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immune company (NASDAQ: IMRX) just reported positive results from the Phase 1 portion of its Phase 1/2 study using IMM-1-104 to treat patients with RAS-mutant solid tumors.Specifically, a large proportion of these patients had pancreatic cancer, followed by Other solid tumors with expression of this mutation. Preliminary data demonstrated favorable safety and anti-tumor activity, while finding a favorable recommended phase 2 dose (RP2D) for continued use. Even though this catalyst has passed, that doesn’t mean investors can’t benefit again from another catalyst later related to the program. how so? This is because the purpose of this preliminary study is only to observe the safety, PK, PD and some anti-tumor effects of IMM-1-104. Also, this is a basket study.The biotech aims to publish more results from the extension part of its Phase 1/2a study using the drug The other five cohorts will launch in March 2024.
Such data is expected to be released later this year and, if positive, could result in significant gains for investors. The first three cohorts will use IMM-1-104 as monotherapy to treat specific RAS-mutated solid tumors, and then the other two cohorts will include using the drug in combination with other drugs to treat patients with RAS-mutated non-small cell lung cancer. (NSCLC). The problem is, IMM-1-104 is just one drug in development for once-daily dosing in patients with RAS mutations. However, there is another drug in development with greater potential: IMM-6-415. This results in targeting RAS and RAF mutant solid tumors and the ability to achieve this through BID (twice daily) dosing.
TD Cowen Analyst Downgraded Immunity Rating to Market Performance Rating, noted that the monotherapy data were not different compared to other RAS inhibitors in the field. My take on this is that they still have a “market perform” rating and still state that they achieve an excellent safety profile. Therefore, you can still do well in using the IMM-1-104 in combination. As I will show below, it combines IMM-1-104 with mFOLFIRINOX and gemcitabine/paclitaxel to treat patients with first-line pancreatic ductal adenocarcinoma (PDAC). Despite the downgrade, I still believe this company has proven its mechanism of action by targeting the MAPK pathway in treating tumors. With additional data from IMM-1-104 in patients with RAS-mutant solid tumors, plus additional data from 5 other cohorts due to be released in 2024, I believe investors can benefit from any potential gains.
IMM-1-104 for the treatment of patients with RAS mutated solid tumors
As I said above, Immuneering just released the results of the first phase Phase 1/2a study, using IMM-1-104 to treat patients with RAS-mutated solid tumors. This is to achieve several preliminary measurements such as: pharmacokinetics (PK), pharmacodynamics (PD), circulating tumor DNA (ctDNA), and initial antitumor activity. This particular study enrolled eight different solid tumor types with RAS mutations. However, a large proportion of people (60%) develop pancreatic cancer. As I will show below, this population is important because two of the five phase 1/2a expansion cohorts targeted patients with RAS-mutated non-small cell lung cancer (NSCLC). What was revealed was that the study did not include clinical activity as an endpoint, but that didn’t matter because what was revealed was pretty good.First, more than 50% of patients received IMM-1-104 at the 320 mg or 240 mg QD dose Regression of tumor lesions has been achieved. In patients with second-line RAS-mutant solid tumors, the best outcome for individual tumor regression was -35.7% with 320 mg of the drug. I believe this drug has the potential to have a huge impact in the treatment of RAS-mutated solid tumors. Not only because of the preliminary efficacy achieved, but also because of the ability of the drug to inhibit RAS changes. Notably, acquired RAS alterations were completely suppressed (100%) when ctDNA was assessed. Why is this discovery important? First, it is shown that universal RAS MAPK pathway targeting is achieved. So this leads to the second positive term in this result, which is the ability to suppress resistance mechanisms. Many patients treated for RAS-mutant solid tumors acquire multiple MAPK pathway resistance mechanisms during the process. Because IMM-1-104 is able to inhibit such acquired RAS changes, it could theoretically provide more substantial clinical results.
That’s a pretty good result for the Phase 1 portion of a Phase 1/2a study using IMM-1-104 to treat patients with RAS-mutant solid tumors. Especially when you consider that 80% of patients with metastatic disease also never respond to any prior treatment. Due to the large number of patients suffering from pancreatic cancer, this may be a key focus for the company.The first reason is FDA Grants IMM-1-104 Fast Track Designation used to treat this specific patient population. The second reason is because as I said above, two of the five cohorts will have zero treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The Phase 2a combination expansion port of the trial is evaluating 60 first-line PDAC patients in the first-line setting, as follows:
- IMM-1-104 + mFOLFIRINOX (30 patients)
- IMM-1-104 + gemcitabine and nab-paclitaxel (30 patients)
Three other cohorts are being deployed using IMM-1-104 as monotherapy in PDAC, RAS-mutant melanoma, and RAS-mutant NSCLC. The plan has two catalysts to look forward to. The first is the release of Phase 1/2a expansion cohort data of IMM-1-104 in RAS-mutant solid tumors. The goal is to use the implemented RP2D and deploy it in monotherapies and combination therapies as shown above and generate additional data. These data are expected to be released later in 2024, and I believe the positive data released could cause the stock price to move higher. A smaller catalyst may be the recently released data from the Phase 1 portion of a Phase 1/2a study using the drug to treat several patients with RAS-mutated solid tumors. This is also expected to occur during the same period.
finance
according to 10-K SEC FilingAs of December 31, 2023, Immuneering had $85.7 million in cash, cash equivalents and marketable securities. The reason for the cash on hand is its ability to raise $30 million through an underwritten public offering. At that time, it sold 2,727,273 shares of Class A common stock at an offering price of $11 per share. Net proceeds from the public offering, after deducting expenses, totaled $28.2 million. This biotech has been in good shape for quite some time, especially when you consider the projections it has provided. It believes it has enough cash on hand to fund its operations into the second half of 2025. The only way I can see this biotech launching another cash-raising campaign is if positive data from the second phase of the IMM-1-104 Phase 1/2a study is released later this year, causing the stock price to rise. Then, I believe management will take advantage of this upside and raise cash sooner than expected.
business risk
Investors should be aware of some risks before investing in Immuneering Corporation. The first risk to consider is the progression of IMM-1-104 in patients with RAS-mutant solid tumors. Although initial data from the Phase 1 portion of the Phase 1/2a study yielded initially positive safety and antitumor activity, there is no assurance that the same will occur in the 5 expansion cohorts being evaluated. Additionally, the company aims to see if IMM-1-104 can achieve superior efficacy data when combined with either of two typical first-line therapies for pancreatic cancer patients. There is no guarantee that combining IMM-1-104 with mFOLFIRINOX or gemcitabine/nab-paclitaxel will produce the desired results in patients with PDAC.
A second risk to consider is the progression of IMM-6-415 in patients with RAS/RAF mutated solid tumors. They believe the drug can effectively target both MAPK pathways, but there is no guarantee it will do this. The clinical candidate has a short half-life, allowing it to be administered twice daily. This alternative approach may be feasible, enabling patients to be dosed with IMM-6-415 twice daily, but it is impossible to know whether any significant tolerability issues would arise as a result. The drug is also expected to be co-developed with other drugs in the hope of helping to improve clinical outcomes against RAS/RAF mutated solid tumors. While the drug may ultimately prove effective as a monotherapy in treating such patients, there’s no guarantee that combination therapy will ultimately yield better data.
The third risk to consider is competitors in the field. Based on the preliminary data the company has released so far, I see huge potential here, primarily the ability to suppress acquired changes in RAS in 100% of patients. This is crucial because the last thing patients need is for the cancer itself to develop resistance mechanisms during treatment.The first competitor is Bristol-Myers Squibb (BMY) With Krazzati, this is FDA approved Indicated for patients with KRAS G12C locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. Another competitor in the field of RAS mutation pathways is Amgen (AMGN) in collaboration with Lumakras, which is also FDA-approved for the treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC after first-line therapy. Nonetheless, these biotechnologies focus on KRAS G12C as part of the RAS mutation pathway.
in conclusion
Immuneering Corporation has been able to establish preliminary anti-tumor activity with its IMM-1-104 drug in patients with RAS mutations in the Phase 1 portion of a Phase 1/2a study. The reason I think investors should pay attention to this biotech company is because it is preparing to report expansion cohort data from the same study later in 2024. I think the release of the next set of data is better because it will involve a specific group. That is, two combinations of IMM-1-104 were administered to patients with PDAC, followed by three additional injections of the drug as monotherapy in patients with PDAC, RAS-mutant non-small cell lung cancer, and RAS-mutant melanoma. Another catalyst to watch is the dosing of the first patient in a Phase 1/2a trial using IMM-6-415 to treat patients with mutated RAS/RAF pathways.
I believe this is another important project to watch because it targets two MAPK pathway mutations and may ultimately outperform IMM-1-104. That remains to be seen, but it’s expected that the first patient treated with IMM-6-415 could happen any day in March 2024. Based on preclinical testing, there are high hopes for the drug candidate. In a head-to-head animal model study of RAF-mutant melanoma and colorectal cancer, results showed that the combination of IMM-6-414 and Braftovi was able to achieve deeper tumor regression compared with Mektovi + Braftovi. Whether this can be replicated in human clinical testing remains to be seen, but if such activity is ultimately observed, IMM-6-415 is another important drug in Immuneering’s pipeline to watch.
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