On November 3, 2022 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported financial results for the third quarter and first nine months of 2022 and provided a business update (Press release, Prothena, NOV 3, 2022, View Source [SID1234622980]).

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"Significant scientific and clinical progress has reinforced our understanding of the biology of Alzheimer’s disease and the impact that lowering amyloid plaque has on slowing cognitive and functional decline of people suffering from this devastating condition. This further strengthens our belief that PRX012, our next-generation subcutaneous anti-Aβ antibody, with a best-in-class profile, is positioned to lead a paradigm shift in the treatment of Alzheimer’s disease. Additionally, we look forward to presenting data on the observed survival benefit of birtamimab from the Phase 3 VITAL study in patients with Mayo Stage IV AL amyloidosis during an oral presentation at ASH (Free ASH Whitepaper) next month," said Gene Kinney, Ph.D., President and Chief Executive Officer of Prothena. "With our deep portfolio of investigational therapies and a strong cash position, Prothena remains well positioned to address the urgent needs of patients affected by neurodegenerative and rare peripheral amyloid diseases."

Third Quarter and Recent Business Highlights and Upcoming Milestones

Neurodegenerative Diseases Portfolio

Alzheimer’s Disease (AD)

PRX012, a potential best-in-class, next-generation subcutaneous treatment for AD, is an investigational monoclonal antibody targeting a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency

•Phase 1 multiple ascending dose (MAD) study initiation expected by year-end 2022
•Topline data from Phase 1 study expected in 2023

PRX005, a potential best-in-class treatment for AD, is an investigational antibody that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in diseases including AD, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), chronic traumatic

encephalopathy (CTE), and other tauopathies. PRX005 is part of the global neuroscience research and development collaboration with Bristol Myers Squibb

•Topline data from Phase 1 study expected by year-end 2022

PRX123, a potential first-in-class dual Aβ/tau vaccine treatment and prevention therapy for AD, is a dual-target vaccine targeting key epitopes within the Aβ and tau proteins to promote amyloid clearance and blockade of pathogenic tau

•IND filing expected in 2023

Parkinson’s Disease (PD)

Prasinezumab, a potential first-in-class treatment for PD, is a humanized monoclonal antibody designed to target key epitopes within the C-terminus of alpha-synuclein and is the focus of the worldwide collaboration with Roche

•Phase 2b PADOVA study in patients with early PD is being conducted by Roche (NCT04777331); topline data expected in 2024

Rare Peripheral Amyloid Diseases Portfolio

AL Amyloidosis

Birtamimab, a potential best-in-class amyloid depleter treatment for AL amyloidosis, is an investigational humanized monoclonal antibody designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid that causes organ dysfunction and failure

•Poster presented at the XVIII International Symposium on Amyloidosis (ISA) on September 5, 2022 titled: Birtamimab in Patients with Mayo Stage IV AL Amyloidosis: Rationale for Confirmatory AFFIRM-AL Phase 3 Study
•Abstract selected for oral presentation on Monday December 12, 2022, at 11:15 AM ET at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition titled: Survival Benefit of Birtamimab in Mayo Stage IV AL Amyloidosis in the Phase 3 VITAL Study Consistent After Adjustment for Baseline Variables
•Confirmatory Phase 3 AFFIRM-AL topline data expected in 2024

ATTR Amyloidosis

NNC6019 (previously PRX004), a potential first-in-class treatment for ATTR amyloidosis, is a humanized monoclonal antibody designed to deplete the pathogenic, non-native forms of the transthyretin (TTR) protein, that is being developed by Novo Nordisk for the treatment of ATTR cardiomyopathy

•Phase 2 trial of NNC6019 in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk (NCT05442047)

Upcoming Investor Conferences

Members of the senior management team will present and participate in investor meetings at the following upcoming investor conferences:

•Jefferies 2022 London Healthcare Conference on Wednesday, November 16, 2022, a fireside chat will be held at 12:00 PM ET
•Jefferies 5th Annual Denver Biopharma Summit on Wednesday, December 14, 2022, 1×1 investor meetings will be held

Third Quarter and First Nine Months of 2022 Financial Results
For the third quarter and first nine months of 2022, Prothena reported a net loss of $45.8 million and $123.3 million, respectively, as compared to a net income of $109.2 million and $100.2 million for the third quarter and first nine months of 2021, respectively. Net loss per share for the third quarter of 2022 and first nine months of 2022 was $0.97, and $2.63, respectively, as compared to net income per share on a diluted basis of $2.13 and $2.12 for the third quarter and first nine months of 2021, respectively.
Prothena reported total revenue of $1.5 million and $4.0 million for the third quarter and first nine months of 2022, respectively, primarily from collaboration revenue from BMS. As compared to total revenue of $139.2 million and $199.4 million for the third quarter and first nine months of 2021, respectively. Revenue for the third quarter of 2021 included collaboration revenue of $78.5 million from BMS for the option exercise and US license for PRX005 and $60.7 million from the sale of the clinical stage antibody NNC6019 (formerly PRX004) program and related rights to the Company’s ATTR amyloidosis business and pipeline to Novo Nordisk. In addition to third quarter 2021 revenue, the first nine months of 2021 revenue included collaboration revenue of $60 million in clinical milestone payment from Roche for dosing of first patient in the global Phase 2b PADOVA study for prasinezumab and license revenue from Roche.
Research and development (R&D) expenses totaled $39.9 million and $98.7 million for the third quarter and first nine months of 2022, respectively, as compared to $18.0 million and $60.2 million for the third quarter and first nine months of 2021, respectively. The increase in R&D expense for the third quarter and first nine months of 2022 compared to the same periods in the prior year was primarily due to higher manufacturing costs primarily related to the birtamimab, PRX012, PRX019, PRX123 and PRX005 programs, higher personnel related expenses, higher clinical trial expenses primarily related to the PRX012 and birtamimab programs, higher other R&D expense and higher consulting expenses. For the nine months ended September 30, 2022, the higher costs were offset in part by lower collaboration expenses related to the prasinezumab program with Roche as a result of the cost share opt-out exercised in May 2021 and lower manufacturing expenses related to the NNC6019 (formerly PRX004) program. R&D expenses included non-cash share-based compensation expense of $4.2 million and $11.3 million for the third quarter and first nine months of 2022, respectively, as compared to $2.5 million and $6.6 million for the third quarter and first nine months of 2021, respectively.
General and administrative (G&A) expenses totaled $12.0 million and $36.8 million for the third quarter and first nine months of 2022, respectively, as compared to $12.0 million and $34.1 million for the third quarter and first nine months of 2021, respectively. The increase in G&A expenses for the third quarter and first nine months of 2022 compared to the same periods in the prior year was primarily related to higher personnel related expenses. offset in part by lower legal expenses. G&A expenses included non-cash share-based compensation expense of $3.8 million and $12.6 million for the third quarter and first nine months of 2022, respectively, as compared to $3.6 million and $11.1 million for the third quarter and first nine months of 2021, respectively.
Total non-cash share-based compensation expense was $8.0 million and $23.9 million for the third quarter and first nine months of 2022, respectively, as compared to $6.1 million and $17.8 million for the third quarter and first nine months of 2021, respectively.

As of September 30, 2022, Prothena had $497.0 million in cash, cash equivalents and restricted cash, and no debt.
As of October 26, 2022, Prothena had approximately 48.4 million ordinary shares outstanding.

2022 Financial Guidance

The Company is updating its projected full year 2022 net cash burn from operating and investing activities, and expects it to be $108 to $120 million (versus prior guidance of $120 to $132 million) which includes an expected $40 million clinical milestone payment from Novo Nordisk, and expects to end the year with approximately $522 million in cash, cash equivalents, and restricted cash (midpoint) (versus prior guidance of $454 million) which is primarily driven by operating and financing activities. The updated estimated full year 2022 net cash burn from operating and investing activities is primarily driven by an updated estimated net loss of $121 to $137 million (versus prior guidance of $154 to $170 million), which includes an estimated $31 million of non-cash share-based compensation expense.

On November 3, 2022 Nektar Therapeutics (Nasdaq: NKTR) reported financial results for the third quarter ended September 30, 2022 (Press release, Nektar Therapeutics, NOV 3, 2022, View Source [SID1234622979]).

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Cash and investments in marketable securities on September 30, 2022, were approximately $546.4 million as compared to $628.2 million at the end of the second quarter of 2022. Our cash and marketable securities are expected to support our strategic development activities and operations through the middle of 2025.

"In the third quarter, we made progress advancing our biologics pipeline in oncology and immunology," said Howard W. Robin, President and CEO of Nektar. "With our partner, Eli Lilly, we presented positive proof-of-concept data for NKTR-358 in atopic dermatitis which demonstrate the potential for this first-in-class Treg stimulator to emerge as a differentiated therapy for patients with serious inflammatory conditions. In the first half of 2023, we expect Lilly to report topline data from the Phase 2 study of NKTR-358 in lupus as well as initiate a Phase 2 study in atopic dermatitis."

"In addition, we are also advancing NKTR-255 in large B-cell lymphoma, with plans to launch a comparative study in combination with approved autologous CD19 CAR-T therapies," continued Robin. "NKTR-255 targets the IL-15 pathway and we have conducted and published extensive preclinical studies showing that IL-15 can potentiate these approved cell therapies by expanding and extending the persistence of CAR-T cells. Finally, we are planning presentations at both SITC (Free SITC Whitepaper) and ASH (Free ASH Whitepaper) for both our preclinical and clinical programs that will showcase the strength of our science and lay the foundation for continued pipeline progress."

Summary of Financial Results

Revenue, which primarily includes non-cash royalty revenue, in the third quarter of 2022 was $23.6 million as compared to $24.9 million in the third quarter of 2021. Revenue for the first nine months of 2022 was $70.0 million as compared to $76.9 million in the first nine months of 2021. Revenue was lower compared to 2021 as a result of a decrease in non-cash royalty revenue.

Total operating costs and expenses in the third quarter of 2022 were $77.9 million as compared to $138.5 million in the third quarter of 2021. Total operating costs and expenses in the first nine months of 2022 were $393.7 million as compared to $410.1 million in the first nine months of 2021. Operating costs and expenses for the first nine months of 2022 include $124.3 million in restructuring, impairment and other costs of terminated program.

R&D expense in the third quarter of 2022 was $33.6 million as compared to $103.7 million for the third quarter of 2021. For the first nine months of 2022, R&D expense was $183.6 million as compared to $300.7 million in the first nine months of 2021. R&D expense decreased for both the third quarter and the first nine months of 2022 primarily due to the wind down of the bempegaldesleukin program.

G&A expense was $22.5 million in the third quarter of 2022 and $29.5 million in the third quarter of 2021. For the first nine months of 2022, G&A expense was $70.4 million as compared to $90.7 million in the first nine months of 2021. G&A expense decreased for both the third quarter and the first nine months of 2022 primarily due to the wind down of the bempegaldesleukin program.

Restructuring, impairment and other costs of terminated program was $16.8 million in the third quarter of 2022 and $124.3 million in the first nine months of 2022. The year-to-date amount includes $58.5 million in non-cash lease and equipment impairment charges, $29.8 million in employee severance expense and $28.9 million for clinical trial and related employee compensation costs for the wind down of the bempegaldesleukin program, as well as $7.1 million in other restructuring costs.

Net loss for the third quarter of 2022 was $59.0 million or $0.31 basic and diluted loss per share as compared to a net loss of $129.7 million or $0.70 basic and diluted loss per share in the third quarter of 2021. Net loss in the first nine months of 2022 was $308.5 million or $1.65 basic and diluted loss per share as compared to a net loss of $378.2 million or $2.07 basic and diluted loss per share in the first nine months of 2021.

Third Quarter 2022 and Recent Business Highlights:

In September 2022, Nektar presented data from two Phase 1b proof-of-concept studies of rezpegaldesleukin in patients with atopic dermatitis (AD) and plaque psoriasis at the 2022 European Academy of Dermatology and Venereology (EADV) Congress. Data from both studies showed rezpegaldesleukin’s ability to stimulate Tregs to target an immune system imbalance resulting in an improvement of disease activity in patients. Particularly in AD patients, dose-dependent improvements in key efficacy measures including EASI and vIGA-AD scores were observed for an additional 36 weeks following the 12-week treatment period.
In August 2022, Nektar announced the publication of preclinical data for NKTR-255 in Blood Advances, the open-access journal of the American Society of Hematology (ASH) (Free ASH Whitepaper). The data highlighted the effects of NKTR-255 on natural killer cell function and proliferation in multiple myeloma (MM), supporting the clinical development of NKTR-255 and further evaluation of the novel immunotherapeutic approach in MM, alone or in combination with monoclonal antibodies or potentially with other immunomodulatory drugs.
Nektar also announced upcoming presentations at the following scientific congresses:

The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting
November 8-12, 2022 (In person and virtual)

Poster presentation: "NKTR-288, a polymer-conjugated interferon gamma mutein for the treatment of solid tumors", Hamel, D., et al.
Poster presentation (Trials in Progress): "JAVELIN Bladder Medley: a phase 2 trial of avelumab in combination with other antitumor drugs as first-line maintenance therapy for advanced urothelial carcinoma", Hoffman-Censits, J., et al. (collaborator presentation with Merck KGaA)
2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting
December 10-13, 2022 (In person and virtual)

Poster presentation: "Safety, Tolerability, PK/PD and Preliminary Efficacy of NKTR-255, a Novel IL-15 Receptor Agonist, in Patients with Relapsed/Refractory Hematologic Malignancies", Patel K., et al.
Poster presentation (Trials in Progress): "A Phase 2/3, Randomized, Double Blind, Placebo-Controlled, Multicenter Study of NKTR-255 Vs Placebo Following CD-19 Directed CAR-T Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma", Perales M., et al.
Conference Call to Discuss Third Quarter 2022 Financial Results

Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time, November 3, 2022.

This press release and a live audio-only webcast of the conference call can be accessed through a link that is posted on the home page and Investors section of the Nektar website: View Source The web broadcast of the conference call will be available for replay through December 3, 2022.

To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call.

In the event that any non-GAAP financial measure is discussed on the conference call that is not described in this press release, or explained on the conference call, related information will be made available on the Investors section of the Nektar website as soon as practical after the conclusion of the conference call.

On November 3, 2022 Tyra Biosciences, Inc. (Nasdaq: TYRA), a precision oncology company focused on developing purpose-built therapies to overcome tumor resistance and improve outcomes for patients with cancer, reported financial results for the quarter ended September 30, 2022 and highlighted recent corporate progress (Press release, Tyra Biosciences, NOV 3, 2022, View Source [SID1234622978]).

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"We are proud of the steady advancement of our next-generation precision oncology pipeline designed to address the limitations of current and emerging product candidates, as highlighted by data presentations at ESMO (Free ESMO Whitepaper) and the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, which demonstrated the potency and selectivity of our lead FGFR programs, TYRA-300 and TYRA-200," said Todd Harris, CEO of TYRA. "Our team remains focused on enrolling and executing on our first clinical trial for TYRA-300, SURF301, submitting an IND for TYRA-200, and advancing our discovery pipeline of additional programs designed to overcome tumor resistance and improve outcomes for patients with cancer."

Recent Corporate Highlights

On November 2, 2022, TYRA announced that its Chief Financial Officer, Esther van den Boom, will be stepping down to transition into an advisory role at the end of 2022. Alan Fuhrman has been appointed as Chief Financial Officer effective January 1, 2023.

TYRA-300

As previously disclosed, in July 2022, the U.S. Food and Drug Administration (FDA) cleared TYRA to proceed with its Phase 1/2 SURF301 clinical study of TYRA-300, an FGFR3-selective inhibitor, in patients with metastatic urothelial carcinoma of the bladder and urinary tract. SURF301 is a two-part study designed to determine the optimal and maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D) of TYRA-300.
In September 2022, TYRA presented preclinical results that it believes showcase the enhanced anti-tumor activity and selectivity of TYRA-300 as compared to other agents in the class in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.
TYRA-200

In October 2022, TYRA presented preclinical results of TYRA-200, an FGFR1/2/3 inhibitor, with potency against FGFR2 fusions, molecular brake mutations and gatekeeper resistance at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium 2022. TYRA remains on track to submit an IND with the FDA for TYRA-200 by year-end 2022.
SNÅP Platform and Pipeline

During the third quarter, TYRA continued to progress its proprietary in-house discovery platform, SNÅP, and its pipeline of programs targeting achondroplasia and other FGFR3-related skeletal dysplasias, FGFR4-driven cancers, and RET (REarranged during Transfection kinase) driven cancers.
Third Quarter 2022 Financial Results

Third quarter 2022 net loss was $12.5 million compared to $6.6 million for the same period in 2021.
Third quarter 2022 research and development expenses were $10.9 million compared to $5.5 million for the same period in 2021.
Third quarter 2022 general and administrative expenses were $2.7 million compared to $1.2 million for the same period in 2021.
As of September 30, 2022, TYRA had cash and cash equivalents of $263.2 million.

On November 3, 2022 Adaptive Biotechnologies Corporation ("Adaptive Biotechnologies") (Nasdaq: ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, reported financial results for the quarter ended September 30, 2022 (Press release, Adaptive Biotechnologies, NOV 3, 2022, View Source [SID1234622977]).

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"We continue to deliver solid growth in both of our business areas quarter over quarter, and are confident in our long-term outlook," said Chad Robins, chief executive officer and co-founder of Adaptive Biotechnologies. "With a bolstered cash position from our recent financing, we are focused on driving growth and innovation across our businesses with a clear path to profitability."

Recent Highlights

•Revenue of $47.8 million for the third quarter 2022, representing a 21% increase from the third quarter 2021.
•clonoSEQ test volume in the third quarter 2022 grew 52% versus the third quarter of prior year.
•Signed partnership with Epic to integrate the clonoSEQ Assay into Epic’s comprehensive electronic medical record (EMR) system.
•Immune Medicine business grew 18% in the third quarter 2022 versus the third quarter 2021, driven by drug discovery and pharma services.
•Signed non-dilutive royalty financing agreement with OrbiMed for up to $250 million.
•Provided long-term guidance including revenue CAGR from 2022-2027 at 20%-30%, positive adjusted EBITDA in 2025 and cash flow breakeven in 2026.
Third Quarter 2022 Financial Results

Revenue was $47.8 million for the quarter ended September 30, 2022, representing a 21% increase from the third quarter in the prior year. Immune Medicine revenue was $27.9 million for the quarter, representing an 18% increase from the third quarter in the prior year. MRD revenue was $20.0 million for the quarter, representing a 26% increase from the third quarter in the prior year.

Operating expenses were $93.3 million for the third quarter of 2022, compared to $95.8 million in the third quarter of the prior year, representing a decrease of 3%. Interest expense from our revenue interest purchase agreement entered into during the third quarter of 2022 was $0.7 million.

Net loss was $45.3 million for the third quarter of 2022, compared to $56.0 million for the same period in 2021.

Adjusted EBITDA (non-GAAP) was a loss of $25.9 million for the third quarter of 2022, compared to a loss of $41.1 million for the third quarter of the prior year.

Cash, cash equivalents and marketable securities was $527.8 million as of September 30, 2022.

2022 Financial Guidance

Adaptive Biotechnologies narrows full year 2022 revenue to be in the range of $185 million to $190 million compared to the previous expectation of $185 million to $195 million.

We now expect full year 2022 operating expenses to be below $400 million compared to the previous expectation of between $410 million and $415 million.

Webcast and Conference Call Information

Adaptive Biotechnologies will host a conference call to discuss its third quarter 2022 financial results after market close on Thursday, November 3, 2022 at 4:30 PM Eastern Time. The conference call can be accessed at View Source The webcast will be archived and available for replay at least 90 days after the event.

On November 3, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results and recent highlights for the third quarter ended September 30, 2022 (Press release, Cardiff Oncology, NOV 3, 2022, View Source [SID1234622976]).

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"We recently announced Phase 1b/2 data that demonstrate onvansertib’s ability to generate durable responses in KRAS-mutated mCRC patients, with various underlying mutations, when combined with standard-of-care FOLFIRI/bevacizumab. In addition, we observed an increase in objective response rate and progression-free survival in the bevacizumab-naïve subgroup of patients, providing key learnings to maximize ovansertib’s therapeutic and commercial potential," said Mark Erlander, PhD, chief executive officer of Cardiff Oncology. "In the fourth quarter we plan to activate ONSEMBLE, a randomized Phase 2 trial in our lead KRAS/NRAS-mutated mCRC program. This trial is designed to corroborate the robust signal of efficacy provided by the Phase 1b/2 results and position onvansertib for a possible accelerated approval opportunity by demonstrating its contribution over standard-of-care alone."

Dr. Erlander continued, "With a clear strategic focus and projected cash runway into 2025, we believe we are well positioned to generate value from each of our programs in the coming months and years."

Recent highlights for the quarter ended September 30, 2022 include:

KRAS/NRAS-mutated mCRC Program:

ONSEMBLE, a Phase 2, open-label, randomized trial for second line treatment of KRAS/NRAS-mutated mCRC, on track for activation in Q4 2022

The Company designed the ONSEMBLE trial to corroborate the robust efficacy signal observed in the Phase 1b/2 trial of onvansertib plus standard-of-care (SoC) FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC, demonstrate onvansertib’s contribution above SoC alone and confirm the optimal dose. ONSEMBLE 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, and topline data are expected in 2H 2024.

Phase 1b/2 mCRC data show durable response to treatment across multiple KRAS-mutation variants, as well as an objective response rate and median progression-free survival that substantially exceed those observed in historical control trials

Data from the Phase 1b/2 trial of onvansertib plus FOLFIRI/bevacizumab in second line KRAS-mutated mCRC were presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 and on a company webcast on September 12, 2022. Key data and conclusions featured in these presentations include:

•Objective response rate (ORR) across all evaluable patients was 35% (n=48) as compared to an ORR of 5-13% observed historically1-4, and the median duration of response (mDoR) across all evaluable patients was 11.7 months
•Median progression-free survival (mPFS) was 9.3 months across all evaluable patients, as compared to mPFS of ~4.5 – 5.7 months observed historically in combination trials that included the standard-of-care FOLFIRI with bevacizumab1-4

Subgroup analysis from Phase 1b/2 mCRC trial shows improved ORR and mPFS in bevacizumab naïve patients

A recently reported subgroup analysis from the ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second line KRAS-mutated mCRC showed an ORR of 69% and mPFS of 13.5 months in bevacizumab naïve patients (n=13). These data compare favorably to 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 in the Phase 1b/2 trial was seen consistently across all patient characteristics and demographics. 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.

Data presented at the ESMO (Free ESMO Whitepaper) conference suggest combining onvansertib with irinotecan (a component of FOLFIRI) overcomes irinotecan-resistance in RAS-mutated mCRC

Findings from Cardiff Oncology’s Expanded Access Program (EAP) of onvansertib in KRAS-mutated mCRC as well as preclinical data from patient-derived xenograft (PDX) models of irinotecan-resistant, RAS-mutated mCRC were featured in a poster at the ESMO (Free ESMO Whitepaper) Congress 2022. Highlights from the presentation include:

•EAP patients with prior irinotecan treatment (43 of 51) showed clinical benefit following treatment
•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

Collectively, these results support the observed mDoR in Cardiff Oncology’s ongoing Phase 1b/2 trial in KRAS-mutated mCRC and suggest onvansertib may combine with irinotecan to overcome mechanisms driving intrinsic and refractory resistance.

Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) Program:

Preliminary data provide early signal of efficacy and compare favorably to historical control trials

Preliminary data from five 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 showed one patient achieving an initial partial response (PR) and three patients achieving stable disease (SD). Based on prior clinical studies, the historical ORR and mPFS for second-line mPDAC patients are 7.7% and 3.1 months, respectively10,11. All four patients achieving a PR or SD remained on study without disease progression as of the data cut-off date and all have shown tumor shrinkage from baseline. Additional data from the ongoing Phase 2 trial are expected in mid-2023.

Investigator-initiated Trials

Trials in triple negative breast cancer (TNBC) and small cell lung cancer (SCLC) enrolled first patients

A single-arm, Phase 1b/2 trial of onvansertib in combination with paclitaxel in patients with unresectable locally advanced or metastatic TNBC recently enrolled its first patient at Dana Farber Cancer Institute (DFCI). Preliminary data from the trial are expected in late 2023 or early 2024. For more information, please visit NCT05383196.

A single-arm, two-stage, Phase 2 trial of onvansertib monotherapy in patients with relapsed SCLC recently enrolled its first patient at the University of Pittsburgh Medical Center (UPMC). Preliminary data from the trial are expected in mid-2023. For more information, please visit NCT05450965.

Third Quarter 2022 Financial Results:

Liquidity, cash burn and cash runway

As of September 30, 2022, Cardiff Oncology had approximately $114 million in cash, cash equivalents, and short-term investments.

Net cash used in operating activities for the third quarter of 2022 was approximately $7.5 million, an increase of approximately $2.0 million from $5.5 million for the same period in 2021. Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into 2025.
Operating Expenses

The overall increase in research and development expenses was primarily related to chemistry, manufacturing, and controls ("CMC"); and clinical pharmacology studies to support the development of our lead drug candidate, onvansertib. Salaries and staff costs increased primarily due to additional hires in senior management and our clinical operations team.

The overall increase in selling, general and administrative expense was primarily due to higher salaries costs from merit increases and additional new hires. An increase in D&O insurance costs also contributed to higher selling, general and administrative expenses in the current period, offset by a reduction in recruiting fees from the prior period.