Immuneering Corporation (NASDAQ:IMRX) Q4 2022 Earnings Call Transcript

Immuneering Corporation (NASDAQ:IMRX) Q4 2022 Earnings Call Transcript March 6, 2023

Operator: Welcome to the Immuneering Fourth Quarter and Full Year 2022 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. Following management’s prepared remarks, we will hold a Q&A session. As a reminder, this call is being recorded today, Monday, March 6, 2023. I would now like to turn the conference over to Laurence Watts of Gilmartin Group. Please go ahead.

Laurence Watts: Thank you, operator. Joining us on the call today from Immuneering are Chief Executive Officer, Ben Zeskind; Chief Scientific Officer, Brett Hall; Chief Medical Officer, Scott Barrett; and Vice President of Finance and Treasurer; Mallory Morales. During this conference call management will make forward-looking statements, including statements relating to guidance and timing of data readouts for IMM-1-104 and IND submission of IMM-6-415. These forward-looking statements are based on the company’s current expectations and inherently involved significant risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.

Factors that could cause results to be different from these statements include factors the company described in the section titled risk factors on an annual report on Form 1-K filed with the SEC today, March 6, 2023. Immuneering undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events or changes and its expectations. With that, I will now turn the call over to Chief Executive Officer, Ben Zeskind. Ben?

Benjamin Zeskind: Thank you, Laurence. Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2022 financial results conference call. The first such call we are hosting in our company’s 15-year history. Let me start by assuring you that we do not plan to host an earnings call every single quarter, we will probably do them more than once every 15 years, though, maybe somewhere in between. Today, we have a lot to say, though, about our plan for the upcoming year, and about the timing of our ongoing clinical trials. Our goal is to create medicines for large populations of cancer patients. And we took one giant leap in that direction in 2022, as the first patient was dosed in our Phase 1/2a trial of IMM-1-104 for the treatment of RAS mutated solid tumors.

We are proud to be a clinical stage oncology company thanks to years of hard work by so many Immuneers, and we are looking forward to sharing updates as the trial proceeds. Before I cover our achievements in 2022 and recent events, let me first take a step back and give everyone context on our counterintuitive approach to drug development. It is our belief that the name of the game in cancer therapy is not how do you kill cancer cells? It’s how do you kill cancer cells with less risk to the healthy cells. It’s all about therapeutic index. And historically, that has been really hard, and that’s why cancer drugs are so commonly associated with such bad side effects, such poor tolerability. At Immuneering, we are developing what we believe is a fundamentally new way to achieve therapeutic index, a novel way to hit the tumor hard, while going easy on the healthy cells.

And we think it’ll enable us to develop treatments with the potential to benefit large numbers of patients globally with RAS-driven cancer. Most companies either go narrow by developing medicines that target specific individual RAS mutations such as KRAS-G12C, or they go abroad and hit wild type RAS in healthy cells, and they hope to find a dose that harms the tumor more than the patient. In other words, unfortunately, this approach frequently leads to high toxicity. They say no pain, no gain. We believe cancer patients deserve better. They deserve less pain, and more gain. We are working to rewrite the rules to develop therapies that are designed to help patients with any mutation in KRAS, NRAS or HRAS, and that aim to provide more durable effects with better tolerability.

Our approach utilizes a novel mechanism called deep cyclic inhibition, which is designed to maximize therapeutic activity, while providing improved tolerability and durability. We aim to do this by taking advantage of the fact that the cancer cells are always on. They need the MAP kinase pathway all the time, whereas healthy cells use the pathway more intermittently. And I’ll have more to say on that shortly. But first, we needed to figure out how to describe our approach and there really wasn’t an existing prefix or a suffix that works. The closest ones were multi and pan, and it’s not wrong to say we see pan-RAS activity preclinically. But pan is a prefix from the ancient Greek and it sounds like cookware, and it just doesn’t capture the excitement and the newness of what we’re trying to accomplish.

Importantly, both pan and multi tend to be associated with therapies that do not distinguish between the wild-type RAS in healthy cells, and the mutant RAS in cancer cells, which raises concerns about therapeutic index and long-term tolerability for those therapies. So we adopted a phrase that aptly describes this uniquely broad approach, and are fundamentally new way of achieving therapeutic index, and it’s universal-RAS. And I’m being a bit light hearted about the name, but let me assure you that we believe the potential for universal-RAS activity is incredibly serious and incredibly important to cancer patients and to their oncologist. The potential of our approach is supported by our preclinical data, and we are sharing some of our modeling data this week as the AACR targeting RAS conference.

As described in our poster presentation, we tested 132 different cancer cell line models in our proprietary humanized 3D tumor growth assays in our labs in San Diego, including 75 models with RAS mutations. We’re not saying that every single RAS-mutant model response, but 64 of the 75 models tested, or approximately 85% did respond. And at least one model displayed response to IMM-1-104 for each observed RAS mutation, regardless of the mutation position, or amino acid substitution. So this preclinical data suggests there’s no RAS mutation we know of that’s off limits to IMM-1-104. And for our clinical trial enrollment criteria, any solid tumor patients with any mutation in KRAS, NRAS or HRAS is eligible to be screened for our Phase 1 trial.

As a result of these broad inclusion criteria, and the robust preclinical data we have generated to date, we’re seeing great enthusiasm from our clinical investigators, and one indicator that is the fact that we dosed the first patient less than 2 months after receiving IND clearance. With enrollment ongoing, we are today providing guidance on when we could expect to report initial data readouts from the trial. Currently, we expect to share initial PK and safety data in mid-2023, initial pharmacodynamics and updated PK and safety data in the second half of 2023, the announcement of a recommended Phase 2 dose and additional safety data in mid-2024 with additional trial updates on a periodic basis. We believe human PK data is a particularly important milestone for IMM-1-104, because PK is such an important part of how IMM-1-104 achieved universal-RAS activity in preclinical studies.

I mentioned earlier that malignant cells depend on continuous signaling of the pathway, while the healthy cells can tolerate more interruptions. But one of the rules of targeted cancer therapy has been chronic pathway inhibition, which means if a pathway is locked on by a driver mutation, you must lock it off, or chronically ablated 24/7. And the problem with this approach is that healthy cells use the MAP kinase pathway too. We have this pathway for reasons other than for cancer to hijack it. But the conventional wisdom is you make drugs with long-half lives, and they’re dosed in such a way as to always maintain target occupancy to maintain a drug trial. And it’s intuitive right to shut down the pathway 24/7. But if we keep doing the intuitive thing, we’ll keep getting the same result.

The old no pain, no gain philosophy. So we decided to rewrite the rules in the design of IMM-1-104. IMM-1-104 began with a counterintuitive observation from our disease canceling technology platform, that earlier time point did a better job of reversing disease at the transcriptomic level than later one. And that helps us to realize that you may not actually have to shut down the pathway 24/7, you just have to prevent it from being on 24/7. So we designed IMM-1-104 to pulse the tumor with a manyfold higher free fraction CMAX, or in plain English, a very high peak drug exposure. Yet we also have a short half life in order to enable sufficient inhibition of the pathway, while still achieving a near-zero drug trough to allow the drug to clear the system and reset the pathway each day, a process we call deep cyclic inhibition.

So our approach aims for every day to be a drug holiday for the healthy cells, and every day to be judgment day for the tumor. IMM-1-104 has demonstrated preclinical activity with strong tumor growth inhibition in each animal model we have tested, including KRAS-G12C, KRAS-G12F, KRAS-G12D, KRAS-G12V, as well as NRAS mutant animal models. And as I said earlier, we can now also say approximately 85% of the 75 RAS-mutant models we tested in our humanized 3D tumor growth assays responded to IMM-1-104. This positions IMM-1-104 to be the first and only MAP kinase pathway inhibitor with the potential for universal-RAS activity. Achieving that in humans depends on good tolerability with a short half life and a high CMAX. And that’s why the PK and safety data we expect to share in mid-2023 is so important.

If IMM-1-104 achieves in humans, and things like what we have observed preclinically, I believe, it has the potential to be truly game changing for large numbers of cancer patients in the near-term. This is also a serious responsibility, and it requires our full focus and our undivided attention. So we have made a decision to suspend our early stage neuroscience program and focus ongoing development activities solely in oncology. Suspension of our neuroscience program, as well as other non-core adjustments, extends our projected cash runway by one quarter into the fourth quarter of 2024, which is reflected in the updated runway guidance we have provided today. The oncology pipeline, which is now our sole focus, started less than 5 years ago as a research project by an extraordinary consultant named Brett Hall, who subsequently became our Chief Scientific Officer.

Let me now turn the call over to Brett to say a few words about our unique approach and our latest data.

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Brett Hall: Thank you, Ben. I’d like to start off by highlighting a key factor that we believe truly differentiates Immuneering from other biotech companies in the oncology space. Our aim is to develop drugs for larger patient population using translational bioinformatics and humanized 3D tumor growth assays. We believe this approach enables us to design drug candidates with distinguishing features that select for a favorable activity and toxicity profile. One example of this application is the pharmacokinetics and target gate engagement of our lead asset IMM-1-104. IMM-1-104 was designed to have a short half life that can lead to many full higher drug free fraction, while still achieving near-zero drug trial. We believe this profile enables deep cyclic pathway inhibition.

We also designed IMM-1-104 to overcome resistance from CRAF-bypass. We said that we project approximately a 2-hour half-life in humans, which is much shorter when compared to other MEK inhibitors in the space that have up to multi-day half-lives. Our preclinical data suggests potential for robust activity in pancreatic cancer, melanoma, non-small cell lung cancer, colorectal cancer, and other solid tumors with RAS-mutant disease. Using humanized 3D tumor growth assays followed by select in vivo studies, we have identified NRAS-driven melanoma in KRAS-driven pancreatic cancer has two potential high priority indications that we believe are both largely unaddressed and may be broadly sensitive to IMM-1-104. But as Ben mentioned earlier, we have reported on 132 tumor models that span over a dozen tumor types with various mutational profiles.

And we observed brought activity in 64 out of the 75 models, or approximately 85% that display mutant RAS. And there was no specific RAS mutation where we didn’t see potential activity. Additionally, our translational research team is further evaluating KRAS mutant lung cancer and KRAS mutant colorectal cancer to identify biomarkers that enrich for highest potential for monotherapy response. In 2022, Immuneering presented 3 abstracts on 2 programs: 2 at the American Society of Clinical Oncology, or ASCO, in May of 2022; and 1 at the SITC Annual Meeting in November of 2022. The first abstract, a head-to-head comparison of IMM-1-104 versus sotorasib or adagrasib in KRAS mutant pancreatic cancer demonstrated lack of tumor growth inhibition by both sotorasib and adagrasib in the KRAS-G12V mutant Capan-2 pancreatic ductal adenocarcinoma tumor model.

In contrast, IMM-1-104 observed tumor growth inhibitions of 49% to 84% across all doses and schedules tested consistent with other IMM-1-104 in vivo studies, median body weight was no more than 3% to 6% at the top doses. The second abstract we presented at ASCO found KRAS mutant pancreatic cancer and NRAS mutant melanoma were the most broadly sensitive to IMM-1-104 in patient aligned 3D human tumor growth assays, and thus are included among the expected target indications for Immuneering Phase 1/2a clinical trial. Finally, the third abstract presented at SITC highlighted the preclinical activity of our second pipeline asset, IMM-6-415 as a single agent, as well as a combination therapy with checkpoint inhibitors in RAS-mutant colorectal cancer and non-small cell lung cancer models driven by diverse MAP kinase pathway mutation.

IMM-6-415, in combination with immuno-oncology agents may have the potential to overcome resistance in the MAP kinase pathway, and to provide deeper and more durable responses. We expect to file the IND with the FDA for IMM-6-415 in the fourth quarter of 2023. As Ben mentioned, for IMM-1-104, we expect to share initial Phase 1 pharmacokinetic and safety data in mid-2023. With that, I’ll turn the call over to Scott to share an update on our Phase 1 clinical trial program.

Benjamin Zeskind: Thank you, Brett. Just before you do that, if I could just say that Scott joined our team in 2019, and at the time, everyone said, why do you need a Chief Medical Officer, when you’re a few years from the clinic? And we said 2 reasons. We want a clinicians’ perspective in our preclinical development, and so we can lay all the groundwork to really hit the ground running in Phase 1. And I’m really proud of what a great team Scott has built and the great job they’ve done getting our trial up and running. So with that, over to you, Scott.

Scott Barrett: Thank you, Brett and Ben. I’m delighted about the progress that we’re making in our first in human clinical trial, evaluating IMM-1-104 in a Phase 1/2a open-label study, designed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy. IMM-1-104 is administered as a once-daily oral monotherapy for adult cancer patients with RAS-mutated solid tumors in an advanced setting and/or trial requires that they’ve already failed at least one line of systemic standard-of-care treatment. This Phase 1 open-label study utilizes a Bayesian mTPI-2 escalation design for IMM-1-104. This includes a dose escalation phase and a dose evaluation phase in order to evaluate safety and establish an optimized Recommended Phase 2 Dose or RP2D candidate in mid-2024.

This is expected to segue into a Phase 2a dose expansion and approximately 160 total patients in 4 parallel cohorts, which independently evaluate monotherapy treatment effects in RAS-mutated melanoma, pancreatic cancer, non-small cell lung cancer and colorectal cancer. The primary endpoint of the Phase 2 trial will be response rate that’s defined by objective radiographic response assessment, measured by radiographic imaging changes from pre-treatment baseline. This is first observed for each patient at 2 months, and continues every 8 weeks thereafter for patients receiving benefit from study drug for up to 48 weeks of treatment. Overall, we’ve received great enthusiasm from our investigators across 5 clinical sites in the United States, who are all eager to enroll patients as soon as possible.

In fact, we have a robust waitlist for patients. Our Phase 1 program is now open to all comers with evidence of any RAS mutation, including KRAS, NRAS and HRAS as IMM-1-104 has been designed to be broadly active in tumors addicted to MAP kinase pathway signaling. In November 2022, we successfully dosed our first patients in the trial. For the time being, that’s all we’ve disclosed, but I expect that much more to say in the coming months as we begin to share data from the trial has been as laid out in today’s guidance. So with that, I’ll turn the call over to Mallory to cover our fourth quarter and full year financial.

Mallory Morales: Thank you, Scott. In addition to the financial results summarized in our press release we issued earlier today, I will share some key financial highlights on this call. You can also find additional information in our Form 10-K that was also issued earlier today. As of December 31, 2022, our cash, cash equivalents and marketable securities were $105.5 million, compared with $150.2 million as of December 31, 2021. Operating expenses for the fourth quarter of 2022 were $14 million compared with $11.1 million for the fourth quarter of 2021. Full year 2022 operating expenses were $51.9 million, compared to $34.8 million for full year 2021. The increase in total operating expenses in 2022 was primarily due to the advancement of IMM-1-104 through IND and into our Phase 1/2a clinical trial, as well as employee-related costs due to increase headcount.

Net loss attributable to common stockholders was $13.2 million for the quarter ended December 31, 2022 compared to $10.8 million for the quarter ended December 31, 2021. Net loss attributable to common stockholders for full year 2022 was $50.5 million, compared to $33.5 million for the full year 2021. As of February 27, 2023, we have 26,436,109 shares outstanding. In terms of our cash runway, management expects our cash, cash equivalents and marketable securities to be sufficient to fund operations into the fourth quarter of 2024. That concludes the financial update. And I’ll now turn the call back over to Ben.

Benjamin Zeskind: Thank you, Mallory. Mallory and her team are doing a phenomenal job, and we’re very lucky to have them. Let me wrap things up by saying that nobody should be dying of cancer in 2023. I’ll say that again, nobody should be dying of cancer in 2023. Cancer doesn’t work by magic, not some paranormal force. It operates by a set of biological mechanisms that are actually well understood. It’s just really good at hiding among the healthy cells, and it essentially hijacked the person’s body and take them hostage. The challenge is, how do you kill the hijackers with less risk to the hostages? How do you achieve a therapeutic index? And today, companies have either gone narrow by targeting a single mutation such as KRAS-G12C, or they’ve gone broad, but in a way that hits wild-type RAS in healthy cells.

At Immuneering, we believe it’s time to go broad. We believe that deep cyclic inhibition represents a fundamentally new way of focusing the activity against the malignant cells of taking out the hijackers with less risk to the hostages. It’s time to make medicine with the potential for universal-RAS activity. In the past 24 hours, we’ve released new preclinical data we’ll be showing an AACR targeting RAS this week, which is a curative force in demonstrating the universal RAS activity of IMM-1-104 in preclinical models, and our clinical trials moving forward rapidly, because our enrollment criteria are truly universal-RAS, and soon it will be time to share data showing how that deep cyclic inhibition is playing out in humans. We believe 2023 is shaping up to be Immuneering breakout year, and we aspire to make 2023 a year that marks an important turning point in the battle against cancer.

With that, I’d like to thank all of our patients, clinical investigators, and stakeholders for their continued support of Immuneering. And I look forward to updating you all in the coming months on our progress towards our goal of a universal-RAS therapy for cancer patients. I will now open the call up for questions. Operator?

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Q&A Session

Operator: Our first question comes from the line of Swapnil Malekar from Piper Sandler.

Swapnil Malekar: Thank you for taking my questions. I have a couple of them. First one is can you comment on how many patients have been dosed in the 104 trials so far? And what is the extent of the data that will be presented in the mid-2023 update?

Benjamin Zeskind: Hey, Swapnil, thanks for the question. We’re really pleased with the progress of the trial. And, I think we provided very detailed guidance today, probably more granular than many companies often do. And, we’re really excited to share the initial PK and safety data in mid-2023 and the rest of the data as we’ve outlined.

Swapnil Malekar: Got it. Okay. And then I have one follow-up. So regarding the AACR poster tomorrow, what additional data does the poster include that has not been previously presented? And from this new preclinical study, are you seeing any specific trends related to tumor types or mutation status that could inform your ongoing clinical trial in terms of patient selection? Thank you for taking my questions.

Benjamin Zeskind: Sure. Thanks, Swapnil. I’ll hand it over to Brett in a second to see if there’s anything he wants to add. But, the poster is available already on our website. And, I think, one of the key takeaways from the poster is really the universal-RAS activity that we’re seeing the fact that about 85% of the cell lines that we tested with RAS mutations in the humanized 3D tumor growth assay are really responsive to IMM-1-104. And there’s really no mutation that’s not responsive, right? Every mutation has at least one model within, that’s responsive. But let me see if there’s anything Brett would like to add there.

Brett Hall: Thanks, Ben. And, hey, Swapnil. Yeah, I would add that the poster is really a deep-dive into a broad panel of tumor models that we’ve evaluated that have RAS and other MAP kinase pathway and non-MAP kinase pathway driven mutations. And it really is a deep-look or a deep-dive into our core platform are humanized 3D tumor growth assay platform that we’ve used and have vetted additionally with in vivo studies on the back end. So including those that we’ve discussed before like MIA PaCa, A549, SK-MEL-2, and others, have all basically been vetted both in the 3D-TGA as well as in vivo.

Benjamin Zeskind: So it just really €“ thank you, Brett. Yeah. So Swapnil, it’s just really broaden the scope of models that we’ve released publicly. And I think all of this contributes to the really the universal-RAS activity that we’ve seen preclinically and, frankly, supports the enrollment criteria for our clinical trial, which is truly open to patients with any mutation in KRAS, NRAS or HRAS. So, with that, thanks for your question, Swapnil.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Michael Yee from Jefferies.

Unidentified Analyst: Hi, guys, this is Tina on from Mike, I just had a couple of quick questions, and congrats again on the progress. What doses are you using right now to dose escalate? And are the low doses that you’re starting at therapeutic at all, where we could potentially see responses in that mid-2023, or second half update? I know, you just only said that you would be seeing or sharing PK/PD and safety data, but just wondering if there is a potential for efficacy data or those response that I would see there. And, I guess, another thing, if you could just share some more color on the PD modeling that you are planning to share in the second half? What does that entail? And what type of biomarkers that you’re really looking to share there? Thank you.