On January 7, 2025 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize more effective and better tolerated therapies for cancer patients, reported a positive data update from three pancreatic cancer arms of its ongoing Phase 2a trial of lead program IMM-1-104, as well as plans to expand the Phase 2a trial to include three additional combination arms (Press release, Immuneering, JAN 7, 2025, View Source [SID1234649467]). While approved MEK inhibitors mainly benefit a subset of patients with BRAF-driven tumors, IMM-1-104 was designed to improve tolerability and expand indications to include RAS-mutated tumors such as those found in most pancreatic cancers.

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"We are excited to report an updated ORR of 43% and DCR of 86% for IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients. For reference, the benchmark reported for gemcitabine/nab-paclitaxel in this setting had an ORR of 23% and DCR of 48%. We look forward to reporting further data in the second quarter of 2025 and have started planning for a potential pivotal clinical trial," said Ben Zeskind, Ph.D., CEO of Immuneering.

Dr. Zeskind continued: "Today we are also sharing initial data from IMM-1-104 in combination with modified FOLFIRINOX in first-line pancreatic cancer patients. We observed target lesion shrinkage across all evaluable patients, including a 100% reduction, a rare event in this patient population. Additionally, we are reporting initial data from our monotherapy arm of IMM-1-104 in second-line pancreatic cancer. We saw clear activity, including a partial response with a 67% target lesion reduction. We believe these results provide substantiating evidence of IMM-1-104’s contribution in combination with current therapies."

Dr. Zeskind concluded: "Importantly, we continue to observe a highly differentiated safety profile for IMM-1-104, which we designed to be better tolerated and more active than existing approved MEK inhibitors already driving annual net sales of ~$2.4 billion in 2023. Accordingly, we plan to add three new Phase 2a combination arms: IMM-1-104 with a BRAF inhibitor in BRAF-mutant melanoma, and IMM-1-104 with an immune checkpoint inhibitor in both melanoma and NSCLC. We expect to initiate these arms in 2025. Today we are setting a path to break new ground in indications where no MEK inhibitors have been approved, including pancreatic cancer, and aim to provide a better tolerated and more effective alternative where MEK inhibitors are already helping patients."

Updated Data from Phase 2a Arm Evaluating IMM-1-104 with Modified Gemcitabine/nab-Paclitaxel in First Line Pancreatic Cancer as of December 5, 2024

As of December 5, 2024, three patients in the Phase 2a arm evaluating IMM-1-104 with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer achieved complete or partial responses for an overall response rate of 43% (3/7) and disease control rate of 86% (6/7). Four patients remain on treatment.
Benchmarks for gemcitabine/nab-paclitaxel alone in first-line pancreatic cancer patients were established by the Phase 3 MPACT study, which included 1 Complete Response (CR) out of 431 patients, a 23% Overall Response Rate, and a 48% Disease Control Rate1. Benchmarks for modified (m) Gemcitabine/nab-Paclitaxel, the less intensive regimen utilized in the IMM-1-104 Phase 2 combination arm, include an 18.6% ORR2.
A favorable tolerability profile was observed for IMM-1-104 in combination with modified Gemcitabine/nab-Paclitaxel.
[1] Von Hoff, et al. N Engl J Med 2013;369:1691-1703, [2] Ahn DH, et al. Therapeutic Advances in Medical Oncology. 2017;9(2):75-82

"Immuneering’s Phase 2a data in first-line pancreatic cancer are very promising," said Tanios Bekaii-Saab, M.D., Leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center enterprise-wide and Medical Oncology consultant in Mayo Clinic in Phoenix, Arizona. "If current trends continue, the combination of IMM-1-104 with modified gemcitabine/nab-paclitaxel may provide improved efficacy and tolerability versus gemcitabine/nab-paclitaxel in the first-line pancreatic cancer setting, where patients continue to urgently need better options. In addition, having a MEK inhibitor that appears to be as well-tolerated as IMM-1-104 may provide new opportunities for patients with different types of cancer."

Initial Data from Phase 2a Arm Evaluating IMM-1-104 with Modified FOLFIRINOX in First Line Pancreatic Cancer as of December 5, 2024

As of December 5, 2024, all evaluable patients (n=4) experienced target tumor shrinkage and disease control, with one patient achieving a 100% reduction (PR).
The combination of IMM-1-104 plus modified FOLFIRINOX (mFFX) was observed to be generally well tolerated.
The Company is currently evaluating the 320 mg QD dose of IMM-1-104 in combination with modified FOLFIRINOX.
Initial Data from Phase 2a Arm Evaluating IMM-1-104 Monotherapy in Second Line Pancreatic Cancer as of December 5, 2024

"Having demonstrated compelling activity in both the combination and monotherapy settings for pancreatic cancer, the emerging tolerability profile for IMM-1-104 is also highly promising," said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. "Looking at the table of treatment-related adverse events observed in greater than 10% of patients in our monotherapy arm, no Grade 3 or Grade 4 events were observed, and only a handful of Grade 2 events were observed. The maturing safety profile for IMM-1-104 gives us confidence that Immuneering may have developed a better tolerated MEK-inhibitor, with exciting potential for vertical, immune-modifying, and orthogonal combinations. We expect to share expanded development plans for IMM-1-104 beyond pancreatic cancer, as we continue to explore options with investigators and third parties."

As of December 5, 2024, eleven of the twenty-one evaluable patients treated in the Phase 2a arm assessing IMM-1-104 as monotherapy in second-line pancreatic cancer achieved disease control, including one patient with 67% target lesion shrinkage (PR). Nine patients remain on treatment.
IMM-1-104 monotherapy was observed to be very well tolerated in second-line pancreatic cancer patients, suggesting that IMM-1-104 may be highly suitable for both monotherapy and combination therapy.
Immuneering previously announced that IMM-1-104 received Fast Track designation from the FDA for the treatment of first- and second-line pancreatic cancer, along with orphan drug designation. The FDA also recently granted Fast Track designation for IMM-1-104 as a treatment for patients with unresectable or metastatic NRAS-mutant melanoma who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors. Today’s data update follows initial data that was presented in September 2024 on the trial’s arm studying IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer.

Today, Immuneering also announced initial pharmacokinetic, pharmacodynamic and safety data from the Phase 1 portion of the company’s Phase 1/2a trial of IMM-6-415. To date, IMM-6-415 has demonstrated its potential to induce Deep Cyclic Inhibition, and in doing so has been well tolerated – consistent with what was observed preclinically for the development candidate.

Near-Term Milestone Expectations

IMM-1-104

Further IMM-1-104 Phase 2a data expected in the second quarter of 2025
Initiation of Phase 2a arm of IMM-1-104 in combination with BRAF inhibitor in melanoma planned for 2025
Initiation of Phase 2a arms of IMM-1-104 in combination with checkpoint inhibitors in both melanoma and NSCLC planned for 2025
Conference Call

Immuneering will host a conference call and live webcast at 8:30 a.m. ET / 5:30 a.m. PT on January 7, 2025, to discuss the data and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 4497245, or from the webcast link in the "investors" section of the company’s website at www.immuneering.com A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call.