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Immuneering Corporation (NASDAQ:IMRX) just reported positive results from the phase 1 portion of its phase 1/2 study using IMM-1-104 for the treatment of patients with RAS-mutant solid tumors. Specifically, a huge chunk of these patients had pancreatic cancer followed by other solid tumors with this mutated expression. Initial data showed favorable safety and anti-tumor activity, along with the finding of a good recommended phase 2 dose [RP2D] to move on with. Even though this catalyst has passed that doesn’t mean that investors can’t yet again benefit from another one to come later on relating to this program. How so? That’s because the goal of this initial study was just to look at safety, PK, PD and some anti-tumor effect of IMM-1-104. Plus, it was a basket study. The goal of this biotech is to release additional results from the expanded portion of this phase 1/2a study using this drug in 5 other cohort arms to be initiated in March of 2024.
Such data is expected late this year and if positive, could yield substantial gains for investors. The first three cohort arms are going to deal with using IMM-1-104 as a monotherapy to treat specific RAS-mutant solid tumors and then the other two cohorts are going to include the use of this drug in combination with other drugs to treat patients with RAS-mutant non-small cell lung cancer [NSCLC]. The thing is that IMM-1-104 is only one drug in the pipeline to be used as once-daily dosing targeting RAS-mutant patient. However, there is another drug in the pipeline with greater potential, which is IMM-6-415. What this brings to the table is to target both RAS and RAF mutant solid tumors and being able to do so with BID [twice-daily] dosing.
An analyst at TD Cowen downgraded Immuneering to Market Perform rating, citing that the monotherapy data was not differentiated compared to other RAS inhibitors in this space. My take on this is that they still have a “Market Perform” rating and still state that it achieved an excellent safety profile. Thus, it can still do well in terms of using IMM-1-104 in combinations. As I will show below, it is combining IMM-1-104 together with mFOLFIRINOX and gemcitabine/paclitaxel to target 1st-line Pancreatic ductal adenocarcinoma [PDAC] patients. Despite this downgrade, I still believe that this company has proven its mechanism of action in targeting the MAPK pathway for treating tumors. With additional data of IMM-1-104 in RAS-mutant solid tumor patients, plus additional data to be released from 5 other cohorts in 2024, I believe that investors could benefit from any potential gains made.
IMM-1-104 For The Treatment Of Patients With RAS-Mutant Solid Tumors
As I stated above, Immuneering just released results from the phase 1 portion of the phase 1/2a study, using IMM-1-104 for the treatment of patients with RAS-mutant solid tumors. This was with respect to achieving several initial measures such as: Pharmacokinetic [PK], Pharmacodynamic [PD], circulating tumor DNA [ctDNA] and initial anti-tumor activity. This particular study recruited eight different solid tumor types with RAS-mutations. However, a huge chunk of the population [60%] had pancreatic cancer. As I will show below, this population is important because two of the five phase 1/2a expansion cohorts are targeting RAS-mutant non-small cell lung cancer [NSCLC] patients. What was revealed is that this study did not incorporate clinical activity as an endpoint, but that doesn’t matter, because what was revealed was pretty good. For starters, over 50% of the patients treated with either 320 mg or 240 mg QD dosing of IMM-1-104 had achieved tumor lesion regression. Best individual regression of tumor achieved was -35.7% at 320 mg of drug targeting a 2nd-line RAS-mutant solid tumor patient. My belief is that this drug has a good chance at making a huge impact in treating RAS-mutant solid tumors. Not only because of the initial efficacy that was achieved, but also due to the fact that the drug achieved the ability to suppress RAS alterations. It was noted that there was full suppression [100%] of acquired RAS alterations when ctDNA was evaluated. Why is this finding important? For starters, it shows that universal RAS MAPK pathway targeting was achieved. Thus, this leads to the second positive item out of this outcome, which is the ability to suppress resistance mechanisms. A lot of RAS-mutant solid tumor patients that are treated, acquire several MAPK pathway resistance mechanism along the way. With IMM-1-104 being able to suppresses such acquired RAS alterations, it could theoretically provide for a more substantial clinical outcome.
This was a pretty good outcome for the phase 1 portion of the phase 1/2a study using IMM-1-104 for the treatment of patients with RAS-mutant solid tumors. Especially, when you consider that 80% of them with metastatic disease never responded to any prior treatment either. With a large chunk of patients having pancreatic cancer, this might be a huge focus for the company. The first reason why is that the FDA gave IMM-1-104 Fast Track Designation for the treatment of this specific patient population. The second reason is because as I stated above, two out of the five cohorts are going to zero in on targeting patients with pancreatic ductal adenocarcinoma [PDAC]. The phase 2a combination expansion port of the trial is evaluating 60 1st-line PDAC patients in the 1st line setting as follows:
- IMM-1-104 + mFOLFIRINOX [30 patients]
- IMM-1-104 + gemcitabine and nab-paclitaxel [30 patients]
the other three cohorts being deployed are to use IMM-1-104 as a monotherapy for PDAC, RAS-mutant melanoma and RAS-mutant NSCLC. There are two catalysts to look forward to with respect this program. The first of which would be the release of phase 1/2a expansion cohort data of IMM-1-104 for RAS-mutant solid tumors. The goal is to use the RP2D achieved and deploy it in both the monotherapy and combination therapy arms shown above and generate additional data. Such data is expected to be released later in 2024 and I believe that positive data released could cause the stock price to trade higher. A smaller catalyst might be presentation of the recently released data from the phase 1 portion of the phase 1/2a study using this drug to treat several of these RAS-mutant solid tumor patients. This is also expected during the same time period as well.
Financials
According to the 10-K SEC Filing, Immuneering had cash, cash equivalents and marketable securities of $85.7 million as of December 31 of 2023. The reason for the cash on hand is because of its ability to raise $30 million in an underwritten public offering. That is when it sold 2,727,273 shares of its Class A common stock at an offering price of $11 per share. The aggregate net proceeds generated from this public offering, after deducting expenses, was $28.2 million. This biotech is in good shape for quite some time, especially when you consider the projection that it has provided. It believes that it has enough cash on hand to fund its operations into the 2nd half of 2025. The only way I could see this biotech enacting another cash raising event, is if the positive data to be released later on this year from the phase 2 portion of the phase 1/2a study of IMM-1-104, causes the stock price to trade higher. Then, I believe management would take advantage of such a rise and raise cash earlier than anticipated.
Risks To Business
There are several risks that investors should be aware of before investing in Immuneering Corporation. The first risk to consider would be with respect the advancement of IMM-1-104 for the treatment of patients with RAS-mutant solid tumors. Even though initial data from the phase 1 portion of the phase 1/2a study achieved initial positive safety and anti-tumor activity, there is no guarantee that the same will happen in the 5 expansion cohorts being evaluated. In addition, the goal of the company is to see if the combination of IMM-1-104 with either one of the two typical front-line therapies for patients with pancreatic cancer achieve superior efficacy data. There is no assurance that adding IMM-1-104 with either mFOLFIRINOX or gemcitabine/nab-paclitaxel will yield desired results in targeting PDAC patients.
The second risk to consider would be with respect to the advancement of IMM-6-415 for the treatment of patients with RAS/RAF mutant solid tumors. It believed that this drug can be used to target both of these MAPK pathways effectively, but there is no assurance that it will do so. What this clinical candidate drug deploys is a shorter-half life and thus can be dosed twice daily. This alternate approach might be feasible to be able to dose patients twice-daily with IMM-6-415, but there is no way of knowing whether or not any major tolerability issues will arise because of this. This is also expected to be developed in combination with other drugs, in hopes of helping to improve clinical outcomes in the targeting of RAS/RAF mutant solid tumors. While the drug may eventually prove to effective in treating such patients as a monotherapy, there is no guarantee that combinations will ultimately be able to yield superior data.
A third risk to consider would be with respect to competitors in this space. I see great potential here based on the initial data that this company has released thus far, mainly with the ability for 100% of patients to suppress RAS acquired alterations. This is critical, because the last thing that a patient needs is for the cancer itself to develop resistance mechanisms as treatment is ongoing. The first competitor of which is Bristol-Myers Squibb (BMY) with Krazati, which was approved by the FDA 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 this RAS-mutant pathway space would be Amgen (AMGN) with Lumakras, which was also approved by the FDA for the treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC following 1st-line therapy. Although, these biotechs have a focus on targeting KRAS G12C as part of the RAS mutation pathway.
Conclusion
Immuneering Corporation has been able to establish initial anti-tumor activity in being able to target patients with RAS mutations with its IMM-1-104 drug in the phase 1 portion of the phase 1/2a study. Why I believe investors should keep an eye on this biotech is because it is gearing up to report expansion cohort data later on in 2024 from this very same study. I think it will be better with the release of the next set of data because it is going to entail specific cohorts. That is, two combinations of IMM-1-104 targeting patients with PDAC and then three other shots on goal using this drug as a monotherapy for the treatment of patients with PDAC, RAS-mutant NSCLC and RAS-mutant melanoma respectively. Another catalyst to keep an eye on would be the dosing of the first patient in the phase 1/2a trial using IMM-6-415 for the treatment of patients with RAS/RAF mutant pathway.
I believe that this is another important program to watch, because it targets two MAPK pathway mutations and may end up being superior to that of IMM-1-104. This remains to be seen, but the first patient is expected to be dosed with IMM-6-415 could happen any day now in March of 2024. There is high hopes for this candidate based on preclinical testing. In a head-to-head animal model study targeting RAF mutant melanoma and colorectal cancer, it was shown that IMM-6-414 in combination with Braftovi was able to achieved deeper regression of tumor compared to Mektovi + Braftovi. This remains to be seen if it can be replicated in human clinical testing, but if such activity is ultimately observed, then IMM-6-415 is another important drug to watch in Immuneering’s pipeline.
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