On November 1, 2023 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 financial results for the third quarter ended September 30, 2023, as well as recent business highlights (Press release, C4 Therapeutics, NOV 1, 2023, View Source [SID1234636627]).
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"Our team has progressed three clinical trials this year and generated the necessary information to enable data-based portfolio decisions, which include prioritizing the ongoing Phase 1/2 trials of CFT7455 and CFT1946," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "The CFT8634 Phase 1 dose escalation data demonstrated our ability to safely degrade a previously undruggable target, further validating our platform to design BiDAC degraders with desirable drug-like properties. Unfortunately, high levels of BRD9 degradation did not result in sufficient efficacy for highly refractory patients with synovial sarcoma and SMARCB1-null solid tumors treated with CFT8634 as a single agent; thus, the development strategy to seek registration of CFT8634 in these rare tumors is not viable for C4T. On behalf of our entire team, I would like to express my sincere thanks to all patients and their caregivers as well as clinicians involved in the CFT8634 trial."
THIRD QUARTER 2023 AND RECENT ACHIEVEMENTS
CFT7455: CFT7455 is an oral degrader of IKZF1/3 for the potential treatment of relapsed refractory multiple myeloma (R/R MM) and relapsed refractory non-Hodgkin’s lymphomas (R/R NHL).
Progressed the Phase 1/2 Clinical Trial. In October 2023, C4T announced completion of the Phase 1 dose escalation for CFT7455 as a monotherapy in R/R MM using a 14 days on/14 days off dosing schedule. Twenty-two patients were enrolled across five dose escalation cohorts for this portion of the study. The Phase 1 dose escalation evaluating CFT7455 in combination with dexamethasone in R/R MM and as a monotherapy in R/R NHL continues to progress.
CFT8634: CFT8634 is an oral degrader of BRD9 for the potential treatment of synovial sarcoma and SMARCB1-null solid tumors.
Presented Phase 1 Dose Escalation at Connective Tissue Oncology Society (CTOS) Annual Meeting. In the Phase 1 dose escalation trial, CFT8634 was dosed orally starting at 2 mg daily and escalating to 50 mg daily. At the time of the data cutoff on August 29, 2023, 32 patients were enrolled (23 synovial sarcoma and nine SMARCB1-null tumor) and 84% of these patients had more than three prior treatments. All patients were evaluated for safety, the primary endpoint.
The median duration of treatment across all cohorts was 1.8 months (range of 0-11 months). CFT8634 was generally well-tolerated. As of the cutoff date, the majority of adverse events (AEs) reported were considered mild to moderate in severity. The most common treatment-related AEs were (in decreasing frequency) fatigue, dry mouth, neutropenia, dysgeusia and anemia.
Dose proportional increases in plasma exposure were achieved and maintained after single and repeat oral administration, respectively. The calculated half-life is 10 to14 hours after oral administration. Additionally, high levels of BRD9 degradation in tumor tissue obtained at day 15 were noted across all dose levels studied.
At the time of data cutoff, eight patients had stable disease (RECIST 1.1) as best responses at eight weeks. One patient (SMARCB1-null tumor) treated at the 15mg dose had a partial response.
Portfolio Decision Not to Advance CFT8634 Beyond Phase 1 Dose Escalation. C4T has made the portfolio decision not to advance CFT8634 clinical development beyond the Phase 1 trial. In the dose escalation trial, high levels of BRD9 degradation did not result in sufficient efficacy in heavily pre-treated synovial sarcoma and SMARCB1-null solid tumor patients treated with CFT8634 as a single agent. No additional patients will be enrolled in the CFT8634 Phase 1 trial and wind down activities are expected to be complete by the end of Q1 2024.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the potential treatment of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma.
Progressed the Phase 1/2 Clinical Trial. The dose escalation portion of the CFT1946 Phase 1/2 clinical trial continues in solid tumors with BRAF V600 mutations, including NSCLC, CRC and melanoma.
Advanced Translational Work with CFT1946 in Preclinical CRC Models. Ongoing translational work in preclinical CRC models encoding BRAF V600X mutations has shown promising single agent CFT1946 anti-tumor effects.
CFT8919: CFT8919 is an oral degrader designed to be potent and selective against EGFR L858R mutations for the potential treatment of non-small cell lung cancer (NSCLC).
Clinical Trial Application (CTA) Accepted for Review by China National Medical Products Administration (NMPA). Betta Pharmaceuticals announced that their CTA submission for CFT8919 has been accepted for review by China NMPA.
COLLABORATION AND RESEARCH UPDATES
Presented at the 6th Annual Targeted Protein Degradation (TPD) Summit. In October 2023, C4T delivered a presentation at the TPD Summit that highlighted the evolution of the TORPEDO platform to include chemoproteomic approaches to identify covalent ligands to both novel targets and E3 ligases.
Betta Pharmaceuticals Stock Purchase Agreement. While both C4T and Betta Pharmaceuticals have met all closing conditions under the Betta Pharmaceuticals Stock Purchase Agreement, including Overseas Direct Investment (ODI) approval, Betta Pharmaceuticals has not fulfilled their obligation to fund the $25 million equity purchase for reasons Betta Pharmaceuticals has attributed to their own business circumstances. C4T and Betta Pharmaceuticals continue to collaborate on the development of CFT8919 under the separate License and Collaboration Agreement.
CORPORATE UPDATES
In September 2023, C4T appointed Kendra Adams as chief financial officer. Ms. Adams has more than twenty-five years of experience in financial, operational and strategic planning.
UPCOMING DATA PRESENTATION
CFT7455: Present data from the Phase 1 dose escalation portion of the ongoing Phase 1/2 clinical trial focusing on CFT7455 as a monotherapy in R/R MM on December 12 at 4:30 PM ET at a virtual company-sponsored event.
UPCOMING INVESTOR EVENTS
November 8, 2023: Management will participate in the virtual BMO Biopharma Spotlight Series Oncology Day.
November 14, 2023 at 3:00 PM ET: Management will participate in a fireside chat at the Stifel 2023 Conference taking place in New York, NY.
THIRD QUARTER 2023 FINANCIAL RESULTS
Revenue: Total revenue for the third quarter of 2023 was $11.1 million, compared to $6.8 million for the third quarter of 2022. The increase in revenue was primarily due to the completion of research activities on a nominated target under the Roche Agreement. Total revenue for the third quarter of 2023 reflects revenue recognized under collaboration agreements with Roche and Biogen, and total revenue recognized in the third quarter of 2022 reflects revenue recognized under collaborations agreements with Roche, Biogen and Calico.
Research and Development (R&D) Expense: R&D expense for the third quarter of 2023 was $28.3 million, compared to $29.7 million for the third quarter of 2022. The reduction in R&D expense was due to a decrease in preclinical expenses as programs progressed through the clinic.
General and Administrative (G&A) Expense: G&A expense for the third quarter of 2023 was $10.5 million, compared to $9.6 million for the third quarter of 2022. The increase in G&A expense was attributable to stock compensation expense.
Net Loss and Net Loss per Share: Net loss for the third quarter of 2023 was $27.0 million, compared to $32.0 million for the third quarter of 2022. Net loss per share for the third quarter of 2023 was $0.55 compared to $0.65 for the third quarter of 2022.
Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of September 30, 2023, were $246.4 million, compared to $337.1 million as of December 31, 2022. The decrease in cash was attributable to ongoing operating expenses as well as the early payment of the outstanding principal balance of the term loan held with Perceptive Advisors of $12.5 million. C4T expects that its cash, cash equivalents and marketable securities as of September 30, 2023, will be sufficient to fund planned operating expenses and capital expenditures into the second half of 2025.