified a gene signature (biomarker) related to cell division pathways that can be used to predict which cancer cells will show a synergistic anti-tumor response to treatment with onvansertib in combination with abiraterone. This gene signature is correlated with the clinically defined basal molecular subtype of mCRPC, suggesting that patients with this tumor subtype may be more likely to respond to onvansertib-abiraterone combination therapy. These studies were featured in an electronic poster at the 27th Annual Prostate Cancer Foundation Scientific Retreat.

Acute Myeloid Leukemia (AML) Program:

Presented data at ASH (Free ASH Whitepaper) demonstrating the safety and anti-leukemic activity of onvansertib in relapsed/refractory AML

Updated data from a Phase 1b/2 clinical trial evaluating onvansertib in combination with decitabine in relapsed/refractory AML patients were featured in a virtual oral poster presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data demonstrated the safety, tolerability and anti-leukemic activity of the onvansertib-decitabine combination and showed an over-representation of splicing factor mutations in patients achieving a complete response. Additional highlights from the presentation included:

9 of 45 (20%) evaluated patients achieved a complete remission with or without hematologic count recovery (CR/CRi – 5 in Phase 1b and 4 in Phase 2)
55% of responders had a mutation in a splicing factor
2 patients proceeded to transplant following CR and 3 patients had ongoing responses as of the ASH (Free ASH Whitepaper) data cutoff
4 patients have achieved a durable response (≥9 months) – as of data cut-off date
Decreases in mutant circulating tumor DNA (ctDNA) within the first treatment cycle appeared to be highly correlated with clinical response; 7 of 7 (100%) patients with CR/CRi showed a decrease in mutant ctDNA after one cycle of treatment, while only 2 of 15 (13%) non-responders showed a similar decrease
Data demonstrated that onvansertib in combination with decitabine is a safe and well-tolerated treatment regimen
Highlights for the period subsequent to the quarter end include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced updated data from its Phase 1b/2 trial evaluating onvansertib plus FOLFIRI (irinotecan and 5-FU)/bevacizumab in second line KRAS-mutated mCRC patients and initial findings from its Expanded Access Program (EAP)

In conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), Cardiff Oncology announced updated Phase 1b data demonstrating the clinical benefit of onvansertib in KRAS-mutated mCRC, as well as initial findings from its EAP. Data highlights from the Phase 1b trial, as of January 6, 2021, include:

12 of 14 (86%) evaluable patients achieved a clinical benefit (SD – stable disease plus PR – partial response)
5 of 14 (36%) evaluable patients achieved a PR; 4 patients had a confirmed PR; 1 patient went on to have curative surgery; 1 patient with a non-confirmed PR went off study following PR due to a treatment-unrelated AE
3 patients with SD remain on treatment, including 2 who have yet to have their 16-week (second) scan; time to achieving a PR ranges from 2 to 6 months in trial participants on treatment
Clinical responses were observed across different KRAS variants, including the 3 most common in colorectal cancer
Patients achieving a PR or SD showed the greatest decrease in plasma mutant KRAS after one cycle of therapy
The combination of onvansertib and FOLFIRI/bevacizumab was well tolerated
Enrollment of patients in the Phase 1b segment of the trial is complete and the recommended Phase 2 dose of onvansertib has been confirmed at 15 mg/m2. The Phase 2 segment of the trial is open to full enrollment of approximately 26 patients across 6 trial sites: USC Norris Comprehensive Cancer Center, Mayo Clinic Cancer Centers (Arizona, Rochester, Jacksonville), Kansas University Medical Center and CARTI Cancer Center.

In the EAP, Cardiff Oncology announced that 6 of the initial 9 patients treated showed tumor shrinkage and remained on treatment with durable responses lasting an average of 6 months. Notably, 5 different KRAS mutation subtypes were represented amongst these patients and most patients had received prior treatment with FOLFIRI and progressed before enrolling in the EAP.

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 its primary efficacy endpoint (30% DCR at 12 weeks). Additional highlights from the 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
o 63% (5/8) of cohort C patients achieved 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 the three different dosing schedules of cohorts A-C:
Cohort A: 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort B: 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort C: 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Program:

Received "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) to begin a Phase 2 trial of onvansertib in metastatic PDAC

The Phase 2 clinical trial of onvansertib in metastatic PDAC is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide), 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 the KRAS-mutated mCRC trial evaluating onvansertib in combination with irinotecan and 5-FU (FOLFIRI). Initiation of the Phase 2 trial is expected in the first half of 2021.

Fourth Quarter Financial Results:

As of December 31, 2020, Cardiff Oncology had approximately $131 million in cash and cash equivalents.

Net cash used in operating activities in the fourth quarter of 2020 was $5.1 million, an increase of $1.8 million from $3.3 million for the same period in 2019. The increase is attributed mainly to outside services and professional fees, facilities and other and changes in operating assets and liabilities.

Research and development expenses increased by approximately $0.3 million to $3.2 million for the three months ended December 31, 2020, from $2.9 million for the same period in 2019. The increase in research and development expenses was primarily due to the increased outside service costs and clinical studies for advancing the development of our drug candidate, onvansertib. We expect increases in research and development costs to continue as we advance the onvansertib clinical development programs.

Selling, general and administrative expenses increased by approximately $1.9 million to $3.4 million for the three months ended December 31, 2020, from $1.5 million for the same period in 2019. The increase is primarily due to a one time increase in stock compensation expense, and outside services and professional fees.