On February 24, 2022 Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) reported that it will report its financial results for the fourth quarter of 2021, on Thursday, March 3, 2022, before the U.S. financial markets open Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) reported that it will report its financial results for the fourth quarter of 2021, on Thursday, March 3, 2022, before the U.S. financial markets open. The Company will host a conference call and webcast at 8:30 a.m. ET to discuss its fourth quarter 2021 financial results and provide a business update. Individuals interested in participating in the call should dial (855) 354-1855 (U.S. and Canada) or (484) 365-2865 (International).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A live webcast of the conference call may be accessed in the Investors section of the Company’s website at www.concertpharma.com. A replay of the webcast will be available on Concert’s website for three months.. The Company will host a conference call and webcast at 8:30 a.m. ET to discuss its fourth quarter 2021 financial results and provide a business update. Individuals interested in participating in the call should dial (855) 354-1855 (U.S. and Canada) or (484) 365-2865 (International).

A live webcast of the conference call may be accessed in the Investors section of the Company’s website at www.concertpharma.com. A replay of the webcast will be available on Concert’s website for three months.

On February 24, 2022 Compugen Ltd. (Nasdaq: CGEN, "Compugen", the "Company"), a clinical-stage cancer immunotherapy company and leader in predictive target discovery, reported financial results for the fourth quarter ended December 31, 2021, and full year 2021 and provided an update on recent Company highlights (Press release, Compugen, FEB 24, 2022, View Source [SID1234608957]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Compugen made excellent progress in 2021. As the leader in the DNAM-1 axis we believe that blocking its complementary pathways has the potential to be a game changer in treating inflamed as well as less inflamed tumors, in patients who do not respond to available therapies. I am particularly excited about the translational data we presented across all the regimens with the most potent immune activation in the triple blockade of PVRIG, TIGIT and PD-1, which complements the early signals of anti-tumor activity we reported in our studies. With COM902, we were the first to present early signals of monotherapy anti-tumor activity with an IgG4 anti-TIGIT antibody, with low Fc-effector function. COM902 also avoided depletion of CD8+ T cells, the most effective anti-cancer immune subset, supporting our strategy to develop an antibody with low Fc effector function said," Anat Cohen-Dayag, Ph.D., President and CEO of Compugen. "In 2021 we also presented additional research supporting the differentiation of PVRIG from other immune checkpoints, enhancing our belief that PVRIG may be the missing piece when current immunotherapies have failed, by potentially generating new waves of T cells to infiltrate the tumor microenvironment. I am excited that the totality of results we have presented to date support our DNAM-1 axis hypothesis and set the stage for the next steps for the Company’s clinical program."

Dr. Cohen-Dayag further commented, "I am also pleased that we expanded our collaboration with Bristol Myers Squibb with a $20 million strategic investment and I am happy to see AstraZeneca progressing its TIGIT/PD-1 bispecific, which is derived from our COM902 into the clinic."

Dr. Cohen-Dayag continued, "Looking ahead, this year and next year we will focus on completing clinical study enrollment and delivering meaningful clinical and translational results from the expansion cohorts in our three ongoing combination studies with our two proprietary programs, COM701 and COM902. We expect to report data from fully enrolled cohorts in each of our studies as available starting with the COM701/nivolumab study CRC (MSS) cohort in Q4 2022, and complete enrollment in all cohorts by the end of 2023. The data from these studies will guide our regulatory strategy on a cohort-by-cohort basis."

2022-2023 Expected Milestones:
•
Advancing the enrollment of Phase 1 and Phase 1/2 dose expansion studies to evaluate anti-PVRIG and/or anti-TIGIT antibodies in combination with a PD-1 inhibitor:

o
COM701/PVRIG plus nivolumab

o
COM701/PVRIG plus COM902/TIGIT

o
COM701/PVRIG plus nivolumab and Bristol Myers Squibb’s investigational anti-TIGIT antibody, BMS-986207
•
Reporting data from fully enrolled cohorts
•
Announcing initial clinical data from the Phase 1 and Phase 1/2 programs starting with COM701/nivolumab study CRC/MSS cohort in Q4 2022
•
Completing enrollment of all ongoing studies by end of 2023

Phase 1/Phase 1/2 Dose Expansion Combination Program
Clinical Study
Number of cohorts
Tumor types
Patients per cohort
COM701+ nivolumab
4
Ovarian, Endometrial, Breast, CRC/MSS
20
COM701+ nivolumab + BMS986207
4
Ovarian, Endometrial, HNSCC, PVRL2+ patients
20
COM701 +COM902
3
HNSCC, NSCLC, CRC/MSS
20

2021 Corporate Highlights
•
Completed enrollment as planned and presented data from our Phase 1 studies at major medical meetings

o
ASCO 2021

◾
COM701 monotherapy dose escalation and expansion studies

◾
COM701 + nivolumab dose escalation study

o
SITC 2021

◾
COM902 monotherapy dose escalation

◾
COM701+ nivolumab + BMS986207 dose escalation
•
COM701 as mono, dual, and triple therapy showed early signals of anti-tumor activity with immune activation and a favorable safety profile
•
COM902 showed early signals of anti-tumor activity, was well tolerated and translational data support choice of an IgG4 anti-TIGIT antibody with less effector function than IgG1

•
Initiated enrollment in the Phase 1, Phase 1/2 dose expansion programs (see table above)
•
Expanded the clinical research collaboration agreement with Bristol Myers Squibb with an equity investment of $20 million
•
Received $6 million milestone payment triggered by first patient initiation in AstraZeneca’s Phase 1/2 study of a TIGIT/PD-1 bispecific monoclonal antibody, AZD2939, derived from COM902
•
Expanded research collaboration with Johns Hopkins University for a novel myeloid target discovered by Compugen
•
Published review on biology and potential therapeutic relevance of DNAM-1 axis in cancer immunotherapy in Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper)
•
Published preclinical data on the potential of COM902 to enhance anti-tumor immune responses, in Cancer Immunology Immunotherapy
•
Presented research supporting the differentiation of PVRIG from other immune checkpoint inhibitors at the SITC (Free SITC Whitepaper) 2021 Targets for Cancer Immunotherapy seminar series in June, the SITC (Free SITC Whitepaper) in November and translational data from patient biopsies demonstrating immune activation in the TME after treatment with COM701, at the TIGIT Therapies Digital Summit in December

Fourth Quarter and Full Year 2021 Financial Highlights
Cash: As of December 31, 2021, cash, cash related accounts, short-term and long-term bank deposits totaled to approximately $118 million, compared with approximately $124 million as of December 31, 2020. The Company expects its existing cash and cash equivalents and short-term bank deposits, to be sufficient to fund our current level of operations into 2024.

Revenues: Compugen reported no revenue for the fourth quarter of 2021 and a total of $6 million for the year ended December 31, 2021, compared with $2.0 million for each of the comparable periods in 2020. 2021 revenues are related to the milestone payment from AstraZeneca for dosing the first patient in AstraZeneca’s Phase 1/2 study of a TIGIT bispecific monoclonal antibody, derived from COM902.

Cost of revenues: 2021 expenses of approximately $0.7 million are attributed to royalty and milestone payments.

R&D Expenses: Expenses for the fourth quarter and year ended December 31, 2021 were approximately $5.8 million, and approximately $28.7 million, respectively, compared with approximately $8.1 million and approximately $22.8 million for the comparable periods in 2020. The increase in the annual periods is attributed mainly to higher expenses associated with our various clinical studies, manufacturing and related costs, and headcount as the U.S. based clinical team continues to grow to support the expansion of our studies. The decrease in the quarterly period is due to a decrease in manufacturing and related costs.

G&A Expenses: Expenses for the fourth quarter and year ended December 31, 2021 were approximately $2.7 million and approximately $10.9 million, respectively, compared with approximately $2.7 million and approximately $9.8 million for the comparable periods in 2020. The increase in the annual period is mainly due to increased corporate-related expenses.

Net Income/Loss: Net loss for the fourth quarter of 2021 was approximately $8.6 million, or $0.10 per basic and diluted share, compared with a net loss of approximately $8.6 million, or $0.10 per basic and diluted share in the comparable period of 2020. Net loss for the year ended December 31, 2021 was approximately $34.2 million, or $0.41 per basic and diluted share, compared with net loss of approximately $29.7 million, or $0.37 per basic and diluted share in the comparable period of 2020.

Full financial tables are included below.

Conference Call and Webcast Information
The Company will hold a conference call today, February 24, 2022, at 8:30 AM ET to review its fourth quarter and full year 2021 results. To access the conference call by telephone, please dial 1-866-744-5399 from the United States, or +972-3-918-0610 internationally. The call will also be available via live webcast through Compugen’s website, located at the following link. Following the live audio webcast, a replay will be available on the Company’s website.

On February 24, 2022 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it will report its financial results for the fourth quarter and year-end 2021 ending December 31, 2021, on Thursday, March 3, 2022, after the close of the US market (Press release, Cellectis, FEB 24, 2022, View Source [SID1234608955]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The announcement will be followed by a conference call and live audio webcast on Friday, March 4, 2022, at 8:00 AM EDT / 2:00 PM CET, prior to the open of the US market. The call will include the Company’s fourth quarter results, year-end results, and an update on business activities. Details for the call are as follows:

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported business highlights and financial results for the year ended December 31, 2021 (Press release, C4 Therapeutics, FEB 24, 2022, View Source [SID1234608953]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The progress achieved across our organization in 2021, a year in which we dosed the first patient with our lead program while advancing additional candidates towards the clinic, was instrumental in laying a foundation for C4T’s vision to transform patient care through targeted protein degradation," said Andrew Hirsch, chief executive officer of C4 Therapeutics. "Supported by the strength of our balance sheet and the productivity of our TORPEDO platform, we are well-positioned to advance our pipeline in 2022. We look forward to the AACR (Free AACR Whitepaper) Annual Meeting, where we will share clinical data from Cohort A in our Phase 1/2 trial evaluating CFT7455 in hematologic malignancies, as well as pre-clinical data from three programs that demonstrate differentiation and versatility of our TORPEDO platform. Throughout 2022, we expect to drive our pipeline forward, with plans to initiate first-in-human studies of CFT8634, a BRD9 degrader, and CFT1946, a BRAF V600X degrader."

RECENT HIGHLIGHTS

CFT7455: CFT7455 is a novel degrader targeting IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL), including peripheral T-cell lymphoma and mantle cell lymphoma.

Clinical Data from Cohort A and Pre-Clinical Data Characterizing the Chemical Structure of CFT7455 Accepted for Presentation at AACR (Free AACR Whitepaper): Clinical data from Cohort A, characterizing pharmacokinetic (PK) and pharmacodynamic activity alongside safety and biomarker data, has been accepted for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, hosted April 8-13, 2022. C4T will also present pre-clinical data characterizing the chemical structure of CFT7455 and the resulting improvements in potency and optimized PK properties.

Progressed CFT7455 Phase 1/2 clinical trial: Enrollment in Cohort A is complete. The ongoing Phase 1/2 trial continues to recruit patients in Cohort B1 (single agent CFT7455 in MM) and Cohort C (single agent CFT7455 in NHL).
Presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition: In December 2021, Jesus G. Berdeja, M.D., director, multiple myeloma research at Sarah Cannon Research Institute, presented a trial-in-progress poster for the CFT7455 Phase 1/2 trial.
CFT8634: CFT8634 is a degrader targeting BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Pre-clinical Data Accepted for Presentation at AACR (Free AACR Whitepaper): C4T will present pre-clinical data on the discovery and characterization of CFT8634.
Obtained FDA Clearance of IND Application for CFT8634: In December 2021, the U.S. Food and Drug Administration (FDA) cleared C4T’s investigational new drug (IND) application for CFT8634 and granted approval for C4T to proceed with the proposed Phase 1/2 trial, for which site activation efforts have commenced and the trial remains on track to begin dosing patients in 1H 2022.
Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered a presentation describing the multiparameter optimization of a series of BRD9 degraders, which led to the identification of a degrader with a sufficient intravenous PK profile to enable in vivo proof-of-concept studies. This work served as a launching point for further optimization and eventually led to the discovery of CFT8634.
CFT1946: CFT1946 is a mutant-selective degrader of BRAF V600X for the treatment of V600 mutant solid tumors.

Pre-clinical Data Accepted for Presentation at AACR (Free AACR Whitepaper): C4T will present pre-clinical data on the discovery and characterization of CFT1946.
CFT8919: CFT8919 is a potent and selective degrader of EGFR L858R for the treatment of non-small cell lung cancer.

Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered an encore presentation of the Company’s June presentation at the Keystone Symposium on targeted protein degradation. The presentation included pre-clinical data demonstrating CFT8919 is active in in vitro and in vivo models of acquired resistance to approved EGFR inhibitors that harbor resistance-causing secondary mutations in EGFR.
KEY UPCOMING MILESTONES

The company plans to achieve the following milestones in 2022:

CFT7455

Present clinical data from Cohort A of ongoing Phase 1/2 trial of CFT7455 at the AACR (Free AACR Whitepaper) Annual Meeting.
Present pre-clinical data characterizing the chemical structure of CFT7455 and the resulting improvements in potency and optimized PK properties at the AACR (Free AACR Whitepaper) Annual Meeting.
Progress CFT7455 Phase 1/2 trial toward identifying a recommended Phase 2 dose for MM and NHL.
CFT8634

Present pre-clinical data on the discovery and characterization of CFT8634 in synovial sarcoma at the AACR (Free AACR Whitepaper) Annual Meeting.
Initiate a Phase 1 trial for CFT8634 in synovial sarcoma and SMARCB1-null solid tumors in 1H 2022.
CFT1946

Present pre-clinical data on the discovery and characterization of CFT1946 in BRAF V600X driven cancers at the AACR (Free AACR Whitepaper) Annual Meeting.
Submit an IND application and initiate a Phase 1 trial of CFT1946 in BRAF V600X-driven cancers including melanoma, colorectal and non-small cell lung cancer in 2H 2022.
CFT8919

Complete IND-enabling activities for CFT8919 by year-end 2022.
UPCOMING INVESTOR EVENTS

C4T will participate in the following upcoming investor conferences:

February 24, 2022 – BMO Biopharma Spotlight Series: Protein Degraders and Other Next Gen Technologies
March 9, 2022 – Cowen & Co. 42nd Annual Health Care Conference
March 16, 2022 – Guggenheim Targeted Protein Degradation Day
March 17, 2022 – Oppenheimer’s 32nd Annual Healthcare Conference
FULL YEAR 2021 FINANCIAL RESULTS

Revenue: Total revenue for the year ended December 31, 2021 was $45.8 million, compared to $33.2 million for the year ended December 31, 2020. Total revenue reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico. The increase in revenue was primarily driven by the recognition of all previously unrecognized consideration allocated to the BRAF program upon the termination of the Roche agreement as related to that target.

Research and Development (R&D) Expense: R&D expense for the year ended December 31, 2021 was $94.7 million, compared to $78.4 million for the year ended December 31, 2020. The increase in R&D expense was primarily attributable to clinical costs incurred during the year, an increase in preclinical costs related to our lead programs, and increased workforce expenses to support our growing clinical development activities.

General and Administrative (G&A) Expense: G&A expense for the year ended December 31, 2021 was $33.3 million, compared to $15.2 million for the year ended December 31, 2020. The increase in G&A expense was primarily attributable to increased workforce expenses from our growing G&A function, and higher professional fees and insurance costs resulting from our transition to a public company in October 2020.

Net Loss and Net Loss per Share: Net loss for the year ended December 31, 2021 was $83.9 million, compared to $66.3 million for the year ended December 31, 2020. Net loss per share for the year ended December 31, 2021 was $1.82, compared to $5.83 for the year ended December 31, 2020. The decrease in net loss per share despite the increase in net loss was driven by a significant increase in the weighted-average shares outstanding from 11,370,328 as of December 31, 2020 to 46,041,733 as of December 31, 2021. This increase in shares outstanding was caused by our initial public offering of 11,040,000 common shares in October 2020 and the resultant conversion of then outstanding shares of redeemable convertible preferred stock into 30,355,379 shares of common stock, together with our issuance of 4,887,500 shares of common stock upon the closing of our follow-on public offering in June 2021.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of December 31, 2021 were $451.5 million, compared to $371.7 million as of December 31, 2020. The change in cash was primarily driven by net proceeds from our June 2021 follow-on public offering of $169.5 million, offset by expenditures to fund operations. C4T expects that its cash, cash equivalents and marketable securities as of December 31, 2021, together with future payments expected to be received under existing collaboration agreements, will be sufficient to fund planned operating expenses and capital expenditures to the end of 2024.