Erasca to Present Promising Preliminary HERKULES-3 Phase 1b Data at the 2023 ASCO Annual Meeting

Triplet of ERAS-007 100 mg BID-QW + encorafenib + cetuximab (EC) in EC-naïve patients with metastatic BRAF V600E-mutated colorectal cancer (CRC) showed a 40% (2/5) response rate; continued evaluation of this combination will focus on EC-naïve patients based on promising initial activity

ERAS-007 in combination with cell cycle inhibitor palbociclib will not be pursued further in patients with RAS-mutated gastrointestinal (GI) malignancies

Erasca to host investor event on June 5, 2023, at 4:30 PM Eastern Time

SAN DIEGO, May 25, 2023 (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 preliminary Phase 1b data for ERAS-007 combinations in patients with GI malignancies from two poster presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. The posters will be available online at .

“Early clinical data from HERKULES-3 continue to reinforce the potential to combine ERAS-007 with multiple agents and its potential as a backbone therapy to treat patients with GI malignancies. Importantly, these preliminary findings support a data-driven approach to refine the focus of our initial clinical development efforts on indications holding significant promise,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “Our initial evaluation of the ERAS-007 + EC combination in patients with BRAF-mutated metastatic CRC will focus on EC-naïve patients based on the preliminary activity observed in HERKULES-3. By evaluating efficacy and safety in a larger sample size of patients treated at the 100 mg BID-QW dose of ERAS-007 with EC, we believe we will be able to better assess whether the promising response rate and duration of treatment observed with the triplet can be maintained.”

Poster Presentation Highlights

– Preliminary results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with metastatic BRAF V600E-mutated colorectal cancer (CRC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)

ERAS-007 in combination with encorafenib (BRAFTOVI^®) + cetuximab (ERBITUX^®) demonstrated promising preliminary clinical activity in EC-naïve patients with metastatic BRAF V600E-mutated CRC. EC is currently approved for the treatment of patients with metastatic BRAF V600E-mutated CRC, as detected by an FDA-approved test, after prior therapy; however, only approximately 20% of patients experience an objective response in the second and later line of treatment setting. Downstream ERK inhibition through ERAS-007 may prevent resistance to upstream BRAF/EGFR inhibition when combined with EC. As of the data cutoff date of March 23, 2023:

• 40% (2/5) response rate and 60% (3/5) disease control rate (complete response + partial response + stable disease) in EC-naïve response evaluable patients at the highest dose of ERAS-007 tested (100 mg BID-QW), with duration of exposure for both responders > 34 weeks as of the data cutoff date; across all dose levels in EC-naïve response evaluable patients, 29% (2/7) response rate and 57% (4/7) disease control rate
• ERAS-007 + EC was generally well-tolerated with mostly low-grade adverse events at all combination doses tested
• One dose-limiting toxicity (DLT) was reported for ERAS-007 100 mg BID-QW + EC (Grade 3 macular edema)
• Pharmacokinetic (PK) exposures of ERAS-007, encorafenib, and cetuximab were comparable to monotherapy values, suggesting no clinically significant PK drug-drug interactions between the study drugs

Additional HERKULES-3 Phase 1b combination data in EC-naïve patients with BRAF-mutated CRC expected between H2 2023 and H1 2024

– Preliminary results from ERAS-007 plus palbociclib (palbo) in patients (pts) with KRAS/NRAS mutant (m) colorectal cancer (CRC) or KRASm pancreatic ductal adenocarcinoma (PDAC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)

ERAS-007 in combination with palbociclib (IBRANCE^®) demonstrated a lack of clinical activity in patients with KRAS/NRAS mutant CRC and KRAS mutant PDAC. Palbociclib is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy or with fulvestrant in patients with disease progression following endocrine therapy. Based on these data, the combination of ERAS-007 and palbociclib will not be pursued further in this patient population.

Dr. Lim continued, “Our pioneering efforts exploring the potential of targeting adjacent pathways with terminal node inhibition of the RAS/MAPK pathway (ERAS-007) and cell cycle inhibition (palbociclib) did not demonstrate clinical activity in the initial evaluation. While we will not pursue further development of this combination in this patient population, it has contributed to our understanding and characterization of ERAS-007.”

About Erasca

At 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 what we believe to be the deepest RAS/MAPK pathway-focused pipeline 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 and safety profile of our product candidates, including ERAS-007; and the planned advancement of our development pipeline, including the anticipated timing of future data readouts for the HERKULES-3 trial, and other upcoming development milestones. 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: preliminary results of a clinical trial 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 as more patient data becomes available; 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; potential delays in the commencement, enrollment, 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; results from preclinical studies or early clinical trials not necessarily being predictive of future results; regulatory developments in the United States and foreign countries; 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 ending December 31, 2022, 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.

IBRANCE^® (palbociclib) and BRAFTOVI^® (encorafenib) are each a registered trademark owned by or licensed to Pfizer Inc., its subsidiaries, or affiliates.

ERBITUX^® (cetuximab) is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

Contact:

Joyce Allaire

LifeSci Advisors, LLC

Source: Erasca, Inc.