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Item 1. Business

2021-02-25 compared with 2020-02-27 · 88 added, 96 removed, 271 unchanged (40% of the section changed)

We are a clinical-stage, oncology therapeutics company, taking a precision medicine approach to target cancers that are in need of new treatment options including KRAS-mutated metastatic colorectal cancer (“mCRC”), metastatic castrate-resistant prostate cancer (“mCRPC”) and acute myeloid leukemia (“AML”).

We are a clinical-stage, biotechnology company, developing new treatment options for cancer patients in indications with the greatest medical need, including KRAS-mutated metastatic colorectal cancer (“mCRC”), pancreatic cancer, metastatic castrate-resistant prostate cancer (“mCRPC”) and leukemias.

By integrating biomarkers into our clinical development programs, we will be able to identify patients who are most likely to respond to treatment across a number of cancer types and associated indications.

Our drug candidate, onvansertib (formerly known as PCM-075), is a first-in-class, third-generation, oral and highly-selective Polo-like Kinase 1 (“PLK1”) adenosine triphosphate (“ATP”) competitive inhibitor.

Our drug candidate, onvansertib, is a first-in-class, third-generation, oral and highly selective Polo-like Kinase 1 (“PLK1”) adenosine triphosphate (“ATP”) competitive inhibitor.

PLK1 is essential for precisely regulating the cell division and maintaining genome stability in mitosis (cell division), spindle assembly, and DNA damage response.

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Data has shown that blocking the expression of PLK1 by kinase inhibitors can effectively inhibit proliferation and induce apoptosis (death) of tumor cells.

On March 15, 2017, we announced the licensing of onvansertib, a PLK1 inhibitor, from Nerviano Medical Sciences S.r.l.

(“Nerviano”), the largest oncology research and development company in Italy and a leader in protein kinase drug development (Polo-like Kinase Inhibitors).

On March 15, 2017, we announced the licensing of onvansertib from Nerviano Medical Sciences S.r.l.

(“Nerviano”), the largest company in Italy committed to innovation and research and development in oncology and a leader in protein kinase drug development (Polo-like Kinase Inhibitors).

We believe onvansertib is the only PLK1 selective ATP competitive inhibitor administered orally with apparent antitumor activity in different preclinical models currently in clinical development.

The Polo-like Kinase family consists of 5 members (PLK1-PLK5) and they are involved in multiple functions in cell division, including the regulation of centrosome maturation, checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many others.

PLK1 plays a crucial role in the regulation of mitotic checkpoints.

The over-expression of PLK1 can lead to immature cell division with aneuploidy, a hallmark of cancer.

PLK1 is over-expressed in a wide variety of hematologic and solid tumor malignancies including colorectal, prostate, lung, breast, as well as leukemias and lymphomas.

In addition, several studies have shown that over-expression of PKL1 correlates with poor prognosis.

Onvansertib has been tested in-vivo in different xenograft and transgenic models at times suggesting tumor growth inhibition or tumor regression when used in combination with other therapies.

Onvansertib has been tested for antiproliferative activity on a panel of 148 tumor cell lines and appeared highly active with an IC 50 (a measure concentration for 50% target inhibition) below 100 nM in 75 cell lines and IC 50 values below 1 uM in 133 out of 148 cell lines.

PLK1 is the most well-characterized member of the family of serine/threonine protein kinases and strongly promotes the progression of cells through mitosis.

PLK1 performs several important functions throughout the mitotic (M) phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome inhibitors, and the regulation of mitotic exit and cytokinesis.

PLK1 is ubiquitously expressed in normal proliferating tissues and is over-expressed in a wide variety of human tumors (including lung, colon, prostate, ovary, breast, and head and neck squamous cell carcinoma).

Onvansertib was developed to have high selectivity for PLK1, to be administered orally, and to have a relatively short drug half-life of approximately 24 hours compared to previous pan Polo-like inhibitors.

Onvansertib has been tested in-vivo in different xenograft and transgenic models at times suggesting tumor growth inhibition or tumor regression.

A Phase 1 safety study was successfully completed in patients with advanced metastatic solid tumors and published in 2017 in Investigational New Drugs .

We have three active Investigational New Drug (“IND”) applications in place with the U.S.

Food and Drug Administration (“FDA”), and three ongoing clinical studies.The first study is TROV-052 (ClinicalTrials.gov Identifier NCT03303339), a Phase 1b/2 open-label clinical trial of onvansertib in combination with standard-of-care low-dose cytarabine (“LDAC”) or decitabine for patients with relapsed or refractory AML.

We have four active Investigational New Drug (“IND”) applications in place with the U.S.

Food and Drug Administration (“FDA”), and three ongoing clinical studies.

The first study is TROV-052 (ClinicalTrials.gov Identifier NCT03303339), a Phase 1b/2 open-label clinical trial of onvansertib in combination with standard-of-care low-dose cytarabine (“LDAC”) or decitabine for patients with relapsed or refractory AML.

The second study is TROV-053 (ClinicalTrials.gov Identifier NCT03414034), a Phase 2 open-label clinical trial of onvansertib in combination with Zytiga ® (abiraterone acetate)/prednisone, all administered orally, for patients with metastatic Castration-Resistant Prostate Cancer (“mCRPC”).

The third study is TROV-054 (ClincalTrials.gov Identifier NCT03829410), a Phase 1b/2 open-label clinical trial of onvansertib in combination with FOLFIRI (folinic acid, fluorouracil and irinotecan) and Avastin ® (bevacizumab) for patients with mCRC, who have a KRAS mutation.

A new Phase 2 trial of onvansertib in combination with nanoliposomal irinotecan, leucovorin and fluorouracil for the second-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is planned for initiation in the first half of 2021 (ClinicalTrials.gov Identifier NCT04752696)

Development of onvansertib, as part of a combination regimen with already approved drugs, has the potential to bring new treatment options to patients across a wide array of cancers.

Onvansertib has shown preclinical antitumor activity as a single agent and synergy (interaction of discrete drugs such that the total effect is greater than the sum of the individual effects) in combination with numerous different chemotherapeutics and targeted therapies, such as Zytiga ® (abiraterone acetate), Avastin ® (bevacizumab), Camptosa ® (irinotecan), Gemzar ® (gemcitabine), Beleodaq ® (belinostat), Venclexta ® (venetoclax), quizartinib (AC220), a development stage FLT3 inhibitor, Taxol ® (paclitaxel), and Velcade ® (bortezomib) in AML, mCRPC, mCRC and other hematologic and solid tumor cancers.

On October 18, 2017, we announced results of preclinical research indicating potential synergy of onvansertib with abiraterone acetate in C4-2 prostate cancer cells.

This synergy assessment study was conducted by Dr.

Michael Yaffe M.D., Ph.D.

FACS, and David H.

Koch Professor of Biology and Biological Engineering at Massachusetts Institute of Technology (“MIT”).

The results appeared to indicate that the combination of onvansertib with Zytiga ® (abiraterone) decreased cell

viability in mCRPC tumor cells and the apparent synergy observed was greater than the expected effect of combining the two drugs.

Zytiga ® is indicated for use in combination with prednisone for the treatment of patients with mCRPC who have received prior chemotherapy containing docetaxel.

We believe there is an unmet medical need to improve on the resistance to hormone therapy and extend the benefit of response to abiraterone for mCRPC patients.

On April 23, 2019, we announced results of preclinical research demonstrating synergy of onvansertib in combination with Venclexta ® (venetoclax) in a cell model of venetoclax-resistance AML.

The data further supports our ongoing onvansertib clinical development program in patients with relapsed or refractory AML.

We believe there is an opportunity to treat patients, who have relapsed following first-line treatment with venetoclax, with onvansertib in combination with a hypomethylating agent such as decitabine or azacytadine.

Onvansertib has been evaluated preclinically in combination with several different chemotherapies, including irinotecan, cisplatin, cytarabine, doxorubicin, gemcitabine and paclitaxel, and with targeted therapeutics such as abiraterone, histone deacetylase (HDAC) inhibitors, fms-like tyrosine kinase 3 (FLT3) inhibitors, and bortezomib.

These therapies are used clinically for the treatment of many hematologic and solid cancers, including acute myeloid leukemia (AML), non-Hodgkin’s lymphoma (NHL), metastatic CRC, metastatic castration resistant prostate cancer (mCRPC), adrenocortical carcinoma (ACC), triple negative breast cancer (TNBC), small cell lung cancer (SCLC), and ovarian cancer.

Our strategy includes integrating a predictive clinical biomarker approach into our onvansertib clinical development programs, which we believe may enable us to tailor treatment to specific sub-populations of patients who are most likely to respond and have a positive clinical impact.

PLK1 uniquely phosphorylates translational control tumor protein (“TCTP”) to form pTCTP and inhibition of this enzymatic activity by onvansertib appears to be predictive of patient response to treatment.

Onvansertib Phase 1 Safety Study in Solid Tumors

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No GI disorders, mucositis, or alopecia was observed, confirming that bone marrow cells are the most sensitive to onvansertib inhibition with the applied dosing schedule.

We are utilizing the existing IND applications to develop onvansertib in solid tumors as part of our clinical development expansion plans, with our initial focus in mCRPC and mCRC.

We are utilizing the existing IND applications to develop onvansertib in solid tumors as part of our clinical development expansion plans, with our initial focus in mCRC and mCRPC.

Onvansertib Phase 2 Study in metastatic Castration-Resistant Prostate Cancer

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The trial will enroll up to 44 patients to assess the safety and preliminary efficacy of the combination regimen.

This ongoing Phase1b/2 clinical study is being conducted at two prestigious cancer centers:

The Phase1b segment of this clinical study has been conducted at two prestigious cancer centers:

USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

Heinz-Josef Lenz, Associate Director for Clinical Research and Co-Leader of the Gastrointestinal Cancers Program at the USC Norris Comprehensive Cancer Center, is the principal investigator for the Phase 1b/2 mCRC trial.

The Phase 2 segment is being conducted at USC Norris Comprehensive Cancer Center, the Mayo Clinic (Arizona, Minnesota and Florida), Kansas University Medical Center and CARTI Cancer Research.

Onvansertib Phase 1b/2 Study in Acute Myeloid Leukemia

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Phase 1b is a dose escalation trial to evaluate the safety, tolerability, dose and scheduling of onvansertib, and to determine a recommended clinical treatment dose for the Phase 2 continuation trial.

Pharmacokinetics of onvansertib and correlative biomarker activity will be assessed throughout the Phase 1b and Phase 2 segments of the trial.

Enrollment of Phase 2 was completed in 2020.

Pharmacokinetics of onvansertib and correlative biomarker activity have been assessed throughout the Phase 1b and Phase 2 segments of the trial.

The Phase 2 continuation trial is open-label with administration of the recommended onvansertib clinical dose in combination with standard-of-care chemotherapy to further evaluate safety and assess efficacy.

Doses of onvansertib will be administered orally each day on Days 1-5, in a 21-28-day cycle in both Phase 1b and Phase 2.

In 2019, we completed the Phase 1b segment of this trial and began enrolling patients in Phase 2.

In 2019, we completed the Phase 1b segment of this trial and enrollment in Phase 2 was completed in October 2020.

A total of eight sites are conducting this trial, which is being led by Hematologist Amer Zeidan, MBBS, MHS, Assistant Professor of Medicine at Yale School of Medicine, Hematology expert at Yale Cancer Center.

Optimizing Drug Development with Correlative Biomarker Analysis using Circulating Tumor DNA

We have significant experience and expertise with biomarkers and technology in cancer, including CRC and AML.

We are using our Precision Cancer Medicine TM (“PCM TM ”) technology to measure PLK1 enzymatic activity to potentially identify patients most likely to respond to onvansertib and to measure patient therapy response.

The TCTP is phosphorylated by PLK1 at residue serine 46 (pTCTP) and has been shown to be a specific marker of PLK1 activity in-vivo in preclinical models.

In our ongoing clinical trial in AML, we validated that pTCTP and TCTP are present and can be detected by capillary Western-Blot (“WB”) in peripheral blood mononuclear cells (“PBMC”) isolated from healthy donors and AML patients, 24-hours after blood collection.

As an exploratory objective of the Phase 1b segment of the trial, we are assessing the extent of PLK1 inhibition by onvansertib in patients receiving treatment and plan to use this information and methodology going forward in the Phase 2 continuation trial, and beyond.

We have significant experience and expertise with biomarkers and technology in cancer.

In our ongoing clinical trial in KRAS-mutated mCRC, we are quantitatively assessing changes in the KRAS mutational burden with a simple blood test.

Decreases in KRAS are highly predictive of radiographic response observed as tumor regression.

Decreases in KRAS mutant allelic frequency (MAF) after the first cycle of treatment are highly predictive of subsequent radiographic response observed as tumor shrinkage.

Technological advancements in the molecular characterization of cancers have enabled researchers to identify an increasing number of key molecular drivers of cancer progression.

These discoveries have led to multiple novel anticancer therapeutics and clinical benefit in selected patient populations.

As a clinical-stage oncology therapeutics company developing targeted therapies to treat leukemias, lymphomas and solid tumor cancers, our objective is to optimize drug development by using our proprietary PCM TM expertise and biomarker strategy as part of our approach.

Our laboratory in San Diego, California, enables us to use our technology platform to optimize drug development and patient care.

As a clinical-stage biotechnology company developing new treatment options for cancer patients in indications with the greatest medical need, our objective is to optimize drug development by using our biomarker strategy as part of our approach.

Our laboratory in San Diego, California, enables us to optimize drug development and patient care.

In the clinical development of our drug candidate, onvansertib, correlative biomarker analyses are being used to help inform decisions in the evaluation of dose-response and optimal regimen for desired pharmacologic effect and safety.

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Therefore, geographic information is not presented for revenues or long-lived assets.

We are a clinical-stage oncology therapeutics company with our primary focus on the development of our drug candidate, onvansertib, a first-in-class, third generation, oral and highly-selective PLK1 inhibitor to treat leukemias, lymphomas and solid tumor cancers.

We are a clinical-stage biotechnology company with our primary focus on the development of our drug candidate, onvansertib, a first-in-class, third generation, oral and highly selective PLK1 inhibitor to treat solid tumor cancers and hematologic malignancies.

There have been several drug candidates in this class of targeted oncology therapeutics to enter clinical trials;

however, we believe onvansertib is the only candidate currently in clinical trials and is differentiated from other ATP competitive inhibitors in that:

however, we believe onvansertib is the only oral candidate currently in clinical trials and is differentiated from other ATP competitive inhibitors in that:

• its inhibition of PLK1 is highly-selective and the half maximal inhibitory concentration (IC 50 ) for PLK2 and PLK3 is over 5,000-fold of that for PLK1;

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The unacceptable toxicity of prior PLK inhibitors, such as volasertib from Boehringer Ingelheim, may be due to non-selective inhibition of PLK2 and PLK3 and a much longer half-life (approximately 135 hours) that could result in drug accumulation, which ultimately may have led to unsatisfactory clinical and safety outcomes.

We believe the efficacy of PLK1 inhibition in AML has already been shown in the proof-of-concept trial of volasertib.

Therefore, onvansertib’s highly-selective activity, oral dosing and short half-life could enable favorable efficacy and safety with potential survival benefits in AML patients with relapsed/refractory disease or newly-diagnosed disease and ineligible for intensive induction therapy.

In 2018, we initiated a Phase 1b/2 open-label clinical trial of onvansertib in combination with standard-of-care chemotherapy in AML patients to evaluate the safety/tolerability, determine the maximum tolerated dose (“MTD”), and assess preliminary efficacy.

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This study is on file at ClinicalTrials.gov with the Identifier NCT03829410.

As such, we have three active IND applications in place with the FDA, one with the hematologic division and two with the solid tumor division.

This enables us to quickly initiate additional clinical trials of our drug candidate, onvansertib, in leukemias, lymphomas and solid tumor cancers.

As of December 2020 we have four active IND applications in place with the FDA, one with the hematologic division and three with the solid tumor division.

This enables us to quickly initiate additional clinical trials of our drug candidate, onvansertib, in solid tumor cancers and hematologic malignancies.

Drug Development and Monitoring of Therapeutic Outcomes

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By measuring specific genetic markers, it may be possible to pre-identify, and subsequently screen for, the most likely responders to the therapy, and to limit patient recruitment to this subset.

This strategy could significantly reduce the cost to develop a drug and improve development time lines.

We believe that there is significant research potential for our PCM TM technology to be incorporated into these clinical trial protocols, and ultimately into post-approval patient identification protocols.

This strategy could significantly reduce the cost to develop a drug and improve development timelines.

We believe that there is significant research potential technology and expertise to be incorporated into ongoing and future clinical trial protocols, and ultimately into post-approval patient identification protocols.

Our Business Strategy

We are a clinical-stage, oncology therapeutics company, taking a precision medicine approach to target cancers with a need for new treatment options, including KRAS-mutated mCRC, mCRPC and AML.

By integrating biomarkers into our clinical development programs, we believe we will be able to identify patients who are most likely to respond to treatment.

Specifically, we are developing drugs that target mitosis (cell division) to treat a variety of cancers and associated indications.

Our intellectual property and proprietary technology enables us to analyze ctDNA and clinically actionable markers for predicting response to cancer therapies.

By integrating

biomarkers into our clinical development programs, we believe we will be able to identify patients who are most likely to respond to treatment.

Specifically, we are developing onvansertib, a first-in-class, third generation PLK1 inhibitor that targets mitosis (cell division) to treat a variety of cancers and associated indications.

Research and Development

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Intellectual Property

We consider the protection of our proprietary technologies and products, as well as our ability to maintain patent protection intended to cover the composition of matter of our product candidates, their methods of use, and other related technology and inventions, to be a critical element in the success of our business.

As of December 31, 2019 , our wholly-owned and licensed intellectual property included 62 issued patents and 13 pending patent applications in the U.S.

The pending applications include multiple international applications filed under the Patent Cooperation Treaty (“PCT applications”) that may be used as the basis for multiple additional patent applications.

We consider the protection of our proprietary technologies and products, as well as our ability to maintain patent protection that covers the composition of matter of our product candidates, their methods of use, and other related technologies and inventions, to be a critical element in the success of our business.

As of December 31, 2020, our owned and licensed intellectual property included 57 issued patents and 11 pending patent applications in the U.S.

The pending patent applications include multiple international patent applications filed under the Patent Cooperation Treaty that may be used as the basis for multiple additional patent applications worldwide.

We plan to protect our intellectual property position by, among other things, licensing or filing our own U.S.

and foreign patent applications related to our proprietary technology, and any inventions or improvements that are important to the development and implementation of our business.

and foreign patent applications related to our proprietary technologies and products, and any inventions or improvements that are important to the development and implementation of our business.

We also may seek patent protection, if available, with respect to biomarkers and diagnostic methods that may be used to determine optimal patient populations for use of our product candidates.

Our license agreement related to onvansertib grants us exclusive, worldwide licenses under a portfolio of patents covering three broad areas:

(1) Directed to onvansertib, related compounds and processes for making compounds;

Our license agreement with Nerviano dated March 15, 2017 grants us exclusive, worldwide licenses under a portfolio of three patent families of U.S.

and foreign patents covering three broad areas:

(1) onvansertib (composition of matter), related compounds and processes for making compounds;

pharmaceutical compositions and methods of treating diseases characterized by dysregulated protein kinase activity;

(2) Directed to salts and pharmaceutical compositions of onvansertib;

(2) salts and pharmaceutical compositions of onvansertib;

methods of treating mammals in need of PLK inhibition;

and (3) Directed to synergistic combinations of onvansertib and one or more of a broad range of antineoplastic agents, and pharmaceutical compositions of those combinations.

Members of this patent group expire between 2026 and 2029.

On October 11, 2017, we entered into a Patent Option Agreement with MIT for the exclusive rights to negotiate a royalty-bearing, limited-term exclusivity license to practice world-wide patent rights to US Patent 9,566,280, subject to the rights of MIT (research, testing, and educational purposes), Ortho McNeil Pharmaceuticals-Janssen Pharmaceuticals and its Affiliates (internal research and pre-clinical drug development purposes including some laboratory research) and the federal

government (government-funded inventions claimed in any patent rights and to exercise march in rights).

This patent is generally directed to combination therapies including an antiandrogen or androgen antagonist and polo-like kinase inhibitor for the treatment of cancer.

On September 19, 2018, we entered into an Exclusive Patent License Agreement with MIT for combination therapy for anti-androgens and Polo-like kinase inhibitors in prostate cancer.

The patent agreement covers the rights to develop combination therapies and identified predictive clinical biomarkers across cancer types, expanding potential indications for onvansertib.

Under the agreement, Trovagene has exclusive rights to develop combination therapies that include anti-androgen or androgen antagonist and a PLK inhibitor for the treatment of cancer.

and (3) synergistic combinations of onvansertib and one or more of a broad range of antineoplastic agents, and pharmaceutical compositions of those combinations.

Patents of this licensed portfolio will expire between 2027 and 2030.

patents of this licensed patent portfolio will expire in 2030, with patent term extension up to 2035.

On September 19, 2018, we entered into an Exclusive Patent License Agreement with MIT to a patent family directed to combination therapies including an antiandrogen or androgen antagonist and a polo-like kinase inhibitor (such as onvansertib) for the treatment of cancer.

The license agreement covers the rights to develop combination therapies and identified predictive clinical biomarkers across cancer types, expanding potential indications for onvansertib.

Under the agreement, Cardiff Oncology has exclusive rights to develop, make, use, and sell combination therapies that include an anti-androgen or androgen antagonist and a PLK inhibitor for the treatment of cancer.

The exclusive license agreement is part of our strategy to explore the efficacy of onvansertib in combination with anti-androgen drugs in cancers including prostate, breast, pancreatic, lung and gastrointestinal.

On January 23, 2019, we announced the issuance of a new patent (10,155,006), entitled Combination Therapies and Methods of Use Thereof for Treating Cancer, by the U.S.

Patent and Trademark Office (“USPTO”).

This patent broadens previously issued patent (9,566,280), by expanding the use of onvansertib to encompass combination therapies with any anti-androgen and androgen antagonist drug, such as Zytiga, Xtandi and Erleada for the treatment of metastatic and non-metastatic castrate-resistant prostate cancer.

Another group of patents and patent applications are directed to various methods relating to detecting nucleic acid sequences in urine and nucleic acid modifications and alterations in urine;

detecting and monitoring cancer through urine-based testing, nucleic acid screening, and monitoring in cases of transplantation and infectious diseases, detecting specific gene mutations and indicators of disease (including NPM1 mutations).

Applications are also pending to protect proprietary methods of collecting, extracting, detecting and enriching small concentrations of short nucleic acid sequences, and detecting and monitoring mutations in diseases, such as cancer, over time.

Members of this patent group expire between 2021 and 2036.

The licensed MIT patent family includes U.S.

9,566,280, 10,155,006, and 10,772,898, which will expire in 2035, with patent term extension up to 2040.

9,566,280 encompasses using abiraterone in combination with onvansertib to treat cancer.

10,155,006 and 10,772,898 broaden previously issued U.S.

9,566,280, by expanding the use of onvansertib to encompass combination therapies with any anti-androgen and androgen antagonist drug, such as Zytiga®, Xtandi® and Erleada® for the treatment of metastatic and non-metastatic castrate-resistant prostate cancer.

Our owned intellectual property included eight patent families related to onvansertib.

These families include patent applications directed to treating cancer using PLK1 inhibitors and determining efficacy of the treatment, treating benign prostatic hyperplasia using onvansertib, treating prostate cancer using PLK1 inhibitors, determining efficacy of PLK1 treatment based on biomarkers, and treating leukemia and lymphoma using combination therapies including a B-cell lymphoma 2 and a PLK1 inhibitor.

Any patents issued in these families will expire between 2039 and 2041.

Wherever possible, we seek to protect our inventions by filing U.S.

patents as well as foreign counterpart applications in select other countries.

patent applications as well as foreign counterpart applications in select countries.

Because patent applications in the U.S.

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In addition to patent protection, we also rely on know-how, trade secrets and the careful monitoring of proprietary information, all of which can be difficult to protect.

We seek to protect some of our proprietary technology and processes by entering into confidentiality agreements with our employees, consultants, and contractors.

We seek to protect some of our proprietary technologies and processes by entering into confidentiality agreements with our employees, consultants, and contractors.

These agreements may be breached, we may not have adequate remedies for any breach and our trade secrets may otherwise become known or be independently discovered by competitors.

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Manufacturing and Distribution

We have a supplier agreement with NerPharMa, S.r.l., a GMP and FDA validated pharmaceutical manufacturing company and a subsidiary of Nerviano, to manufacture drug product for onvansertib.

We have a supply agreement with NerPharMa, S.r.l., a GMP and FDA validated pharmaceutical manufacturing company and a subsidiary of Nerviano, to manufacture drug product for onvansertib.

The agreement covers the clinical and commercial supply of onvansertib, and includes both Active Pharmaceutical Ingredients (“API”) and Good Manufacturing Process (“GMP”) production of capsules.

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Additionally, the FDA will inspect the facility or the facilities at which the drug product is manufactured.

The FDA will not approve the NDA or, in the case of a biologic, the BLA unless compliance with cGMPs is satisfactory and the marketing application contains data that provide substantial evidence that the product is safe and effective in the indication studied.

The FDA will not approve the NDA or, in the case of a biologic, the BLA unless compliance with Current Good Manufacturing Process ("CGMPs") is satisfactory and the marketing application contains data that provide substantial evidence that the product is safe and effective in the indication studied.

Manufacturers of biologics also must comply with FDA’s general biological product standards.

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The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

It is not unusual for the FDA to issue a complete response letter because it believes that the drug product is not safe enough or effective enough or because it does not believe that the data submitted are reliable or conclusive.

It is not unusual for the FDA to issue a complete response letter

because it believes that the drug product is not safe enough or effective enough or because it does not believe that the data submitted are reliable or conclusive.

An approval letter authorizes commercial marketing of the drug product with specific prescribing information for specific indications.

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The term “remuneration” has been broadly interpreted to include anything of value.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers on the other hand.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and

prescribers, purchasers, and formulary managers on the other hand.

Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution, the exemptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases, or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor.

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HIPAA, as amended by the Health Information Technology and Clinical Health Act of 2009 (“HITECH”) and its implementing regulations, which impose certain requirements relating to the privacy, security, transmission and breach reporting of individually identifiable health information upon entities subject to the law, such as health plans, healthcare clearinghouses and healthcare providers and their respective business associates that perform services for them that involve individually identifiable health information.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to

file civil actions for damages or injunctions in U.S.

federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

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Because of the breadth of these laws and the narrowness of the safe harbors, it is possible that some business activities can be subject to challenge under one or more of such laws.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent

and regulations.

Federal and state enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry.

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Some of the provisions of the PPACA have yet to be implemented, and there have been legal and political challenges to certain aspects of the PPACA.

Since January 2017, President Trump has signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the PPACA.

During President Trump's administration, he signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the PPACA.

Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the PPACA.

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In addition, given recent federal and state government initiatives directed at lowering the total cost of healthcare, Congress and state legislatures will likely continue to focus on healthcare reform, the cost of prescription drugs and biologics and the reform of the Medicare and Medicaid programs.

While no one can predict the full outcome of any such legislation, it may result in decreased reimbursement for drugs and biologics, which may further exacerbate industry-wide pressure to reduce

prescription drug prices.

While no one can predict the full outcome of any such legislation, it may result in decreased reimbursement for drugs and biologics, which may further exacerbate industry-wide pressure to reduce prescription drug prices.

This could harm a pharmaceutical manufacturer’s ability to generate revenue.

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Onvansertib is not the first PLK inhibitor that has entered clinical development;

however, we believe it currently is the only oral PLK1 inhibitor in active clinical development and delivers highly-selective PLK1 inhibition, which suggests that it could demonstrate survival benefits in relapsed or refractory AML patients without the adverse events that have prohibited the advancement of other PLK1 inhibitors.

Onvansertib is also synergistic in combination with numerous chemotherapies and targeted therapeutics and may enhance and/or extend response to treatment across a number of hematologic and solid tumor cancers.

however, we believe it currently is the only oral PLK1 inhibitor in active clinical development and delivers highly selective PLK1 inhibition.

Onvansertib is also synergistic in combination with numerous chemotherapies and targeted therapeutics and may enhance and/or extend response to treatment across a number of solid tumor cancers and hematologic malignancies.

A Phase 1 trial in advanced metastatic solid tumor cancers has been completed and published in Investigational New Drugs .

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A Phase 2 trial in mCRPC was initiated in June, 2018 with the Harvard Medical Cancer Centers - Beth Israel Deaconess Medical Center, Dana Farber Cancer Institute and Massachusetts General Hospital - with the first patient treated in August, 2018.

A Phase 1b/2 trial in mCRC was initiated in July, 2019 with USC Norris Comprehensive Cancer Center and The Mayo Clinic - with the first patient treated in August, 2019.

A Phase 1b/2 trial in mCRC was initiated in July, 2019 with USC Norris Comprehensive Cancer Center and The Mayo Clinic (Arizona) - with the first patient treated in August, 2019.

At the end of 2020 and early 2021, five additional sites were added including The Mayo Clinics (Minnesota and Florida), CARTI Cancer Center, Kansas University Medical Center and Inova Schar Cancer Institute.

The most prominent PLK inhibitor tested in late-stage clinical development, thus far, is volasertib, developed by Boehringer Ingelheim.

In a randomized Phase 2 trial of volasertib plus LDAC in 87 AML patients not eligible for induction therapy, patients received LDAC 20mg twice-daily subcutaneously on days 1-10 or LDAC plus volasertib 350 mg IV on days 1

+ 15 every four weeks.

The response rate (complete remission and complete remission with incomplete blood count recovery) was higher for LDAC + volasertib vs LDAC (31.0% vs 13.3%;

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The trial was completed in 2009 and there are no further clinical updates for GSK461364 after the Phase 1 study.

Other PLK inhibitors that have been evaluated include rogosertib - Oncova, a non-targeted broad-spectrum multi-kinase inhibitor (RAF, PI3K, PLK), evaluated for pancreatic cancer and Myelodysplastic Syndrome (“MDS”), which failed a Phase 3 trial in MDS.

Currently, Oncova is testing an IV formulation of rogosertib in high-risk MDS patients.

CY140 - Cyclacel, a PLK1, 2, 3 inhibitor, is currently in preclinical studies for the treatment of esophageal cancer.

Other PLK inhibitors that have been evaluated include rigosertib (Oncova) and CY140 (Cyclacel).

Rigosertib, a non-targeted broad-spectrum multi-kinase inhibitor (RAF, PI3K, PLK), was evaluated for myelodysplastic syndrome (“MDS”), and failed to achieve the primary endpoint of overall survival in a Phase 3 trial (2020).

CY140, an inhibitor of PLK1, PLK2 and PLK3, is currently in a phase 1 first-in-human study for advanced leukemias and MDS (2020).

Human Capital

The human capital objectives we focus on in managing our business include attracting, developing, and retaining key personnel.

Our employees are critical to the success of our organization and we are committed to supporting our employees’ professional development.

We believe our management team has the experience necessary to effectively implement our growth strategy and continue to drive shareholder value.

We provide competitive compensation and benefits to attract and retain key personnel, while also providing a safe, inclusive and respectful workplace.

As of February 18, 2021, we had a total of 12 employees, 11 of whom were full-time.

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In May 2012, our common stock was listed on The Nasdaq Capital Market under the ticker symbol TROV.

Our corporate website address is www.trovageneoncology.com.

Our annual reports on Form 10-K, quarterly reports on Form 10-Q, proxy statements, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge at www.trovageneoncology.com as soon as reasonably practicable after electronically filing such reports with the Securities and Exchange Commission.

In May 2020 we changed our name to Cardiff Oncology, Inc.

and our Nasdaq ticker symbol changed to CRDF.

Our corporate website address is www.cardiffoncology.com.

Our annual reports on Form 10-K, quarterly reports on Form 10-Q, proxy statements, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge at www.cardiffoncology.com as soon as reasonably practicable after electronically filing such reports with the Securities and Exchange Commission.

Any information contained on, or that can be accessed through, our website is not incorporated by reference into, nor is it in any way a part of, this Annual Report on Form 10-K.

These reports are also available at www.sec.gov.

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-K

Item 1. Business