Trametinib dimethyl sulfoxide

Cemsidomide Phase 1/2 Trial in Multiple Myeloma and non-Hodgkin’s Lymphoma Continues to Progress: Data from Both Indications to be Presented at the 66th American Society of Hematology (ASH) Annual Meeting in San Diego, CA Initial Monotherapy CFT1946 Phase 1 Data Demonstrated Well-Tolerated Safety Profile and Early Evidence of Anti-tumor Activity; Phase 1/2 Trial Continues to Progress with Multiple Data Readouts Expected in 2025 Appointed Paige Mahaney, Ph.D. as Chief Scientific Officer Bringing More than 25 Years of Pharmaceutical and Biotech Experience Cash, Cash Equivalents and Marketable Securities of $284.4 million as of September 30, 2024; Expected to Provide Runway into 2027 WATERTOWN, Mass., Oct. 31, 2024 (GLOBE NEWSWIRE) -- C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported financial results today for the third quarter ended September 30, 2024, as well as recent business highlights. “2024 has been a successful year for C4T marked by strong execution across our entire portfolio, which has continued to position us as a leader in targeted protein degradation science. We recently shared initial clinical data on CFT1946 demonstrating a well-tolerated safety profile and evidence of monotherapy anti-tumor activity in BRAF inhibitor exposed patients, and we delivered our second development candidate to Biogen,” said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. “We look forward to continuing this momentum with cemsidomide Phase 1 data in multiple myeloma and in non-Hodgkin’s lymphoma being presented at ASH, and multiple CFT1946 data readouts expected in 2025. Our continued focus on discovery research, clinical development and collaborations sets us up for an exciting future and for the potential to improve patients’ lives.” THIRD QUARTER 2024 AND RECENT ACHIEVEMENTS Cemsidomide: Cemsidomide is an oral degrader of IKZF1/3 for the potential treatment of relapsed/refractory (R/R) multiple myeloma (MM) and R/R non-Hodgkin’s lymphoma (NHL). Advanced the Phase 1/2 Clinical Trial. The cemsidomide Phase 1/2 trial in combination with dexamethasone for R/R MM and as a monotherapy for R/R NHL continues to enroll patients. Dose escalation continues as the maximum tolerated dose has not yet been reached. For the combination with dexamethasone MM arm, patients are now enrolling at dose level 6 (100 µg once daily (QD)) and enrollment in the dose level 5 (75 µg QD) expansion cohort is complete. The monotherapy NHL arm continues to progress and dose level 5 (100 µg QD) is the highest dose level evaluated to date. CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the potential treatment of solid tumors including colorectal cancer (CRC), melanoma and non-small cell lung cancer (NSCLC). Presented New Preclinical Data at the 7th Annual Targeted Protein Degradation (TPD) Summit: In October 2024, C4T shared new in vivo data for CFT1946 describing Kpu,u (range: 0.34 - 0.88), experimentally determined using independent methods in two different species. These results demonstrate CFT1946’s ability to cross the blood brain barrier and highlight the potential for activity in primary and metastatic central nervous system (CNS) disease.Presented Monotherapy Clinical Data Demonstrating Proof of Mechanism and Early Evidence of Proof of Concept from the Ongoing CFT1946 Phase 1 Trial at the European Society for Medical Oncology (ESMO) Congress 2024: CFT1946 demonstrated a well-tolerated safety profile and evidence of monotherapy anti-tumor activity, which supports further clinical development as monotherapy and in combination with MEK and EGFR targeted therapies.Advanced the Phase 1/2 Clinical Trial. The CFT1946 Phase 1/2 trial for BRAF V600 mutant solid tumors continues to enroll patients across multiple arms of the trial: CFT1946 Monotherapy Dose Escalation in BRAF V600 Mutant Solid Tumors: Patients continue to enroll in the 640 mg twice daily (BID) pharmacodynamic (PD) backfill cohort.CFT1946 Monotherapy Melanoma Expansion Cohorts: Enrollment at the 320 mg BID dose level is complete and patients are enrolling at the 640 mg BID dose level.CFT1946 with Cetuximab Phase 1b Dose Escalation for CRC: The 160 mg BID dose level has been declared safe and patients are enrolling at the 320 mg BID dose level. RESEARCH UPDATES: Presented at the 7th Annual TPD Summit Highlighting C4T’s TORPEDO® Platform: In October 2024, at the 7th Annual TPD Summit, C4T presented kinetics-based pharmacokinetic (PK) and PD models, demonstrating the company’s ability to predict clinical PD responses across target classes. COLLABORATIONS: Delivered Second Development Candidate to Biogen. In September 2024, C4T earned an additional $8 million milestone payment after Biogen accepted delivery of a second development candidate in an undisclosed indication. Biogen is responsible for all future clinical development and commercialization for this program. This marks the final development candidate under this strategic collaboration. CORPORATE UPDATES: In October 2024, C4T appointed Paige Mahaney, Ph.D., as the company’s chief scientific officer, succeeding Stew Fisher, Ph.D., who is retiring to pursue personal interests. Dr. Mahaney brings over 25 years of pharmaceutical executive leadership with multidisciplinary expertise in discovery research and development along with successfully building clinical portfolios across a wide range of disease indications and treatment modalities.In September 2024, C4T appointed Stephen Fawell, Ph.D., to the Board of Directors. Dr. Fawell brings decades of experience leading discovery and development strategies for global pharmaceutical companies. KEY UPCOMING MILESTONES Cemsidomide: Present updated dose escalation and expansion cohort data from the 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 75 µg QD dose levels in approximately 40 patients from the ongoing Phase 1/2 clinical trial with dexamethasone in R/R MM at the ASH Annual Meeting in December 2024.Present dose escalation data from the 25 µg M/W/F, 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 100 µg QD dose levels in approximately 25 patients from the ongoing monotherapy Phase 1/2 clinical trial in R/R NHL at the ASH Annual Meeting in December 2024.Complete Phase 1 dose exploration in R/R MM and R/R NHL by year-end. CFT1946: Initiate the Phase 1b dose escalation cohort evaluating CFT1946 in combination with trametinib in melanoma by year-end.Present data from multiple anticipated readouts in 2025, including: Full monotherapy CFT1946 dose escalation cohorts in BRAF V600 mutant solid tumors.Expansion cohorts evaluating CFT1946 as a monotherapy in melanoma.Phase 1b dose escalation cohort evaluating CFT1946 in combination with cetuximab in CRC. UPCOMING INVESTOR EVENTS: November 20, 2024, at 8 am GT: Management will participate in a fireside chat at the Jefferies London Healthcare conference taking place in London, UK.December 8, 2024: Management will host an investor call to discuss MM and NHL data from the ongoing Phase 1/2 trial of cemsidomide. THIRD QUARTER 2024 FINANCIAL RESULTS Revenue: Total revenue for the third quarter of 2024 was $15.4 million, compared to $11.1 million for the third quarter of 2023. The increase in revenue was primarily due to recognition of an $8.0 million milestone from Biogen as well as $2.9 million of revenue recognized under our license and supply agreement with Betta, partially offset by reduced revenue from our agreement with Roche due to the completion of research activities in the third quarter of 2023 for a nominated target. Total revenue for the third quarter of 2024 reflects revenue recognized under our collaborations with Biogen, Betta, Merck, Merck KGaA, Darmstadt, Germany (MKDG) and Roche, and total revenue recognized in the third quarter of 2023 reflects revenue recognized under collaboration agreements with Biogen and Roche. Research and Development (R&D) Expense: R&D expense for the third quarter of 2024 was $31.8 million, compared to $28.3 million for the third quarter of 2023. The increase in R&D expense was primarily due to increased clinical trial expense as cemsidomide and CFT1946 continue to advance, partially offset by lower personnel costs. General and Administrative (G&A) Expense: G&A expense was $11.8 million for the third quarter of 2024, compared to $10.5 million for the third quarter of 2023. The increase in G&A expense was primarily attributable to higher personnel expense related to stock-based compensation. Net Loss and Net Loss per Share: Net loss for the third quarter of 2024 was $24.7 million, compared to $27.0 million for the third quarter of 2023. Net loss per share for the third quarter of 2024 was $0.35 compared to $0.55 for the third quarter of 2023. Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of September 30, 2024 were $284.4 million, compared to $295.7 million as of June 30, 2024, and $281.7 million as of December 31, 2023. The reduction in cash, cash equivalents and marketable securities during the third quarter was primarily the result of cash used in operating activities, partially offset by $10.3 million in net proceeds raised through our at-the-market (ATM) facility. C4T expects that its cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund planned operating expenses and capital expenditures into 2027. About C4 Therapeutics C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit www.c4therapeutics.com. About CemsidomideCemsidomide is an orally bioavailable MonoDAC® degrader designed to be highly potent and selective against its intended targets of Ikaros (IKZF1) and Aiolos (IKZF3) and overcome shortcomings of currently approved therapies to treat multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). Cemsidomide is currently in a Phase 1 dose escalation study in MM and NHL. Initial clinical data show cemsidomide is well tolerated, demonstrates anti-myeloma activity and displays evidence of immunomodulatory effects. More information about this trial may be accessed at www.clinicaltrials.gov (identifier: NCT04756726). About CFT1946CFT1946 is an orally bioavailable BiDAC™ degrader designed to be potent and selective against BRAF V600X mutant targets. In preclinical studies, CFT1946 is active in vivo and in vitro in models with BRAF V600E driven disease and in models resistant to BRAF inhibitors. CFT1946 is currently in a Phase 1 dose escalation study in BRAF V600X mutant solid tumors including colorectal cancer, melanoma and non-small cell lung cancer. More information about this trial may be accessed at www.clinicaltrials.gov (identifier: NCT05668585). Forward-Looking Statements This press release contains “forward-looking statements” of C4 Therapeutics, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, but may not be limited to, express or implied statements regarding our ability to develop potential therapies for patients; the design and potential efficacy of our therapeutic approaches; the anticipated timing and content of presentations of data from our clinical trials; and our ability to fund our future operations. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties related to the initiation, timing, advancement and conduct of preclinical and clinical studies and other development requirements for our product candidates; the risk that any one or more of our product candidates will cost more to develop or may not be successfully developed and commercialized; and the risk that sufficient capital to fund our future operations will be available to us on acceptable terms or at the times required. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in C4 Therapeutics’ most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and C4 Therapeutics undertakes no duty to update this information unless required by law. Contacts: Investors:Courtney SolbergSenior Manager, Investor RelationsCSolberg@c4therapeutics.com Media:Loraine SpreenSenior Director, Corporate Communications & Patient AdvocacyLSpreen@c4therapeutics.com Condensed Consolidated Balance Sheet Data(in thousands) (unaudited) (audited) September 30, 2024 December 31, 2023Cash, cash equivalents and marketable securities$284,400 $281,689Total assets 376,060 376,451Deferred revenue 49,417 37,285Total stockholders' equity 242,656 246,114 Condensed Consolidated Statements of Operations(in thousands, except share and per share amounts)(Unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from collaboration agreements$15,362 $11,072 $30,407 $17,495 Operating expenses: Research and development 31,838 28,347 78,124 87,315 General and administrative 11,768 10,533 31,751 31,784 Restructuring — — 2,437 — Total operating expenses 43,606 38,880 112,312 119,099 Loss from operations (28,244) (27,808) (81,905) (101,604)Other income (expense), net: Interest expense and amortization of long-term debt − related party — (167) — (1,373)Loss on early extinguishment of debt — (621) — (621)Interest and other income, net 3,578 2,562 11,162 6,862 Total other income, net 3,578 1,774 11,162 4,868 Loss before income taxes (24,666) (26,034) (70,743) (96,736)Income tax expense — (1,003) — (1,003)Net loss$(24,666) $(27,037) $(70,743) $(97,739)Net loss per share − basic and diluted$(0.35) $(0.55) $(1.03) $(1.99)Weighted-average shares outstanding − basic and diluted 69,627,190 49,212,126 68,958,938 49,103,351

Positive preliminary Phase 1b SEACRAFT-1 data for naporafenib plus trametinib reinforce therapeutic potential in NRASm melanoma and further support ongoing Phase 3 SEACRAFT-2 trial SEACRAFT-2 has potential for approval based on alignment with US and European regulatory agencies on path for tissue-specific indication in melanoma; Stage 1 randomized data expected in 2025 Rapid progress across RAS targeting franchise; planned IND submissions remain on track Erasca to host investor event today at 8:30 AM Eastern Time SAN DIEGO, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced clinical progress for naporafenib and preclinical execution across the company’s RAS targeting franchise. “The SEACRAFT-1 trial in patients with RAS Q61X solid tumors has successfully accomplished several key objectives: delivering clinical data supporting the potential for durable efficacy in patients with NRAS-mutant (NRASm) melanoma, who currently have limited treatment options following frontline immunotherapy; identifying the most promising antitumor signal for the combination, which has been observed in melanoma patients, supporting a tissue-specific approach; and reducing the frequency and severity of dermatologic toxicities through mandatory primary prophylaxis,” said Shannon R. Morris, M.D., Ph.D., Erasca’s chief medical officer. “In totality, these data strengthen our conviction in the ongoing SEACRAFT-2 Phase 3 trial, for which we gained US and European alignment on the regulatory path in patients with NRASm melanoma. We look forward to randomized dose optimization data from Stage 1 of this trial, which is expected in 2025.” Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder, added, “We were excited to bolster our pipeline with the in-licensing of our RAS-targeting franchise in May, including the pan-RAS molecular glue ERAS-0015 and the pan-KRAS inhibitor ERAS-4001. These two assets with competitive profiles, potential for significant patient benefit, and broad application across solid tumors, have become key priorities for the company. In addition to reproducing data in-house supporting the best-in-class potential of both compounds, we continue to execute effectively and efficiently across several functional disciplines, including generating additional in vivo data and progressing the in-life portion of the Good Laboratory Practice (GLP) toxicology studies as anticipated, as well as advancing our drug substance and drug product development and manufacturing activities for both molecules according to plan. Investigational new drug (IND) application submissions remain on track for the first quarter of 2025 for ERAS-4001 and the first half of 2025 for ERAS-0015.” Naporafenib Program Update Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor. Naporafenib plus trametinib (MEKINIST®) is being evaluated in the Phase 1b SEACRAFT-1 trial in patients with RAS Q61X mutations and the Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma. In a post-hoc pooled analysis of Phase 1b and Phase 2 data from trials in patients with NRASm melanoma conducted by Novartis, naporafenib in combination with trametinib demonstrated favorable median overall survival (mOS) and median progression free survival (mPFS). The U.S. Food and Drug Administration has granted Fast Track Designation to naporafenib plus trametinib for the treatment of NRASm melanoma. NRASm melanoma has a high unmet medical need 25-30% of melanomas are NRASm, which has a worse prognosis vs. other molecular alterationsCurrent treatment options following frontline immunotherapy are poor: chemotherapy (approved standard of care) demonstrated 7% ORR and 1.5 months mPFS; binimetinib demonstrated 15% ORR and 2.8 months mPFS Promising initial Phase 1b efficacy results in the SEACRAFT-1 melanoma cohort further bolsters rationale for pursuing NRASm melanoma indication*: 40% (4/10) response rate observed in the melanoma cohort, including three confirmed partial responses (cPR) and one unconfirmed partial response (uPR); the melanoma cohort in SEACRAFT-1 is representative of the patient population currently being enrolled in the pivotal SEACRAFT-2 trial70% (7/10) of patients were on treatment as of the data cutoff, including all four responders Generally well-tolerated with mostly low-grade adverse events in the majority of patients* Results suggest that mandatory primary rash prophylaxis helped reduce frequency and severity of dermatological toxicities, reduced drug discontinuation rate due to adverse events, and improved the tolerability profile as measured by an increased relative dose intensity as compared to the prior clinical trials of naporafenib plus trametinib conducted by Novartis, which did not include the use of mandatory primary rash prophylaxis Data reinforce potential of ongoing Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma Potential for approval in both US and Europe based on high unmet need and regulatory alignmentRandomized dose optimization data from Stage 1 of the SEACRAFT-2 Phase 3 trial expected in 2025 * Safety data cutoff date was September 3, 2024. Efficacy data cutoff date was September 5, 2024 RAS Targeting Franchise Update (ERAS-0015 and ERAS-4001) ERAS-0015 is a preclinical pan-RAS molecular glue with best-in-class potential for patients with RASm solid tumors that showed up to 10-fold greater potency and favorable absorption, distribution, metabolism, and excretion (ADME) properties and pharmacokinetics (PK) performance in preclinical studies when compared to another pan-RAS molecular glue currently in clinical development. ERAS-4001 is a preclinical pan-KRAS inhibitor that has shown first-in-class and best-in-class potential with high potency, strong antitumor activity, favorable ADME and PK properties in preclinical studies, including oral bioavailability, and ability to spare H/NRAS while limiting resistance through KRAS wild type activation. Nonclinical data continue to support potential best-in-class profiles, including data generated in-houseIn-life portion of Good Laboratory Practice (GLP) toxicology studies tracking as anticipated: ERAS-0015 completed, ERAS-4001 near completionOn track to achieve previously articulated guidance of IND filing in H1 2025 for ERAS-0015 and Q1 2025 for ERAS-4001 About ErascaAt Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipelines in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer.Cautionary Note Regarding Forward-Looking Statements Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including naporafenib, ERAS-0015, and ERAS-4001; the planned advancement of our development pipeline, including the anticipated timing of the data readout for Stage 1 of the SEACRAFT-2 trial, our alignment with regulatory authorities on the regulatory pathway for naporafenib, and the anticipated timing of the IND filings for ERAS-0015 and ERAS-4001. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; preliminary results of clinical trials are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data and more patient data become available; the analysis of pooled Phase 1 and Phase 2 naporafenib plus trametinib data covers two clinical trials with different designs and inclusion criteria, which cannot be directly compared, and therefore may not be a reliable indicator of survival data; due to differences between trial designs and subject characteristics, comparing data across different trials may not be a reliable indicator of data; our assumptions about ERAS-0015’s and ERAS-4001’s development potential are based in part on the preclinical data generated by the licensors and we may observe materially and adversely different results as we conduct our planned studies and trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; we only have one product candidate in clinical development and all of our other development efforts are in the preclinical or development stage; our SEACRAFT trials may not support the registration of naporafenib; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, data readout, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; the inability to realize any benefits from our current licenses, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; regulatory developments in the United States and foreign countries; later developments with the FDA or EU health authorities may be inconsistent with the feedback received to date regarding our development plans and trial designs; Fast Track Designation may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ended December 31, 2023, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. MEKINIST® is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates. Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com Source: Erasca, Inc.