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]).

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"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.