UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): September 10, 2022
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Registrant’s telephone number, including area code: (858) 952-7570
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Item 8.01 Regulation FD Disclosure
On September 12, 2022, Cardiff Oncology, Inc. (the “Company”) issued a press release announcing plans to conduct a randomized Phase 2 trial of onvansertib in combination with standard-of-care (SoC) FOLFIRI/bevacizumab in second-line RAS-mutated mCRC, durability of responses from its ongoing Phase 1b/2 clinical trial in KRAS-mutated mCRC and additional business updates. A copy of the press release is furnished as Exhibit 99.1 to this Form 8-K. In addition, on September 12, 2022, the Company held a conference call and webcast providing a clinical and corporate update and presented the Investor Presentation attached hereto as Exhibit 99.3 and incorporated herein by reference.
The information under this Item 7.01, including Exhibits 99.1 and 99.3, shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of such section, and shall not be deemed to be incorporated by reference into the filings of the Company under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.
Item 8.01 Other Events.
On September 10, 2022, the Company issued a press release announcing new preclinical and clinical data from its program in KRAS-mutated mCRC. The data are featured in two posters being presented at the European Society for Medical Oncology (ESMO) Congress 2022, which is taking place at the Paris Expo Porte de Versailles in Paris, France, and virtually. A copy of the press release is furnished as Exhibit 99.2 to this Form 8-K.
Item 9.01. Financial Statements and Exhibits
(d) Exhibits.
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Dated: September 12, 2022
| CARDIFF ONCOLOGY, INC. | ||||||||
| By: | /s/ Mark Erlander | |||||||
| Mark Erlander | ||||||||
| Chief Executive Officer | ||||||||
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Cardiff Oncology Announces New Preclinical and Clinical Data from Program in KRAS-mutated Metastatic Colorectal Cancer (mCRC) at the ESMO Congress 2022
Durable responses to treatment, with a median duration of response (mDoR) of 11.7 months, reported in Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC
Observed mDoR is supported by preclinical findings that demonstrate onvansertib in combination with irinotecan can overcome intrinsic and refractory resistance to irinotecan in patient-derived xenograft models
Patients with a ≥90% decrease in KRAS mutant allele frequency (MAF), a response biomarker, in the first cycle of treatment had significantly higher ORR and longer PFS in Phase 1b/2 trial and an Expanded Access Program (EAP)
SAN DIEGO, September 10, 2022 – Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced new preclinical and clinical data from its program in KRAS-mutated mCRC. The data are featured in two posters being presented at the European Society for Medical Oncology (ESMO) Congress 2022, which is taking place at the Paris Expo Porte de Versailles in Paris, France, and virtually.
Poster 397P: Early Decreases in KRAS Mutant Allele Frequency (MAF) Predict Clinical Benefit to the PLK1 Inhibitor Onvansertib in Combination with FOLFIRI/bev in 2L Treatment of Metastatic Colorectal Carcinoma (mCRC)
Poster 397P includes updated data (data cut-off date: July 25, 2022), as well as the results of correlative biomarker analyses from a Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC. Measures of clinical response were compared between subsets of patients defined as KRAS responders or non-responders. KRAS responders were defined as patients with a ≥90% decrease in KRAS mutant allele frequency (MAF) in circulating tumor DNA (ctDNA) after one treatment cycle.
“The data from this trial show onvansertib plus FOLFIRI and bevacizumab outperforming historical controls on multiple key endpoints and are highly encouraging,” said Heinz-Josef Lenz, MD, FACP, professor of medicine at USC Norris Comprehensive Cancer Center and the trial’s principal investigator. “They suggest trial participants with various KRAS mutations experience durable clinical benefits and that the onvansertib-FOLFIRI combination is avoiding the mechanisms that typically drive rapid acquired resistance to the standard-of-care (SoC). This highlights onvansertib’s potential to fill a crucial gap in mCRC’s therapeutic paradigm, as there are currently limited options available for second line patients. In addition, the significant increases between response rates and progression-free survival in KRAS responders point to changes in MAF as a potential blood-based biomarker that could aid in treatment decisions.”
Key data and conclusions presented in the poster include:
Overall response rate (ORR) and median progression-free survival (mPFS) reported in Phase 1b/2 trial substantially exceed those reported in historical control trials
•ORR across all evaluable patients was 35%, with 17 of 48 evaluable patients achieving an objective response and responses have been observed across multiple KRAS variants
•Median duration of response (mDoR) across all evaluable patients was 11.7 months (95% confidence interval (CI): 8.9 – not reached)
•mPFS across all evaluable patients was 9.3 months (95% CI: 7.6 – 13.5)
•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 – 5.7 months, respectively1-4
KRAS responders showed significantly greater ORR and mPFS compared to non-responders
•ORR in KRAS responders vs. KRAS non-responders: 63.6% (14/22) vs. 8.7% (2/23) (p = 0.00014)
•mPFS in KRAS responders vs. KRAS non-responders: 12.6 months vs. 6.0 months (p=0.019)
Poster 366P: The PLK1 Inhibitor Onvansertib Overcomes Irinotecan Resistance in RAS-mutated Metastatic Colorectal Cancer (mCRC) In Vivo and in Patients
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Poster 366P includes findings (as of August 5, 2022) from Cardiff Oncology’s EAP of onvansertib in KRAS-mutated mCRC, as well as data from murine studies evaluating onvansertib in combination with irinotecan in 6 PDX models of irinotecan-resistant, RAS-mutated CRC. Clinical findings reported in the Expanded Access Program (EAP) were compared between KRAS responders and non-responders. To enroll in the EAP, a patient must have been ineligible for the Phase 1b/2 clinical trial having received prior treatment with irinotecan or failed or progressed on multiple prior lines of standard-of-care therapy. EAP patients are treated with the same treatment regimen (onvansertib 15 mg/m2 plus FOLFIRI and bevacizumab) and dosing schedule as patients in the Phase 1b/2 clinical trial.
Scott Kopetz, MD, PhD, FACP, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center commented, “Currently available third-line or later treatment options for patients are severely limited, due in large part to the high prevalence of tumors that show resistance to irinotecan. Based on the findings being presented at ESMO, combining onvansertib with the current SOC appears to be an innovative strategy that can overcome irinotecan resistance and address a broad and pressing unmet need. This hypothesis is further supported by onvansertib’s mechanism of action, which targets DNA damage repair pathways underlying resistance to irinotecan and other chemotherapeutic agents.”
Key findings and conclusions presented in the poster include:
EAP patients with prior irinotecan treatment (43 out of a total of 51 EAP patients) showed clinical benefit following treatment with onvansertib plus FOLFIRI/bevacizumab
•mPFS was 4.04 months (95% CI: 2.96 – 8.38); 6-month PFS rate was 37.3% (95% CI: 24.9 – 55.8)
Of EAP patients with prior irinotecan treatment, KRAS responders had significantly longer PFS compared to non-responders.
•mPFS in KRAS responders vs. KRAS non-responders: 11.18 months vs. 3.25 months (p=0.0014)
The combination of onvansertib and irinotecan showed significantly greater anti-tumor activity compared to onvansertib monotherapy in 5 of 6 tested PDX models of irinotecan-resistant, RAS-mutated CRC.
The ESMO posters are currently available for viewing on the congress’s virtual platform and will also be presented by Drs. Lenz and Kopetz during Poster Sessions 8 and 7, respectively, on September 11, 2022. Following the congress, the posters will be available on the "Scientific Presentations" section of the Cardiff Oncology website at https://cardiffoncology.com/scientific-presentations/.
Clinical and Corporate Update Conference Call and Webcast
Cardiff Oncology will host a webcast and conference call to provide a clinical and corporate update to the investment community on Monday, September 12, 2022 at 4:30 PM ET. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.
About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin® (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.
About the EAP for Onvansertib in KRAS-mutated mCRC
Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-
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mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI and bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the second line eligibility criteria for enrollment in the clinical trial. The program has reached capacity and is no longer open to enrollment.
References:
1.Giessen et al., Acta Oncologica 2015, 54: 187-193
2.Cremolini et al., Lancet Oncol 2020, 21: 497–507
3.Antoniotti et al., Correspondence Lancet Oncol June 2020
4.Bennouna et al., Lancet Oncol 2013; 14: 29–37
About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SOC) therapeutics in clinical programs targeting indications such as KRAS-mutated metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma, and metastatic castrate-resistant prostate cancer. These programs and our broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SOC. For more information, please visit https://www.cardiffoncology.com.
Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
Cardiff Oncology Contact:
James Levine
Chief Financial Officer
858-952-7670
jlevine@cardiffoncology.com
Chief Financial Officer
858-952-7670
jlevine@cardiffoncology.com
Investor Contact:
Joyce Allaire
LifeSci Advisors
212-915-2569
jallaire@lifesciadvisors.com
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Media Contact:
Amy Jobe, Ph.D.
LifeSci Communications
315-879-8192
ajobe@lifescicomms.com
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Cardiff Oncology Announces Plans for a Randomized Trial in Metastatic Colorectal Cancer (mCRC), Durability of Responses in Ongoing Phase 1b/2 Trial in mCRC and Additional Business Updates
Next trial in RAS-mutated mCRC (ONSEMBLE) is a randomized Phase 2 trial to demonstrate onvansertib’s contribution to SoC and position for a possible accelerated approval opportunity; topline data expected in 2H 2024
Data from ongoing Phase 1b/2 trial in KRAS-mutated mCRC show durable responses to treatment, with a median duration of response (mDoR) of 11.7 months for all doses and 12.5 months for the recommended phase 2 dose
Initial data in Phase 2 trial in second-line pancreatic ductal adenocarcinoma (mPDAC) show 1 partial response (PR), 3 stable disease (SD) achieved in 5 evaluable patients treated with onvansertib plus SoC
Based on its current expectations and projections, the Company’s current cash resources are sufficient to fund its operations into 2025
Company management is hosting a webcast and conference call today at 4:30 PM ET
SAN DIEGO, September 12, 2022 – Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced plans to conduct a randomized Phase 2 trial of onvansertib in combination with standard-of-care (SoC) FOLFIRI/bevacizumab in second-line RAS-mutated mCRC, durability of responses from its ongoing Phase 1b/2 clinical trial in KRAS-mutated mCRC and additional business updates.
“We designed our next clinical program in mCRC, a randomized Phase 2 trial we have named ONSEMBLE, to accelerate and de-risk our lead indication,” said Mark Erlander, PhD, chief executive officer of Cardiff Oncology. “Chief among ONSEMBLE’s objectives is to generate a randomized dataset to demonstrate the contribution of onvansertib over standard-of-care alone, validating the Phase 1b/2 trial results. These results show patients with different KRAS mutations experiencing durable responses to treatment with onvansertib plus standard-of-care, with an objective response rate and median progression-free survival that are well above historical benchmarks. In line with the FDA’s Project Optimus initiative, the ONSEMBLE trial will also seek to confirm the optimal dose of onvansertib in mCRC. We believe achieving these objectives could position onvansertib for a possible accelerated approval opportunity, though this would ultimately depend on the strength of the ONSEMBLE trial results.”
Dr. Erlander continued, “With regards to our ongoing Phase 2 trial in pancreatic cancer, we are pleased to announce encouraging initial results that show 4 out of 5 evaluable patients achieving disease control and remaining on-treatment as of the data cutoff date. Based in part on the strength of our results in mCRC and PDAC, as well as the unmet need and market opportunity in these indications, we will be focusing our resources on these programs and will not independently fund future clinical activities in prostate cancer. We will also continue to explore onvansertib’s potential in additional indications by leveraging investigator-initiated studies, which will allow us to operate with capital efficiency. Based on this approach and our current projections, we expect our current cash resources to fund company operations into 2025.”
mCRC Program: Topline data from ONSEMBLE, an open-label, randomized Phase 2 trial, expected in 2H 2024
Cardiff Oncology’s next trial in mCRC, ONSEMBLE, is designed to evaluate the safety and efficacy of onvansertib in combination with SoC FOLFIRI/bevacizumab in patients with second-line KRAS/NRAS-mutated mCRC. The trial is expected to enroll approximately 150 patients who will be randomized 1:1:1 to receive SoC alone, SoC plus 20 mg onvansertib, or SoC plus 30 mg onvansertib, with onvansertib administered on days 1-5 and 15-19 of 28-day treatment cycles. The primary endpoint of the trial is objective response rate (ORR). Progression-free survival (PFS) and duration of response (DoR) will be key secondary endpoints. Activation of the trial is expected in Q4 2022, with topline data expected in 2H 2024. If positive, Cardiff Oncology believes the trial results may position onvansertib for a possible accelerated approval opportunity in second-line KRAS/NRAS-mutated mCRC.
mCRC Program: Phase 1b/2 data presented at the ESMO Congress 2022 show durable responses to treatment
Data from the ongoing Phase 1b/2 trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC show patients experiencing durable responses to treatment, with a median duration of response of 11.7 months (95% confidence interval (CI): 8.9 – not reached). The ORR across all evaluable patients in the trial (n=48) is 35%, with responses observed across multiple KRAS variants. Median PFS across all evaluable patients in the trial is 9.3 months (95% CI: 7.6 – 13.5). Historical control trials of different drug combinations, including the SOC of
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FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and approximately 4.5 – 5.7 months, respectively1-4. These data were recently featured in a poster presentation at the European Society for Medical Oncology (ESMO) Congress 2022.
mCRC Program: Analysis from Phase 1b/2 trial shows improved ORR and mPFS in bevacizumab naïve patients
A new subgroup analysis from the ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC show an ORR of 69% and median PFS of 13.5 months in bevacizumab naïve patients (n=13). The ORR and mPFS for bevacizumab naïve patients were greater than those for the subgroup of trial participants with prior bevacizumab exposure (ORR=23%, mPFS=7.8 months, n=35), and for the population of all evaluable trial participants (ORR=35%, mPFS=9.3 months, n=48). This is well above historical control trials in mCRC which show an ORR of approximately 25% and a mPFS of approximately 6.9 months in bevacizumab naïve patients4-9. The observed increase in ORR in bevacizumab naïve patients was seen consistently across all patient characteristics and demographics in the trial. Based on these findings, the Company plans to stratify for prior bevacizumab exposure within the randomization of the ONSEMBLE trial and conduct preclinical studies to explore the apparent synergy between onvansertib and bevacizumab.
Metastatic PDAC Program: 1 partial response, 3 stable disease achieved in 5 evaluable patients
Preliminary data from 5 evaluable patients in an ongoing open-label Phase 2 trial of onvansertib in combination with nanoliposomal irinotecan and 5-FU in second-line metastatic PDAC show 1 patient achieving an initial partial response (PR) and 3 patients achieving stable disease (SD). The 4 patients achieving SD or a PR remain on study. The fifth evaluable patient discontinued the study due to progressive disease and an additional 3 patients are on-study and awaiting their first post-baseline scan as of the data cutoff date. Based on prior clinical studies, the historical ORR and median PFS for second-line PDAC patients are 7.7% and 3.1 months, respectively10,11. Additional data from the ongoing Phase 2 trial are expected in Q2 or Q3 2023.
Prostate Cancer Program
Following a strategic review of its clinical data in metastatic castrate-resistant prostate cancer (mCRPC), as well as the current and projected therapeutic landscape in this indication, the Company has decided it will not independently fund any future clinical activities in mCRPC.
Investigator-initiated Trials in Triple Negative Breast Cancer (TNBC) and Small Cell Lung Cancer (SCLC)
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 recommended phase 2 dose (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 Q4 2023 or Q1 2024. For more information, please visit NCT05383196.
A single-arm, two-stage, Phase 2 trial of onvansertib monotherapy in patients with relapsed SCLC is open for enrollment at the University of Pittsburgh Medical Center (UPMC). The trial is designed to enroll 15 patients in Stage 1, with the study proceeding to Stage 2 if 2 or more Stage 1 patients achieve an objective response. Stage 2 is designed to enroll an additional 20 patients. 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 Q2 or Q3 2023. For more information, please visit NCT05450965.
Webcast and Conference Call
Cardiff Oncology will host a webcast and conference call to discuss its clinical data, business updates, and corporate strategy today at 4:30 PM ET. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.
References
1.Giessen et al., Acta Oncologica 2015, 54, 187-193
2.Cremolini et al., Lancet Oncol 2020, 21, 497–507
3.Antoniotti et al., Correspondence Lancet Oncol. June 2020
4.Bennouna et al., Lancet Oncol. 2013, 14, 29–37
5.Hansen et al., Cancers 2021, 13, 1031
6.Tabernaro et al. Eur J Cancer, 2014, 50, 320-332
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7.Van Cutsem et al., J. Clin. Oncol. 2012, 30,3499–3506
8.Tabenaro et al, Lancet Oncol 2015, 16, 499–508
9.Beretta et al., Med Oncol 2013, 30:486
10.Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet 2016, 387:545-57
11.Waters AM, Der CJ. Cold Spring Harb Perspect Med 2018, 8(9)
About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SoC) therapeutics in clinical programs targeting indications such as KRAS/NRAS-mutated metastatic colorectal cancer (mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC). These programs and our broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SoC alone. For more information, please visit https://www.cardiffoncology.com.
Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; delays in initiation and completion of our clinical trials, our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; delays in initiation and completion of our clinical trials, our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
Cardiff Oncology Contact:
James Levine
Chief Financial Officer
858-952-7670
jlevine@cardiffoncology.com
Chief Financial Officer
858-952-7670
jlevine@cardiffoncology.com
Investor Contact:
Joyce Allaire
LifeSci Advisors
212-915-2569
jallaire@lifesciadvisors.com
Media Contact:
Amy Jobe, Ph.D.
LifeSci Communications
315-879-8192
ajobe@lifescicomms.com
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Clinical and Corporate Update SEPTEMBER 12, 2022
2 Forward-looking statements CERTAIN STATEMENTS IN THIS PRESENTATION ARE FORWARD-LOOKING within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern our expectations, strategy, plans or intentions. These forward-looking statements are based on our current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, our need for additional financing; our ability to continue as a going concern; clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; our clinical trials may encounter delays in initiation or enrollment that impact the cost and timing of the trial readout; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third-party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; regulatory, and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that any of our technology or products will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in our Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward- looking statements. Forward-looking statements included herein are made as of the date hereof, and we do not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
3 Many chemo agents damage a tumor cell’s ability to replicate DNA synthesis Initial cell growth Further cell growth Mitosis (cell division) S G2 G1 M Irinotecan 5-FU Taxanes
4 Cancers thrive because they prioritize DNA replication and cell division
5 PLK1 is a master regulator of genome integrity during cell replication DNA synthesis Initial cell growth Further cell growth Mitosis (cell division) S G2 G1 M
6 PLK1 is a master regulator of genome integrity during cell replication DNA synthesis Initial cell growth Further cell growth Mitosis (cell division) G2 G1 M S PLK1 plays multiple roles during cell cycle S-Phase Controls the repair of DNA damage G2/M Checkpoint M-Phase
7 PLK1 is a master regulator of genome integrity during cell replication DNA synthesis Initial cell growth Further cell growth Mitosis (cell division) G1 M S G2 PLK1 PLK1 plays multiple roles during cell cycle S-Phase Controls the repair of DNA damage G2/M Checkpoint Controls the checkpoint for DNA quality M-Phase
8 PLK1 is a master regulator of genome integrity during cell replication DNA synthesis Initial cell growth Further cell growth Mitosis (cell division) G2 G1 S M PLK1 plays multiple roles during cell cycle S-Phase Controls the repair of DNA damage G2/M Checkpoint Controls the checkpoint for DNA quality M-Phase Controls separation of chromosomes
9 PLK1 is a master regulator of genome integrity during cell replication onvansertib shuts down PLK1’s cell- preservation mechanisms, enhancing the efficacy of cell- damaging cancer therapies ONVANSERTIB INHIBITS PLK1
10 Onvansertib positions Cardiff Oncology to effectively target PLK1 • Small molecule • Oral dosing • 24-hour half-life ENZYME IC50 (µM) PLK1 0.002 PLK2 >10.000 PLK3 >10.000 CK2 0.400 FLT3 0.400 CDK1/CycB >10.000 42 other kinases and >140 in the Millipore panel >10.000 Exquisitely specific for PLK1 SPECIFICITYPROPERTIES
11 Two goals drive our near-term clinical development program 1 Validate prior mCRC data with a randomized trial 2 Demonstrate clinical POC in additional indications 2022 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 GOALS
12 Today we’ll see where we are, and where we’re going Accelerating our mCRC program Additional onvansertib programs Initial trial: phase 1b/2 Next trial
13 Today we’ll see where we are, and where we’re going Accelerating our mCRC program Additional onvansertib programs Pancreatic cancer (mPDAC) Triple negative breast cancer (TNBC) Small cell lung cancer (SCLC) Prostate cancer (mCRPC)
14 Initial trial: phase 1b/2 Next trial Accelerating our mCRC program Additional onvansertib programs
15 There are no targeted therapies available for KRAS/NRAS mutations 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 1st LINE 2nd LINENormal Mutated Standard Targeted FOLFIRI + bevacizumabFOLFOX + bevacizumab + EGFR inhibitor KRAS/NRAS mutatedNormal NONE Standard Targeted FOLFOX + bevacizumab FOLFIRI + bevacizumab NONE NONE Mutated mCRC is approx. half the mCRC population1
16 The prognosis for second-line mCRC patients is poor * Bennouna et al., Lancet Oncol 2013; 14: 29–37; Giessen et al., Acta Oncologica, 2015, 54: 187-193; Cremolini et al., Lancet Oncol 2020, 21: 497–507; Antoniotti et al., Correspondence Lancet Oncol June 2020. mCRC: metastatic colorectal cancer 2nd LINE FOLFIRI + bevacizumab NONE NONE HISTORICAL ORR 5% 11.4% 13% 2006 – 2008 2000 – 2013 2015 – 2017 *1st LINENormal Mutated Standard Targeted FOLFOX + bevacizumab + EGFR inhibitor Standard Targeted NONE FOLFOX + bevacizumab FOLFIRI + bevacizumab
17 Adding onvansertib to SoC could address the unmet need 2nd LINE FOLFIRI + bevacizumab NONE FOLFIRI + bevacizumab 1st LINENormal Mutated Standard Targeted FOLFOX + bevacizumab + EGFR inhibitor Standard Targeted FOLFOX + bevacizumab NONE ONVANSERTIB Onvansertib has the potential to fill this gap
18 G12C G12D G12V G13D G12S G12A Q61H G13CNRAS Normal Gaps in KRAS-mutated mCRC therapies leave a significant unmet need 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 3.8% Investigational therapies (Amgen; Mirati) address the G12C KRAS mutation only KRAS/NRAS Mutations in mCRC1
19 Gaps in KRAS-mutated mCRC therapies leave a significant unmet need 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 of patients with KRAS/NRAS mutations miss targeted therapy 93%G12C G12D G12V G13D G12S G12A Q61H G13CNRAS Normal KRAS/NRAS Mutations in mCRC1
20 Onvansertib is positioned to address gaps in KRAS-mutated mCRC MOA In KRAS-mutated mCRC, onversertib has two mechanisms of action 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 Synergy with 2nd-line SoC2 Synthetic lethality in KRAS mutants1G12C G12D G12V G13D G12S G12A Q61H G13CNRAS Normal KRAS/NRAS Mutations in mCRC1
21 2nd-Line SoC: FOLFIRI + bevacizumab 2nd-Line SoC: FOLFIRI + bevacizumab 28 DAY CYCLE Our Ph1/2b trial combined onvansertib with the current SoC 6 7 8 9 10 11 12 13 14 20 21 22 23 24 25 26 27 28 O N V A N S E R T I B O N V A N S E R T I B KRAS+ Unresectable 2nd line mCRC ENROLLMENT CRITERIA N=50 (48 evaluable) Can we get a signal that onvansertib complements and improves SoC? SINGLE ARM TRIAL
22 2nd-Line SoC: FOLFIRI + bevacizumab 2nd-Line SoC: FOLFIRI + bevacizumab 28 DAY CYCLE 6 7 8 9 10 11 12 13 14 20 21 22 23 24 25 26 27 28 O N V A N S E R T I B O N V A N S E R T I B KRAS+ Unresectable 2nd line mCRC ENROLLMENT CRITERIA N=50 (48 evaluable) Can we get a signal that onvansertib complements and improves SoC? SINGLE ARM TRIAL Our Ph1/2b trial assessed safety, efficacy and response biomarker EFFICACY ENDPOINTS Primary: Objective Response Rate (ORR) per RECIST v1.1 in patients who receive ≥1 cycle of treatment 1 Secondary: Progression-Free Survival (PFS) and Duration of Response (DoR)2 Exploratory: decrease in KRAS mutational burden and response to treatment 3 22
23 Patients achieved a strong, durable response with onvansertib + SoC * Waterfall plot and table reflect interim data as of July 25, 2022 from an ongoing trial and unlocked database Best Radiographic Response* – all doses (as of July 25, 2022) All Doses RP2D Objective Response Rate* (CR + PR) 34% (12/35)35% (17/48) Disease Control Rate (CR + PR + SD) 92% (44/48) Median Duration of Response 12.5 months11.7 months 94% (33/35) % c ha ng e in ta rg et le sio ns fr om b as el in e 30% tumor reduction Durability
24 We observe initial PRs up to eight months on treatment * Swimmer plot and table reflect interim data as of July 25, 2022 from an ongoing trial and unlocked database Evaluable Patients – all doses 48 Time of initial PR 8-week scan 16-week scan 24-week scan 32-week scan 8 3 5 1 Swimmer plot* – all doses (as of July 25, 2022) On Trial On Follow Up months
25 Patients achieved responses across several KRAS mutations Evaluable Patients – all doses 48 Time of initial PR 8-week scan 16-week scan 24-week scan 32-week scan 8 3 5 1 Swimmer plot* – all doses (as of July 25, 2022) months KRAS Variant CR+PR SD PD Total G12D 6 7 1 14 G12V 1 8 1 10 G13D 4 3 7 G12A 3 3 6 A146T 1 2 3 G12S 3 1 4 G12C 1 1 1 3 Q61H 1 1 Total 17 27 4 48 Onvansertib responses across KRAS mutations (as of July 25, 2022) Frequency of Common KRAS Mutations in mCRC1 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 G12C G12D G12V G13D G12S G12A Q61H G13C
26 2008 ‘13 ‘17 Objective Response Rate for mCRC trial exceeds SoC over time 42% RP2D Onvansertib+SoC ORR† over time 38% ALL DOSES Historical SoC* ORR 8 of 19 12 of 32 5% 11.4% 13% 20222021 Jan Apr Jul Oct Jan 35% RP2D34% ALL DOSES 12 of 35 17 of 4836% 5 of 14 ALL DOSES * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017: Cremolini et al., Lancet Oncol 2020, 21: 497–507; and Antoniotti et al., Correspondence Lancet Oncol June 2020. SoC: Standard-of-care † ORR data are interim data from an ongoing trial and unlocked database
27 Progression Free Survival for mCRC trial exceeds SoC over time * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017: Cremolini et al., Lancet Oncol 2020, 21: 497–507; and Antoniotti et al., Correspondence Lancet Oncol June 2020. SoC: Standard-of-care † mPFS is interim data from an ongoing trial and unlocked database. Progression free survival† – all doses (as of July 25, 2022) 9.3 Historical SoC* mPFS (mo) 2008 2013 2017 5.7 4.5 5.6 0.00 0.25 0.50 0.75 1.00 Pr ob ab ili ty o f S ur vi va l 0 5 10 15 20 Months Median PFS:
28 Progression Free Survival for mCRC trial exceeds SoC over time † Onvansertib mPFS are interim data from an ongoing trial and unlocked database * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017: Cremolini et al., Lancet Oncol 2020, 21: 497–507; and Antoniotti et al., Correspondence Lancet Oncol June 2020. SoC: Standard-of-care. mPFS: median progression free survival Onvansertib+SoC mPFS† 9.4 mo 20222021 Oct Jan 9.4 mo Apr Jul Oct 9.3 moHistorical SoC* mPFS (mo) 2008 2013 2017 5.7 4.5 5.6 RP2D 8.2 mo ALL DOSES
29 Onvansertib in combination with FOLFIRI-bev is well-tolerated * Data are interim as of July 25, 2022 from an ongoing trial and unlocked database. N: number of patients (total N=50); events shown occurred in ≥10% of patients; numbers indicate number of patients experiencing the event, (regardless of causality); each patient is only counted once and only for the highest grade of a given event. TEAEs: Treatment Emergent Adverse Events † Musculoskeletal pain, infection and hemorrhage are pooled terms No major/unexpected toxicities GRADE TEAEs* 1 2 3 4 All Neutropenia 1 13 15 6 35 Fatigue 15 15 3 0 33 Nausea 24 7 2 0 33 Diarrhea 15 7 2 0 24 Abdominal Pain 13 7 1 0 21 Mucositis 11 6 2 0 19 Alopecia 17 2 0 0 19 WBC Decrease 6 9 2 1 18 Platelet Count Decrease 10 4 1 0 15 Hypertension 2 8 5 0 15 • Of all TEAEs, only 11% (84/788) were G3/G4 • 7 patients had a total of 11 G4 adverse events: − Neutropenia (n=7); Decreased WBC (n=2); Neutropenic fever (n=1); Hyperphosphatemia (n=1) • Discontinuation of the 5-FU bolus + use of growth factors ameliorated the severity of neutropenia observed GRADE TEAEs* 1 2 3 4 All Anemia 9 4 1 0 14 Vomiting 9 3 1 0 13 Musculoskeletal Pain† 11 1 0 0 12 Infection† 3 4 4 0 11 Hemorrhage† 8 0 1 0 9 Headache 7 0 0 0 7 Neuropathy 5 2 0 0 7 GERD 7 0 0 0 7 ALT Increase 4 0 1 0 5
30 The trial’s patient demographics reflects 2nd line mCRC population * Data are interim as of July 25, 2022 from an ongoing trial and unlocked database, for the first 50 subjects. Number of Patients (N) Phase 1b, Dose Level 0 Onvansertib 12 mg/m2 Phase 1b, Dose Level +1 Onvansertib 15 mg/m2 Phase 1b, Dose Level +2 Onvansertib 18 mg/m2 Phase 2 RP2D Onvansertib 15 mg/m2 Total Patients All Doses Treated 6 6 6 32 50 Currently on treatment 0 0 0 3 3 Total Patients N=50 Median [range] or n (%) Age (years) 61 [35-83] Sex Male 28 (56%) Female 22 (44%) ECOG 0 33 (66%) 1 17 (34%) Primary tumor site Colon 27 (54%) Rectum 18 (36%) Other 5 (10%) Total Patients N=50 Median n (%) Liver metastasis None 13 (26%) Liver and other 27 (54%) Liver only 10 (20%) Number of metastatic organs 1 16 (32%) ≥2 34 (68%) Prior bevacizumab treatment5 Yes 35 (70%) No 15 (30%) Enrollment*
31 Anti-angiogenics, like bevacizumab, combine with 1st and 2nd line SoC Normal RAS Mutated 1st LINE FOLFOX + bevacizumab + EGFR inhibitor FOLFOX + bevacizumab 2nd LINE FOLFIRI + bevacizumab FOLFIRI + bevacizumab N=50 (48 evaluable) Do 2nd line patients naïve to bev show better efficacy than 2nd line patients with prior bev in 1st line? mCRC Ph1b/2 trial
32 1st line use of bev in prior trials has minimal impact on 2nd line efficacy 1. Hansen et al., Cancers 2021, 13, 1031; 2. Tabernaro et al. Eur J Cancer, 2014, 50, 320-332; 3. Bennouna et al., Lancet Oncol. 2013, 14, 29–37; 4. Van Cutsem et al., J. Clin. Oncol. 2012, 30,3499–3506; 5. Tabenaro et al, Lancet Oncol 2015; 16: 499–508; 6. Beretta et al., Med Oncol (2013) 30:486; 7. Moriwakij et al, Med Oncol (2012) 29:2842–2848. Normal RAS Mutated EFFICACY DATA FROM HISTORICAL TRIALS IN mCRC 2nd Line mOS (mo)1-2 13.9 12.5 No Yes 2nd Line mPFS (mo)1-2 6.9 6.7 No Yes 2nd LINE FOLFIRI + bevacizumab FOLFIRI + bevacizumab 2nd Line ORR3-6 25% 13% No Yes 5% BEV EXPOSURE IN 1ST LINE?
33 Ph 1b/2 trial bev naïve patients had unexpectedly high ORR and mPFS 1. Hansen et al., Cancers 2021, 13, 1031; 2. Tabernaro et al. Eur J Cancer, 2014, 50, 320-332; 3. Bennouna et al., Lancet Oncol. 2013, 14, 29–37; 4. Van Cutsem et al., J. Clin. Oncol. 2012, 30,3499–3506; 5. Tabenaro et al, Lancet Oncol 2015; 16: 499–508; 6. Beretta et al., Med Oncol (2013) 30:486. * Onvansertib ORR and mPFS are interim data as of July 25, 2022 from ongoing trial and unlocked database. Normal HISTORICAL CONTROLS VS ONVANSERTIB* Ph 1b/2 DATA 2nd Line mPFS (mo)1-2 6.9 6.7 No Yes 2nd LINE FOLFIRI + bevacizumab 2nd Line ORR3-6 25% 13% No Yes 5% 13.5 7.8 No Yes 69% 23% No Yes 13 FOLFIRI + bevacizumab + ONVANSERTIB BEV EXPOSURE IN 1ST LINE? RAS Mutated 35 3513
34 80% 80% 80% 75% 71% 70% 69% 67% 67% 67% 63% 60% 56% 50% 16% 27% 31% 14% 23% 26% 23% 25% 20% 23% 16% 23% 21% 25% RP2D No surgery Female No liver mets Only liver lesions Left or right colon tumor All patients Lesions (liver only) Had surgery Lesions (liver+) Male FOLFOX in the metastatic setting Metastatic diagnosis (M1) Left colon tumor N= ORR is consistently greater for bev naïve patients across characteristics * Onvansertib ORR and mPFS are interim data as of July 25, 2022 from an ongoing trial and unlocked database. 10 25 5 11 5 16 4 7 7 13 10 19 13 35 9 28 6 15 6 22 8 19 10 35 9 34 6 4 ORR (%) for Bevacizumab Naïve vs. Exposed Patients* No (naïve) Yes (exposed) Range of ORRs 14 – 31%50 – 80% No single patient characteristic explains observed ORR difference l p ts BEV EXPOSURE IN 1ST LINE?
35 The potential onvansertib bevacizumab synergy is a new opportunity * Onvansertib ORR and mPFS are interim data as of July 25, 2022 from an ongoing trial and unlocked database. 10 5 11 5 16 4 7 7 13 10 19 13 35 9 28 6 15 6 22 8 19 10 35 9 34 6 4 No (naïve) Yes (exposed) All Patients 23% ORR69% ORR How should we respond to this observation? ACTIONS OPPORTUNITY A. This is a statistical anomaly (small n)? B. This is due to onv / bev synergy? HYPOTHESES 1. Stratify for prior bev exposure within randomization of next mCRC trial 2. Explore apparent onv / bev synergy in pre-clinical studies 3. Analyze baseline ctDNA in Ph 1b/2 patients for genomic alterations in bev naïve vs bev exposed Conduct a 1st line exploratory mCRC trial of onvansertib + FOLFIRI + bev RP2D 80% ORR 16% ORR BEV EXPOSURE IN 1ST LINE?
36 Early KRAS MAF ctDNA decrease correlates w/ radiographic response Onvansertib KRAS MAF are interim data as of July 25, 2022 from an ongoing trial and unlocked database. 0 -50 -100 CR+PR SD PD % C ha ng e in K RA S M A F -96 -73 -63 * ** * KRAS MAF measured by droplet digital PCR (ddPCR) at baseline (day 1 of cycle 1, pre-dose) and on-treatment (day 1 of cycle 2 pre-dose). 1 PR and 2 SD patients had undetectable KRAS MAF at baseline. Predictive response biomarker • 45 of the 48 evaluable patients were evaluated for KRAS MAF changes • 87.5% (14/16) of CR/PR patients had ≥90% decrease in KRAS MAF after the 1st cycle • 32% (8/25) of SD patients and none of the PD patients (n=4) had such a decrease % KRAS Mutant Allelic Frequency (MAF)* decrease after one 28-day treatment cycle (Mean ±SD, as of July 25, 2022) KRAS MAF plot reflects interim data as of July 25, 2022 from an ongoing trial and unlocked database. mean mean mean -90
37 Early Changes in KRAS MAF predicts clinical response Onvansertib ORR and mPFS are interim data as of July 25, 2022 from an ongoing trial and unlocked database. ORR (%) 9% 2 of 23 KRAS NON-RESPONDERS 64% 14 of 22 KRAS RESPONDERS 12.6 mo mPFS (mo) 6.0 mo KRAS RESPONDERS KRAS NON-RESPONDERS P = 0.0190.00 0.25 0.50 0.75 1.00 Pr ob ab ili ty o f S ur vi va l 0 5 10 15 20 Months KRAS RESPONDERS KRAS NON-RESPONDERS 12.66.0
38 Initial trial: phase 1b/2 Next trial Accelerating our mCRC program Additional onvansertib programs
39 We believe that onvansertib complements and improves SoC * Bennouna et al., Lancet Oncol 2013; 14: 29–37; Giessen et al., Acta Oncologica, 2015, 54: 187-193; Cremolini et al., Lancet Oncol 2020, 21: 497–507; Antoniotti et al., Correspondence Lancet Oncol June 2020. mCRC: metastatic colorectal cancer Can we get a signal that onvansertib complements and improves SoC? Our Ph1b/2 Question: 2008 ‘13 ‘17 Historical SoC* ORR 5% 11.4% 13% 35% RP2D34% ALL DOSES 2022 Ph1b/2 ORR
40 We approach our next trial with four clear objectives DEMONSTRATE onvansertib’s contribution to SoC CONFIRM optimal dosing POSITION for possible accelerated approval opportunity OPERATE with capital efficiency
41 2nd-Line SoC: FOLFIRI + bevacizumab 2nd-Line SoC: FOLFIRI + bevacizumab 28 DAY CYCLE Our ONSEMBLE Ph2 trial is designed to demonstrate efficacy SoC (FOLFIRI + Bev) SoC + onvansertib (20mg) SoC + onvansertib (30mg) 6 7 8 9 10 11 12 13 14 20 21 22 23 24 25 26 27 28 O N V A N S E R T I B O N V A N S E R T I B KRAS+/NRAS+ Unresectable 2nd line mCRC N=150 1:1:1 R ENROLLMENT CRITERIA
42 Our ONSEMBLE Ph2 trial is designed to demonstrate efficacy ENDPOINTS Primary Key Secondary Other Secondary Objective Response Rate: CR + PR Progression-Free Survival Disease Control Rate: CR + PR + SD Duration of Response: DoR Overall Survival: OS Reduced MAF association with ORR, PFS, DCR, DoR, OS ENROLLMENT CRITERIA KRAS+/NRAS+ Unresectable 2nd line mCRC N=150 1:1:1 R
43 Our ONSEMBLE Ph2 trial will be statistically robust ENROLLMENT CRITERIA KRAS+/NRAS+ Unresectable 2nd line mCRC N=150 1:1:1 R • Randomized with control group exclusively the SoC • Examine two doses of onvansertib for safety/efficacy • Stratification within randomization for bev-naïve vs bev exposed • Efficient and cost effective DESIGN STATS • 80% minimum power to detect a meaningful difference in ORR • Optimal use of the significance level (alpha 0.045 for each treatment arm vs. control) • Ability to pool treatment arms for PFS
44 We are optimistic that randomized data will create substantial value 2022 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 mCRC randomized data readout Opportunity to create value • Rigorous demonstration of onvansertib’s role in increasing efficacy in mCRC vs. SoC alone • Position for possible accelerated approval opportunity in mCRC • Early identification of likely responders (MAF) • Strong indication that onvansertib has potential in other indications Trial activation
45 Pancreatic cancer (mPDAC) Prostate cancer (mCRPC) Triple negative breast cancer (TNBC) Small cell lung cancer (SCLC) Accelerating our mCRC program Additional onvansertib programs
46 Our mPDAC Ph2 trial combines onvansertib with standard-of-care 10 9 8 7 6 2nd-Line SoC: Nal-IRI + Leucovorin + 5-FU 14 DAY CYCLE 11 12 13 14 O N V A N S E R T I B Failed 1st Line Gemcitabine / Abraxane ENROLLMENT CRITERIA 43 patients planned Can we get a signal that onvansertib complements and improves SoC? SINGLE ARM TRIAL
47 The endpoints measure tumor response and duration of response 10 9 8 7 6 2nd-Line SoC: Nal-IRI + Leucovorin + 5-FU 14 DAY CYCLE 11 12 13 14 O N V A N S E R T I B Failed 1st Line Gemcitabine / Abraxane ENROLLMENT CRITERIA N=6/43 Here’s what we’re trying to gain from this trial SINGLE ARM TRIALEFFICACY ENDPOINTS Primary: Objective Response Rate (ORR) in patients who receive ≥28-days of treatment Secondary: Duration of Response (DOR) and mPFS, Overall Survival (OS) Exploratory: Identification of biomarkers related to sensitivity and resistance to treatment using patient-derived organoids, blood samples, and archival tissue biopsies 1 2 3 47
48 mPDAC trial is designed to demonstrate onvansertib’s efficacy vs SoC 10 9 8 7 6 2nd-Line SoC: Nal-IRI + Leucovorin + 5-FU 14 DAY CYCLE 11 12 13 14 O N V A N S E R T I B Failed 1st Line Gemcitabine / Abraxane ENROLLMENT CRITERIA N=6/43 Here’s what we’re trying to gain from this trial SINGLE ARM TRIAL HISTORICAL mPFS* 3.1 mo HISTORICAL RESPONSE RATE* 7.7% ORR PROOF OF CONCEPT CRITERIA 20% ≥6 mo ORR mPFS 48 * Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet 2016;387:545-57; Waters AM, Der CJ. Cold Spring Harb Perspect Med 2018;8(9).
49 Early data from our mPDAC trial data is encouraging * Swimmer and spider plots reflect interim data as of August 30, 2022 from an ongoing trial and unlocked database Swimmer plot* – as of August 30, 2022 0 2.5 5.0 7.5 Months Change in tumor size from baseline* 04-008 05-009 02-011 05-014 04-012 20 0 -20 -40 02-011 05-009 04-008 05-014 04-012 % C ha ng e in T ar ge t L es io ns 2 4 6 Months
50 Pancreatic cancer (mPDAC) Prostate cancer (mCRPC) Triple negative breast cancer (TNBC) Small cell lung cancer (SCLC) Accelerating our mCRC program Additional onvansertib programs
51 APRIL 2022 AACR data showed disease control increased with dose density Evaluated onvansertib + abiraterone / prednisone in mCRPC patients showing initial abiraterone resistance by rising PSA Disease control increased with onvansertib dose density • From 29% to 45% of patients achieving PSA stabilization, and • From 53% to 75% of patients with radiographic stable disease ctDNA analysis showed a correlation between the PI3K signaling pathway and sensitivity to onvansertib/abiraterone combination
52 We are not planning to fund any future mCRPC development activity The trial completed enrollment (n=72) and generated important clinical data: • Negligible toxicities attributed to onvansertib • Disease control increased with dose density Cardiff Oncology is not planning for any company- sponsored future steps in mCRPC FINDINGS PATH FORWARD
53 Pancreatic cancer (mPDAC) Prostate cancer (mCRPC) Triple negative breast cancer (TNBC) Small cell lung cancer (SCLC) Accelerating our mCRC program Additional onvansertib programs
54 Onvansertib + paclitaxel is superior to single agent therapy * SUM159 cells were implanted in the mammary fat pad of NOD-scid-IL2 receptor gamma null female mice, and treatments began as follows when tumor volume reached 40 mm3: vehicle, onvansertib oral (PO) twice per week (days 1-2), paclitaxel intraperitoneally (IP) weekly (day 1), or the combination. 1200 1000 Tu m or v ol um e (m m 3 ) 800 600 400 200 0 7 14 21 control (n=8) paclitaxel (10 mg/Kg IP q1 d8 n=8) onvansertib (120 mg/Kg PO d1,2 q8 n=9) Onvansertib + paclitaxel (n=10) In vivo efficacy of onvansertib in combination with paclitaxel Tp53-Mutant SUM159 xenografts* TRIAL RATIONALE The combination of onvansertib + paclitaxel showed significant synergy p<0.0001
55 Single arm trial Ph 1b: N=14−16 Ph 2: N=34 This is the first trial to explore onvansertib + paclitaxel combination Metastatic TNBC relapsed or progressed ENROLLMENT CRITERIA PRIMARY ENDPOINTS Phase 1b Safety, characterization of DLTs Determination of RP2D Paclitaxel 80 mg/m2 28 DAY CYCLE 22 23 24 25 26 27 28 O N V A N S E R T I B O N V A N S E R T I B D O S I N G Starting: 9 mg/m2 Escalation: 12 mg/m2 De-escalation: 6 mg/m2 Start: 9 mg/m2 Phase 2 ORR (RECIST 1.1)
56 This is the first trial to explore onvansertib + paclitaxel combination ENROLLMENT CRITERIA Paclitaxel 80 mg/m2 28 DAY CYCLE 22 23 24 25 26 27 28 O N V A N S E R T I B RP2D PRIMARY ENDPOINTS Phase 1b Safety, characterization of DLTs Determination of RP2D Phase 2 ORR (RECIST 1.1) SECONDARY ENDPOINT Phase 2 Progression-Free Survival (PFS) Single arm trial Ph 1b: N=14−16 Ph 2: N=34 Metastatic TNBC relapsed or progressed
57 Pancreatic cancer (mPDAC) Prostate cancer (mCRPC) Triple negative breast cancer (TNBC) Small cell lung cancer (SCLC) Accelerating our mCRC program Additional onvansertib programs
58 Onvansertib demonstrates single-agent activity in SCLC * Mice were implanted with SCLC PDX and treated with vehicle, cisplatin 3mg/kg IP weekly, or onvansertib oral 60mg/kg 10 ON / 4 OFF onvansertib cisplatin control 2000 1500 1000 500 0 Tu m or v ol um e (m m 3 ) 10 20 300 2000 1500 1000 500 0 0 10 20 30 40 Onvansertib monotherapy showed significant tumor growth inhibition against platinum-sensitive and -resistant models TRIAL RATIONALE Days on treatment Days on treatment CISPLATIN RESISTANT CISPLATIN SENSIVITVE onv. cis. con. In vivo efficacy of onvansertib monotherapy (SCLC xenografts)*
59 Single-arm trial Stage 1: N=15 Stage 2: N=20 This is the first trial to explore onvansertib monotherapy Relapsed who have received ≤ 2 prior therapies ENROLLMENT CRITERIA 15 16 17 18 19 20 21 O N V A N S E R T I B 21 DAY CYCLE onvansertib monotherapy 15 mg/m2 Phase 2 ORR (RECIST 1.1) PRIMARY ENDPOINT SECONDARY ENDPOINTS Phase 2 Progression-Free Survival (PFS) Overall Survival (OS)
60 Our pipeline opens many attractive opportunities for onvansertib Preclinical Ph1/2 Ph2/3 mPDAC TNBC SCLC Ovarian mCRC Onivyde/5-FU Paclitaxel None (monotherapy) PARP inhibitors FOLFIRI/bev Investigator-initiated trials Combination with: Enrolling Enrolling Status Enrolling Evaluating Activation mCRC FOLFIRI/bev Enrolling randomized single-arm Investigator
61 Targeting PLK1 opens doors to large patient populations 53 RETROS1 Annual eligible US patients (’000s)* ONVANSERTIB 15 SCLCTNBC 12 mPDAC 39 23 mCRC Targets with oncogenic alterations ROS1 RET KRAS G12C EGFR TRK Targets without oncogenic alterations PLK1 PARP CDK4/6 PD1/PDL1 VEGF *ROS1 estimated eligible patients presented in Turning Point Therapeutics’ corporate presentation May 2022 slide 6 (NSCLC disease incidence in the US of 140k of which 2% of patients harbor ROS1 translocation). RET estimated eligible patients presented in Loxo Oncology’s corporate presentation January 2018 disclosed on Form 8-K (Jan 8, 2018). mCRC estimated population includes 2nd line, KRAS- and NRAS-mutated cancers. mPDAC estimated population includes 2nd line PDAC patients. TNBC estimated population includes invasive, 2nd line TNBC patients. SCLC estimated population includes SCLC salvage patients. 2L K/N-mut 2L 2L invasive Salvage 30 20 10 0 40
62 We have multiple important catalysts over the next two years 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 mPDAC data readout SCLC data readout TNBC data readout 15 SCLCTNBC 12 mPDAC 39 23 mCRC mCRC randomized data readout 2L K/N-mut 2L 2L invasive Salvage
63 2025 Q1 Q2 At June 30, 2022, our financial position is robust * Financial information above is derived from our unaudited financials in Form 10Q filed on 8/4/22. June 30, 2022 cash and investments* $122.0M Net cash used in Operating Activities* (Rolling two-quarter period ending June 30, 2022) $16.9M 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 mCRC randomized data readout mPDAC data readout SCLC data readout TNBC data readout
64 Our clinical development program supports our key goals 1 Validate prior mCRC data with a randomized trial 2 Demonstrate clinical POC in additional indications GOALS 2025 Q1 Q2 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
65 Our clinical development program supports our key goals Phase 1b/2 single arm Phase 2 randomized Strong ORR + DoR + PFS MAF biomarker opportunity Efficient design Confirm dose; stratify bev1 Validate prior mCRC data with a randomized trial 2 Demonstrate clinical POC in additional indications GOALS Signal finding 2025 Q1 Q2 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 OUR STRATEGY
66 APPENDIX
67 Summary of onvansertib mCRC Ph1b/2 trial data over time * Data releases include certain follow up data and reflect interim data from an ongoing trial and unlocked database. ASCO GI Jan 2021 KOL Event Sept 2021 Investor Webcast Jan 2022 Investor Webcast Sept 2022 Data Cutoff Date Nov 1, 2020* July 2, 2021* Dec 3, 2021* July 25, 2022* All Doses All Doses RP2D All Doses RP2D All Doses RP2D Evaluable Patients 14 32 19 48 35 48 35 ORR (CR+PR) 36% (5) 38% (12) 42% (8) 35% (17) 34% (12) 35% (17) 34% (12) Confirmed CR/PRs 29% (4) 31% (10) 37% (7) 27% (13) 29% (10) 29% (14) 31% (11) Duration of Response 11.7 mos 12.5 mos mPFS 9.4 mos 9.4 mos 9.3 mos 8.2 mos Disease control rate (CR+PR+SD) 86% (12) 94% (30) 100% (19) 92% (44) 94% (33) 92% (44) 94% (33)