Immuneering Corporation (NASDAQ:IMRX): Advancing Innovative Oncology Therapies Through Deep Cyclic Inhibition

Immuneering Corporation (NASDAQ:IMRX) is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients. The company's inclusive approach, which aims to achieve universal activity through Deep Cyclic Inhibition (DCI) of the MAPK pathway, differentiates it from narrowly targeted precision therapies.

Business Overview

Immuneering is currently evaluating its lead product candidate IMM-1-104, as well as its second product candidate IMM-6-415, in Phase 1/2a clinical trials in patients with advanced solid tumors harboring RAS and RAS/RAF mutations, respectively. IMM-1-104 is being developed as a potential once-daily oral therapy that aims to achieve universal-RAS activity through DCI of the MAPK pathway, while IMM-6-415 aims to achieve universal-RAS/RAF activity with an accelerated twice-daily oral dosing cadence, also through DCI of the MAPK pathway.

The company's development pipeline also includes several early-stage programs. Immuneering's proprietary, human-aligned 3D tumor modeling platform, combined with bioinformatics-driven patient profiling, is used to guide the translational development of its pipeline.

Financials

For the fiscal year ended December 31, 2023, Immuneering reported a net loss of $53.5 million and no revenue. The company's annual operating cash flow was -$48.9 million, and its annual free cash flow was -$49.3 million.

In the first quarter of 2024, the company reported a net loss of $14.3 million. Research and development expenses increased by approximately $1.0 million, or 9.7%, to $11.2 million, while general and administrative expenses decreased by approximately $0.3 million, or 7.7%, to $4.1 million compared to the same period in 2023.

As of March 31, 2024, Immuneering had $71.3 million in cash, cash equivalents and marketable securities, which the company believes will be sufficient to fund its development activities and other operations into the second half of 2025.

Universal-RAS Program (IMM-1-104)

In September 2022, the FDA cleared Immuneering's IND application for IMM-1-104. In November 2022, the company commenced dosing in the Phase 1 portion of its Phase 1/2a clinical trial of IMM-1-104 for the potential treatment of patients with advanced RAS mutant solid tumors, and in March 2024 it commenced dosing in the Phase 2a portion.

The Phase 1/2a clinical trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of IMM-1-104. In November 2023, Immuneering announced that it had expanded the IMM-1-104 Phase 1/2a clinical trial design by increasing the number of Phase 2a expansion arms to five, including two combination therapy arms and three monotherapy arms.

In March 2024, the company announced positive topline results from the Phase 1 portion of the Phase 1/2a clinical trial of IMM-1-104. As of February 20, 2024 (N=41), IMM-1-104 was well-tolerated, with no grade 4 treatment-related adverse events (TRAEs) observed and only one grade 3 TRAE. The company also observed a number of grade 1 TRAEs, with diarrhea, nausea, fatigue and vomiting being the most common. Additionally, patient plasma data showed IMM-1-104 inhibiting phosphorylated extracellular signal-regulated kinase (pERK) at a level of 90% or greater for approximately 2.7 hours at the 320 mg dose and 1.9 hours at the 240 mg dose, before returning to near-zero levels in advance of 24 hours. Based on these results, Immuneering selected a candidate recommended Phase 2 dose (RP2D) of 320 mg once daily.

As of February 20, 2024 (N=22), 100% of evaluable patients profiled by circulating tumor DNA (ctDNA) and treated with IMM-1-104 experienced no new acquired alterations in RAS, suggesting that there was no mutation in the MAPK pathway that a tumor could use to evade IMM-1-104. While clinical activity was not an endpoint of the Phase 1 portion, the company observed that 53% of patients had ≥ 1 target lesion(s) regress when treated with IMM-1-104 at either 320 mg or 240 mg, with best individual lesion regressions of -35.7% at 320 mg and -11.4% at 240 mg.

Immuneering plans to announce initial data from multiple arms of the Phase 2a portion of the IMM-1-104 trial in 2024.

Universal-RAS/RAF Program (IMM-6-415)

In December 2023, the FDA cleared Immuneering's IND application for IMM-6-415, and in March 2024, the company commenced dosing in the Phase 1 portion of its Phase 1/2a clinical trial of IMM-6-415 for the potential treatment of patients with advanced solid tumors harboring RAF or RAS mutations. The Phase 1/2a clinical trial is designed to assess the safety, tolerability, PK, PD, and preliminary anti-tumor activity of IMM-6-415. Immuneering plans to provide initial PK, PD and safety data from the Phase 1 portion of this trial in 2024.

Liquidity

On April 20, 2023, Immuneering completed an underwritten follow-on equity offering, raising $28.2 million in net proceeds after deducting underwriting discounts and commissions. As of March 31, 2024, the company had $71.3 million in cash, cash equivalents and marketable securities, which it believes will be sufficient to fund its development activities and other operations into the second half of 2025.

Risks and Challenges

Immuneering faces several risks and challenges common to clinical-stage biotechnology companies, including the inherent uncertainties of drug development, the need for additional capital to fund its operations, and competition from other companies developing therapies targeting the MAPK pathway. The company also faces risks related to its reliance on third-party service providers, potential manufacturing challenges, and the need to successfully navigate the regulatory approval process.

Conclusion

Immuneering is a clinical-stage oncology company with a unique approach to targeting the MAPK pathway through Deep Cyclic Inhibition. The company's lead product candidates, IMM-1-104 and IMM-6-415, are currently in Phase 1/2a clinical trials, and the company has reported promising early data for IMM-1-104. With a strong financial position and a pipeline of innovative product candidates, Immuneering is well-positioned to continue advancing its mission of developing universal-RAS/RAF medicines for broad populations of cancer patients.