On February 24, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported recent company highlights and financial results from the fourth quarter and full year ended December 31, 2021 (Press release, Cardiff Oncology, FEB 24, 2022, View Source [SID1234608954]).

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"Our recent progress has provided additional clinical and external validation of onvansertib, including a Pfizer Breakthrough Growth Initiative collaboration," said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "As the number of evaluable patients in our lead program in KRAS-mutated metastatic colorectal cancer increased from 14 to 48 over the past year, we continued to see consistent objective response rates and median progression-free survival that substantially exceed those from historical control trials. We have also seen responses across multiple KRAS-mutation variants, which differentiates onvansertib from agents designed to target a specific KRAS mutation. We look forward to advancing our mCRC clinical program and moving into a pivotal trial."

Dr. Erlander added, "Alongside our lead program in mCRC, we continue our work to leverage onvansertib in other cancer indications. The addition of Tod Smeal, Ph.D., as our chief scientific officer was an important step towards this goal, and his experience developing targeted cancer therapies is already proving to be an invaluable asset. Looking ahead, we are eager to continue exploring synergistic combinations with onvansertib, which include DNA damaging agents, microtubule inhibitors and epigenetic factors, as we pursue additional indications."

Program highlights for the quarter ended December 31, 2021, and recent business updates include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced new data from Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab that continue to show robust objective response rate and progression-free survival

The data were presented on a webcast and conference call hosted by Cardiff Oncology, and a subset were featured in a poster presented by Heinz-Josef Lenz, M.D., FACP, principal investigator, USC Norris Comprehensive Cancer Center, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). Highlights from the webcast and conference call included:

Efficacy data in evaluable patients:

Among patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI/bevacizumab:
12 of 35 (34%) achieved an initial complete response (CR) or partial response (PR)
10 of 35 (29%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
Objective response rates of 5-13% observed in historical control trials in similar patient populations treated with various different drug combinations, including the standard-of-care chemotherapy of FOLFIRI with bevacizumab1-4
Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2)
17 of 48 (35%) achieved an initial CR or PR
13 of 48 (27%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
Median progression-free survival (mPFS), biomarker, and safety data:

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Responses (CRs or PRs) were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)
The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Corporate Highlights:

Received a $15 million equity investment from Pfizer as part of the Pfizer Breakthrough Growth Initiative

Pfizer purchased 2.4 million shares of Cardiff Oncology’s common stock at a price of $6.22 per share, which represented a 19% premium compared to the prior closing price. In connection with the equity investment, Adam Schayowitz, Ph.D., MBA, Vice President & Medicine Team Group Lead for Breast Cancer, Colorectal Cancer and Melanoma at Pfizer, will join Cardiff Oncology’s Scientific Advisory Board. Additionally, Cardiff Oncology agreed to grant Pfizer rights of first access to data from its development programs.

Strengthened management team with the appointments of Tod Smeal, Ph.D., as CSO and Charles Monahan, R.Ph., SVP, regulatory affairs

Dr. Smeal has over 20 years of industry experience developing targeted therapies and previously served as CSO of Cancer Biology at Eli Lilly and Company, and director of the Oncology Research Unit of Pfizer. Mr. Monahan is a registered pharmacist with over 20 years of regulatory experience developing drugs and biologics for oncology, infectious diseases, and ocular indications. Prior to joining Cardiff Oncology, he most recently served as the global head of regulatory affairs for Erytech PharmaSA.

Fourth Quarter and Full Year 2021 Financial Results:

As of December 31, 2021, Cardiff Oncology had approximately $141 million in cash, cash equivalents, and short-term investments.

Total operating expenses were approximately $9.6 million for the three months ended December 31, 2021, an increase of $3.0 million from $6.6 million for the same period in 2020. The increase in operating expenses was primarily due to ongoing and new onvansertib clinical development programs and preclinical activities, additional outside services, and recruiting fees.

Research and development expenses increased by approximately $2.6 million to $5.8 million for the three months ended December 31, 2021, from $3.2 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs and recruitment fees to fill critical research and development positions.

Selling, general and administrative expenses increased by approximately $0.4 million to $3.8 million for the three months ended December 31, 2021, from $3.4 million for the same period in 2020. The increase in selling, general and administrative expenses was primarily due to strategic valuation consulting related to our lead drug candidate onvansertib offset by lower legal expenses.

Net cash used in operating activities for the fourth quarter of 2021 was approximately $7.4 million, an increase of approximately $2.3 million from $5.1 million for the same period in 2020. This increase is primarily due to advancing clinical program activities and outside services and recruiting fees, and net changes in assets and liabilities.

Total operating expenses were approximately $29.2 million for the full year ended December 31, 2021, an increase of $9.8 million from $19.4 million for the full year 2020. The increase in operating expenses was primarily due to advancing existing and new onvansertib clinical development programs and preclinical activities, additional outside services, recruiting fees and stock compensation expense.

Research and development expenses increased by approximately $6.2 million to $17.4 million for the full year ended December 31, 2021, from $11.2 million for the full year 2020. The increase in research and development expenses was primarily due to advancing existing and new preclinical programs and collaborations.

Selling, general and administrative expenses increased by approximately $3.6 million to $11.8 million for the full year ended December 31, 2021, from $8.2 million for the full year 2020. The increase in selling, general and administrative expenses was primarily due to strategic valuation consulting, recruitment fees, and stock-based compensation expense.

Net cash used in operating activities for the full year 2021 was approximately $23.0 million, an increase of approximately $6.7 million from $16.3 million for the full year 2020.

On February 24, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported fourth quarter and full year 2021 financial results and corporate updates (Press release, Iovance Biotherapeutics, FEB 24, 2022, View Source [SID1234608970]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "Throughout 2021, we continued to build upon the strength of clinical data for Iovance TIL therapy in multiple solid tumor types and treatment settings. Highlights included long-term clinical data for one-time treatment with lifileucel in metastatic melanoma, the potential to increase response rates for TIL therapy in combination with pembrolizumab as an earlier treatment for melanoma, cervical and head and neck cancers, as well as an important proof-of-concept for Iovance TIL therapy in non-small cell lung cancer. We also advanced our genetically modified TIL pipeline and expect to initiate our first clinical study of a gene-edited TIL product candidate later this year. Our top priority remains our ongoing work to address feedback from the U.S. Food and Drug Administration (FDA) regarding the potency assays for lifileucel to support our planned biologics license application (BLA) submission in the first half of this year. We remain increasingly confident in the broad potential for TIL as the next class of paradigm-shifting therapy for cancer patients with significant unmet need."

Full Year 2021 Highlights and Recent Corporate Updates

Regulatory

Potency assays for lifileucel: Following FDA feedback regarding the potency assays for lifileucel, Iovance has continued ongoing work developing and validating its potency assays and has engaged in discussions with the FDA during the second half of 2021. The anticipated BLA submission for lifileucel continues to be planned for the first half of 2022. Resolution of the potency assay for lifileucel in melanoma is also a key step towards regulatory plans in other indications.
U.S. FDA Fast Track Designation for lifileucel in combination with pembrolizumab in metastatic melanoma: The FDA granted fast track designation for lifileucel in combination with pembrolizumab for the treatment of immune checkpoint inhibitor (ICI) naïve (frontline) metastatic melanoma based on the unmet medical need and potential advantages for this combination over available care.
Clinical

Iovance TIL therapy (lifileucel) in metastatic melanoma:
Lifileucel in late line (post-anti-PD-1) melanoma: Follow up data as assessed by investigators from Cohort 2 (n=66) in the C-144-01 study of lifileucel in advanced melanoma were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting. The overall response rate (ORR) was 36.4% (4.5% complete response rate and 31.8% partial response rate) and median duration of response (DOR) was not reached at 33.1 months of median study follow up. Iovance expects to report clinical data from the pivotal melanoma Cohort 4 as assessed by an independent review committee (IRC) in 2022 in connection with its BLA submission.
Lifileucel in combination with pembrolizumab in early line (anti-PD-1 naïve) melanoma (Cohort 1A in the IOV-COM-202 study): Initial clinical data were presented at ASCO (Free ASCO Whitepaper) 2021 and updated results were presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021. The updated ORR was 60% and the complete response rate was 30% at a median follow up of 11.5 months in Cohort 1A (n=10). Based on these results, Iovance intends to expand Cohort 1A and define a development strategy in early line melanoma in 2022.

Iovance TIL therapy (LN-145) in non-small cell lung cancer (NSCLC):

LN-145 monotherapy in metastatic NSCLC (mNSCLC): Results from Cohort 3B in the IOV-COM-202 study were highlighted at SITC (Free SITC Whitepaper) 2021. LN-145 showed a 21.4% ORR in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24). One complete response and one partial response were ongoing at 20.7 months and 3.0 months, respectively, at a median study follow up of 9.8 months. These results demonstrated activity for TIL therapy in heavily pretreated mNSCLC patients who received one or more prior systemic therapies, including anti-PD-1 therapy, and support the ongoing development strategy for LN-145 in second line mNSCLC patients in the IOV-LUN-202 study.
LN-145 in second-line mNSCLC: Enrollment is ongoing at more than 30 active clinical sites in the U.S., Canada and Europe for the IOV-LUN-202 study of LN-145 in patients with mNSCLC following a single line of approved systemic therapy. Iovance is engaged in discussions with the FDA about IOV-LUN-202 and intends to incorporate FDA feedback into the study design to support registration.

Lifileucel in cervical cancer: The C-145-04 study is investigating lifileucel for the treatment of metastatic cervical cancer patients following chemotherapy (Cohort 1), after chemotherapy and anti-PD-1/PD-L1 therapy (Cohort 2), and in combination with pembrolizumab in patients who have not had therapy for advanced disease (Cohort 3).

Lifileucel monotherapy in advanced cervical cancer: Iovance is engaged in regulatory discussions about a potential BLA for lifileucel in cervical cancer and intends to execute an updated registrational strategy based on FDA dialogue and feedback.
Lifileucel in combination with pembrolizumab in early line cervical cancer: Initial results from Cohort 3 (n=14) in the C-145-04 study were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated an ORR of 57.1% at a median follow up of 7.6 months.
Iovance TIL therapy combinations in additional solid tumor cancers: In Cohort 2A of the IOV-COM-202 study, Iovance is also investigating TIL therapy in combination with pembrolizumab in patients with head and neck squamous cell carcinoma (HNSCC) who are naïve to therapy with ICIs. Updated Cohort 2A data were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated a 38.9% ORR (n=18) at a median study follow up of 7.8 months. The IOV-COM-202 study is also investigating TIL combinations in patients with NSCLC including TIL therapy plus pembrolizumab (Cohort 3A) and TIL plus ipilimumab/nivolumab (Cohort 3C).
Next-Generation Genetically Modified TIL Products and Research Programs

Iovance expects to initiate its first clinical study of a genetically modified TIL product candidate in 2022. The lead program, designated IOV-4001, leverages the TALEN technology licensed from Cellectis S.A. to inactivate PD-1 expression in the TIL product.
Additional targets for genetic modification using the TALEN technology, including double knock-out programs, are in preclinical development.
Approaches to increase TIL potency using CD39/69 double negative TILs and gene knock-in targets are also in preclinical development.
Accepted abstracts at the upcoming Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR Tandem Meetings, April 23-26, 2022, describe TIL products manufactured from cryopreserved tumor samples shipped from Australia and a potential approach to optimize TIL memory-like phenotype and increase functionality during the manufacturing process.
Iovance continues to advance additional research and preclinical studies of next generation TIL therapies and related technologies, including a novel IL-2 analog (IOV-3001).
Manufacturing

Iovance Cell Therapy Center (iCTC): Commissioning activities were completed and clinical manufacturing of TIL product commenced at the iCTC, Iovance’s 136,000 square foot cell therapy manufacturing facility, in the third quarter of 2021. Commercial manufacturing remains on track to commence with a potential BLA approval.
Generation 3 (Gen 3) manufacturing: TIL product manufactured using a shorter 16-day third generation process (Gen 3) is being investigated in cohorts of metastatic melanoma patients in the IOV-COM-202 study as well as NSCLC patients in the IOV-LUN-202 study.
Corporate

Cash position of $602.1 million at December 31, 2021 is expected to be sufficient into 2024.
A strong organization of approximately 350 employees with an average of more than four years of cell therapy experience is in place to advance research, development, manufacturing, and commercial launch preparations.
Iovance continues to expand its intellectual property portfolio and currently owns more than 35 granted or allowed U.S. and international patents for TIL compositions and methods of treatment and manufacturing in a broad range of cancers. Iovance’s Gen 2 patent rights are expected to provide exclusivity into 2038. Iovance’s portfolio also includes patent applications and granted patents directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, tumor digest and fragment compositions and methods (including cryopreservation), and combinations of checkpoint inhibitors and TIL products.
Fourth Quarter and Full Year 2021 Financial Results

Iovance had $602.1 million in cash, cash equivalents, investments and restricted cash at December 31, 2021 compared to $635.0 million at December 31, 2020. The cash position is expected to be sufficient to fund current and planned operations into 2024.

Jean-Marc Bellemin, Chief Financial Officer, stated, "With late-stage clinical assets in our pipeline, as well as a strong balance sheet and investments focused on launch preparations, we are well positioned to execute our operating plan. We are confident in our prospects to deliver new treatment options to patients with great unmet need while enhancing shareholder value."

Net loss for the fourth quarter ended December 31, 2021, was $99.3 million, or $0.63 per share, compared to a net loss of $68.4 million, or $0.47 per share, for the fourth quarter ended December 31, 2020. Net loss for the full year period ended December 31, 2021, was $342.3 million, or $2.23 per share, compared to a net loss of $259.6 million, or $1.88 per share, for the full year period ended December 31, 2020.

Research and development expenses were $75.6 million for the fourth quarter ended December 31, 2021, an increase of $23.1 million compared to $52.5 million for the fourth quarter ended December 31, 2020. Research and development expenses were $259.0 million for the full year period ended December 31, 2021, an increase of $57.3 million compared to $201.7 million for the full year ended December 31, 2020.

The increase in research and development expenses in the fourth quarter 2021 over the prior year period was primarily attributable to an increase in costs associated with growth of the internal research and development team, including stock-based compensation expense, and increases in clinical trial costs and facility related costs associated with the iCTC. The increase in research and development expenses in the full year 2021 over the prior full year period was primarily attributable to growth of the internal research and development team and an increase in clinical trial costs and facility related costs associated with the iCTC.

General and administrative expenses were $23.8 million for the fourth quarter ended December 31, 2021, an increase of $7.7 million compared to $16.1 million for the fourth quarter ended December 31, 2020. General and administrative expenses were $83.7 million for the full year period ended December 31, 2021, an increase of $23.5 million compared to $60.2 million for the full year ended December 31, 2020.

The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the prior year periods were primarily attributable to an increase in costs associated with growth of the internal general and administrative team, including stock-based compensation expense, and an increase in intellectual property filing related costs.

Webcast and Conference Call

Iovance will host a conference call today at 4:30 p.m. ET to discuss the fourth quarter and full year 2021 financial results and corporate updates. The conference call dial-in numbers are 1-(844) 646-4465 (domestic) or 1-(615) 247-0257 (international) and the access code is 2877242. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.

On February 24, 2022 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, reported fourth quarter and full year 2021 financial results and recent business highlights (Press release, Sangamo Therapeutics, FEB 24, 2022, View Source [SID1234608986]).

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"In 2021, we continued to advance the development of genomic medicines for patients across multiple therapeutic areas using our innovative technologies," said Sandy Macrae, Chief Executive Officer of Sangamo. "We along with our partners presented compelling clinical data in our three lead programs and advanced development of preclinical product candidates using our second-generation technologies of CAR-Treg cell therapy for autoimmune diseases and engineered zinc finger transcription factors for neurological disorders. In addition, we completed and brought online our cell therapy manufacturing facilities in Brisbane and Valbonne and now have operational AAV and cell therapy facilities in-house. We believe this progress positions us well to generate long-term value for our shareholders."
Fourth Quarter Updates and Recent Business Highlights
Fabry disease – Updated preliminary Phase 1/2 data show continued safety, tolerability and elevated α-Gal A enzyme activity; Phase 3 planning initiated
•We presented updated preliminary clinical data from the Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, our wholly owned gene therapy product candidate for the treatment of Fabry disease at the 18th Annual WORLDSymposium earlier this month. As of the November 9, 2021 cutoff date:
◦The four patients in Cohorts 1 and 2 all exhibited above normal α-Gal A activity, ranging from 3-fold to 15-fold above mean normal at last measurement.
◦The two patients in Cohort 1 maintained elevated α-Gal A activity for one year and are now in the long-term follow-up study.
◦The first patient in Cohort 3 exhibited α-Gal A activity within mean normal range by week 2.
◦Lyso-Gb3 levels remained significantly reduced in the patient who exhibited the highest baseline levels of this biomarker.
◦The gene therapy candidate continued to be generally well tolerated in the five treated patients.
•The sixth patient in the STAAR study, who is the second patient in Cohort 3, was dosed after the cutoff date. We expect to provide updated data in the second half of 2022.
•Based on the Phase 1/2 data, we have initiated Phase 3 planning.
Sickle cell disease – Updated preliminary Phase 1/2 proof-of-concept safety, tolerability and efficacy results
•We presented updated preliminary proof-of-concept clinical data from the Phase 1/2 PRECIZN-1 study of SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development with Sanofi, at the 63rd American Society for Hematology Annual Meeting and Exposition (ASH 2021). As of the September 22, 2021 cutoff date:
◦No adverse events related to SAR445136 were reported.
◦All four treated patients experienced increases in total hemoglobin, fetal hemoglobin and percent F cells.
◦None of the patients required blood transfusions post engraftment.
•We expect that the next four patients treated in the study will be dosed with a product candidate manufactured using improved methods, which have been shown in internal experiments to increase long-term progenitor cells. We expect to complete dosing of these patients in the third quarter of this year.

•We and Sanofi are collaborating on an orderly transition of Sanofi’s rights and obligations under the program to Sangamo on June 28, 2022, while we explore options to advance the program, including seeking a potential new partner.
Hemophilia A – Updated Phase 1/2 results show sustained bleeding control in highest dose cohort through two years following giroctocogene fitelparvovec gene therapy
•With our collaborator Pfizer, we presented updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A, at ASH (Free ASH Whitepaper) 2021. As of the October 1, 2021 cutoff date:
◦At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort had resumed prophylaxis.
◦Giroctocogene fitelparvovec continued to be generally well-tolerated.
•Regarding the Phase 3 AFFINE trial of giroctocogene fitelparvovec, Pfizer has announced that it hopes to obtain agreements from health authorities to resume the AFFINE trial and to begin to reopen trial sites in the first half of 2022. This trial was previously paused when some of the patients treated in this trial experienced FVIII activity greater than 150% following treatment. Pfizer has announced that it currently is in the process of submitting a protocol amendment to health authorities in the countries where this trial is being conducted and preparing responses to the U.S. FDA clinical hold. Over 50% of the patients have been enrolled in the Phase 3 AFFINE trial.
Renal Transplant Rejection – First patient enrolled and expected to be dosed soon in Phase 1/2 study
•The first patient has been enrolled and is expected to be dosed soon in our Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous HLA-A2 CAR Treg cell therapy product candidate treating patients receiving an HLA-A2 mismatched kidney from a living donor. We expect the second patient in this study to be dosed by the middle of 2022. We continue to open study sites and screen patients.
Manufacturing – AAV and cell therapy cGMP manufacturing facilities fully operational
•We completed and brought online our in-house cell therapy manufacturing facilities in our Brisbane, California headquarters and in our Valbonne, France facilities in 2021, in addition to the in-house AAV manufacturing facilities we brought online in Brisbane in 2020.
Fourth Quarter and Full Year 2021 Financial Results
Consolidated net loss for the fourth quarter ended December 31, 2021 was $37.5 million, or $0.26 per share, compared to net loss of $40.7 million, or $0.29 per share, for the same period in 2020. For the year ended December 31, 2021, consolidated net loss was $178.3 million, or $1.23 per share, compared to consolidated net loss of $121.1 million, or $0.90 per share, for the year ended December 31, 2020.
Revenues
Revenues for the fourth quarter ended December 31, 2021 were $28.0 million, compared to $25.8 million for the same period in 2020.
The increase of $2.2 million in revenues was primarily due to increase in recognition of upfront license fees and research revenue of $3.7 million under our collaboration agreement with Novartis. The increase was partially offset by a decrease of $1.4 million in revenue related to the termination of our licensing agreement with Dow AgroSciences LLC in July 2021.
Revenues were $110.7 million in 2021, compared to $118.2 million in 2020. The decrease in revenues was primarily due to a decrease of $47.4 million of milestone fees and recognition of upfront license fees related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer resulting from the completion of our activities in 2020 and a decrease of $5.4 million from our collaboration agreements with Kite and Sanofi. These decreases were partially offset by higher revenues of $32.7 million and $14.4 million related to our collaboration agreements with Novartis and Biogen, respectively.
Total operating expenses on a GAAP basis for the fourth quarter ended December 31, 2021 were $67.9 million compared to $69.2 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the fourth quarter ended December 31, 2021 were $59.8 million, compared to $62.6 million for the same period in 2020.
The decrease in total operating expenses in the fourth quarter on a GAAP basis was primarily due to a reduction of research and development expenses by $5.2 million related to dissolution of the repayment obligation of a grant from California Institute for Regenerative Medicine associated with the discontinuation of the ST-400 program. This decrease was partially offset by an increase of $4.6 million in research and development expenses due to increased headcount to support the advancement of our clinical trials and our ongoing collaborations, and an increase in manufacturing and overhead costs as we ramped up our internal manufacturing operations.
Total operating expenses on a GAAP basis in 2021 were $294.0 million compared to $247.7 million in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, were $261.0 million and $222.0 million in 2021 and 2020, respectively.
The increase in total operating expenses in the full year on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our ongoing collaborations and an increase in manufacturing and overhead costs as we ramped up our internal manufacturing operations.
Cash, cash equivalents and marketable securities
Cash, cash equivalents and marketable securities as of December 31, 2021 were $464.7 million compared to $692.0 million as of December 31, 2020.
Initial Financial Guidance for 2022
On a GAAP basis, we expect total operating expenses in the range of approximately $320 million to $350 million in 2022, which includes non-cash stock-based compensation expense.
We expect non-GAAP total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $40 million, in the range of approximately $280 million to $310 million in 2022.
Conference Call
Sangamo will host a conference call today, February 24, 2022, at 4:30 p.m. Eastern Time, which will be open to the public. The call will also be webcast with live Q&A and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.
The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 2235808. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 2235808.

On February 24, 2022 Naveris, Inc., a leader in molecular diagnostics for viral cancers, reported the presentation of significant new data at the plenary session of the ASTRO 2022 Multidisciplinary Head and Neck Cancers Symposium supporting the clinical value of its flagship diagnostic test, NavDx (Press release, Naveris, FEB 24, 2022, View Source [SID1234609004]).

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In a real-world analysis of 1,076 patients treated for HPV-driven head and neck cancer in the surveillance setting across 124 U.S. medical sites, the NavDx blood test accurately identified 80 patients with recurrent cancers, showing an overall positive predictive value of 95%. A positive NavDx test, which measures tumor tissue modified viral HPV DNA ("TTMV-HPV DNA"), was the first indication of recurrence in 72% of these patients, previously considered to be disease-free, in which imaging and/or biopsy subsequent to the positive NavDx test confirmed the presence of recurrence.

"NavDx has fundamentally transformed, for the better, how patients treated for HPV-driven cancers are surveilled for the development of recurrence," said Naveris CEO Piyush Gupta, PhD. "This real-world study, the largest of its kind for HPV-related cancers, clearly shows how integration of Naveris’ innovative technology empowers physicians with actionable data in their management of patients."

"These data add to a growing and impactful literature on the power of circulating TTMV-HPV DNA to easily and accurately detect persistent or recurrent disease among patients with HPV-driven head and neck cancers," said Glenn Hanna, MD, a first author of the study and medical oncologist at the Dana-Farber Cancer Institute. "These data will no doubt inform future guidelines and may reshape surveillance practices. In addition, I expect we will be integrating TTMV-HPV DNA testing as a biomarker to guide treatment decisions for our patients."

The Multidisciplinary Head and Neck Cancers Symposium provides the most up-to-date information on multidisciplinary therapies, clinical research, treatment strategies, supportive care, scientific breakthroughs, and toxicity mitigation for the entire head and neck cancer community.

Presentation details:

Abstract Title: Detection of Occult Recurrence Using Circulating HPV Tumor DNA among Patients Treated for HPV-driven Oropharyngeal Squamous Cell Carcinoma
Presenter: Glenn Hanna, MD, Dana-Farber Cancer Institute
Scientific Session Title: K. Kian Ang, MD, PhD, FASTRO, Commemorative Plenary Session
Session Date: Thursday, February 24, 2022
Time: 1:30 p.m. – 3:00 p.m. (MST)/ 3:30 p.m.- 5:00 p.m. (EST)

Following the presentation, the data presented will be available on the Naveris website at View Source

On February 24, 2022 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies and infectious disease vaccines based on the Company’s proprietary Versamune and Infectimune T-cell activating technology, reported the presentation of preliminary safety data (Press release, PDS Biotechnology, FEB 24, 2022, View Source [SID1234609031]). The data are based on a total of 18 checkpoint inhibitor (CPI) naïve patients from the Company’s ongoing VERSATILE-002 Phase 2 study. The study is being conducted in collaboration with Merck (known as MSD outside the US and Canada) (NCT04260126). The data from the study will be presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

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The Phase 2 trial studies PDS0101 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of recurrent or metastatic HPV16-positive head and neck cancer. The trial is designed to treat both CPI naïve and refractory patients and will assess the primary efficacy endpoint, as well as partial response per RECIST 1.1. The Company previously announced that it had achieved its preliminary efficacy milestone in the CPI naive arm earlier this month.

Patients in the trial are treated with KEYTRUDA 200 mg intravenously every three weeks plus PDS0101 delivered subcutaneously with KEYTRUDA on cycles of 1-4 and again at cycle 12. An initial safety cohort was assessed during cycle 1 and 21 days following for dose-limiting toxicity, and thereafter for safety and tolerability of the combination.

Highlights from the PDS Biotech’s presentation at the 2022 Multidisciplinary Head and Neck Cancers Symposium regarding the preliminary results of the Phase 2 trial studying PDS0101 in combination with KEYTRUDA for the treatment of recurrent or metastatic HPV16-positive head and neck cancer include the absence of dose-limiting toxicities, drug discontinuation related to toxicity, or immune-related adverse events. Subjects received a median of 4 doses of PDS0101 (range 1-5) and a median of 6 doses of KEYTRUDA (range 1-13). In addition, no treatment-related grade 3 or higher toxicities were reported.

Preliminary safety data has shown that PDS0101 in combination with KEYTRUDA for the treatment of recurrent or metastatic HPV16-positive head and neck cancer is likely safe and well tolerated without evidence of enhanced or significant toxicity in the first 18 patients evaluated on the study. Accrual in this study has progressed to Stage 2 for the CPI naïve cohort and is ongoing in Stage 1 for the CPI refractory cohort. The full data set can be found under abstract number 157 at the virtual poster library, here.

Receipt of preliminary results are not necessarily indicative of the final-results of the Phase 2 trial studying PDS0101 in combination with KEYTRUDA for the treatment of recurrent or metastatic HPV16-positive head and neck cancer.

"We are encouraged by the preliminary safety data of PDS0101 in combination with KEYTRUDA for patients with recurrent or metastatic HPV16-positive head and neck cancer," commented Dr. Lauren V. Wood, Chief Medical Officer of PDS Biotech. "These data and the preliminary efficacy data continue to support the unique combination of safety and potency of our novel Versamune platform."

In addition to the ongoing VERSATILE-002 Phase 2 trial, PDS Biotech is conducting another Phase 2 clinical study in both second-and third-line treatment for multiple advanced HPV-associated cancers with the National Cancer Institute (NCI) (NCT04287868). A third Phase 2 clinical trial, IMMUNOCERV (NCT04580771), in first-line treatment of locally advanced cervical cancer is being performed with The University of Texas, MD Anderson Cancer Center. In addition, the Company recently announced a fourth Phase 2 trial with Mayo Clinic to study PDS0101 with and without KEYTRUDA prior to surgery in locally advanced HPV-associated oropharyngeal cancer (NCT05232851).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.