Welcome to the Immuneering Conference call to discuss a positive data update from the three pancreatic cancer arms of the company's ongoing phase IIA trial of IMM-1-104. At this time, all participants are in listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ensure that we will have ample time to address everyone's questions, we would ask each person to limit themselves to one question and one follow-up. As a reminder, this call is being recorded today, Tuesday, January 7, 2025. I would now like to turn the conference call over to Laurence Watts of New Street Investor Relations. Please go ahead.
Thank you, Operator. Joining us on the call today from Immuneering are Chief Executive Officer Ben Zeskind, Chief Scientific Officer Brett Hall, Chief Accounting Officer and Treasurer Mallory Morales, and Peter Brakewood, our Chief Business Officer, as well as Dr. Alan Sandler, a consultant to the company. During this call, management will make forward-looking statements, including statements related to its phase IIA trial of IMM-1-104, as well as the timing of additional data from the study and the company's development plans. Our actual results on 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 these results to be different from the statements include factors the company describes in our annual report on Form 10-K and our quarterly reports on Form 10-Q.
Immuneering undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. With that, I will turn the call over to Ben Zeskind, Chief Executive Officer of Immuneering. Ben.
Thank you, Laurence. Good morning, everyone, and thank you for joining our conference call. We're excited to share with you a positive data update from the three pancreatic cancer arms of our ongoing phase IIA trial of IMM-1-104. Our goal as a company is to help cancer patients live longer and feel better. Too many patients have to choose one or the other, and it shouldn't be that way. I believe today's update demonstrates that we have made substantial progress towards this goal. During today's presentation, I will be making forward-looking statements. Please read our disclosures on slide two for more information regarding these. All data I will be discussing today is as of the December 5th cutoff date, unless otherwise noted. Since we want to help patients live longer, we decided to start with a target that has already been proven to do exactly that: MEK.
MEK is part of the RAS/RAF/MEK pathway that drives many different cancers, and when a registered MEK inhibitor is added in combination with a RAF inhibitor for patients with BRAF mutant melanoma, the MEK inhibitor adds about six months of survival when compared to the RAF inhibitor alone. So that's a great combination for patients, and it's also good business. If you look at sales of that combination and add in the contributions of the three other currently approved MEK inhibitors, it's about $2.4 billion in net sales in 2023. But the currently approved MEK inhibitors aren't perfect. They're limited mainly to patients with BRAF mutant tumors, and there's plenty of room for improvement on tolerability. We set out to build a better MEK inhibitor, one that could help more patients live longer and feel better, and to do that, we're pursuing two specific goals.
Our first goal is to expand the indications beyond BRAF to also include the large number of patients with tumors driven by RAS and other mutations in this pathway. Our second goal is to improve the tolerability, and that's something that could benefit both the patients with BRAF mutant cancers who already receive MEK inhibitors as well as patients with cancers driven by RAS and other mutations in the pathway who do not have that option. Based on these goals, we developed a new MEK inhibitor called IMM-1-104 with a very different set of characteristics. Today, we're sharing a substantial update of clinical data that supports the benefits of this approach. Let's start with our goal of expanding indications beyond BRAF to RAS-driven cancers and beyond. Over 90% of pancreatic cancer is RAS-mutated, and the numbers even higher when you include other mutations that activate this pathway.
We are profoundly excited to report that in first-line pancreatic cancer patients who receive IMM-1-104 in combination with modified gemcitabine nab-paclitaxel, we continue to see excellent activity with a 43% overall response rate and an 86% disease control rate, both of which compare very favorably to historical benchmarks. These response rates include a confirmed complete response, which is extremely rare in pancreatic cancer. For anyone in oncology, when a site calls and tells you they can't find the cancer anymore, that's an emotional moment, and we can only imagine what it feels like for a patient to receive that news after one scan, let alone multiple scans. Today, we're also sharing initial data from the other two pancreatic cancer arms of our trial. In the IMM-1-104 plus modified FOLFIRINOX arm in first-line patients, we have a confirmed partial response with a 100% reduction.
That's a second example of target lesions completely disappearing in a patient treated with 104, this time in a patient with a very common KRAS G12D mutation. In monotherapy in second-line pancreatic cancer patients, we have a confirmed partial response with a 67% reduction. Based on the strength of these data, we've started planning a pivotal trial of IMM-1-104 plus modified gemcitabine nab-paclitaxel, and we also plan to initiate additional phase IIA combination arms this year. In terms of our second goal of improving tolerability, today we're sharing new safety data where we continue to see a highly differentiated tolerability profile of 104, both alone and in combination with modified gemcitabine nab-paclitaxel. In total, we've now shared safety data from 96 patients.
We believe there's a broad potential of IMM-1-104 to enable new combinations and replace existing MEK inhibitors in established combinations for patients with a wide variety of tumors driven by BRAF, RAS, or other mutations in this pathway. 104 is by far the best tolerated MEK inhibitor we're aware of. Just as one example of that, we have a patient from the phase I portion of our trial who has now been on treatment for 11 months and who has gained nearly 20 pounds. This patient is also showing improved quality of life. This is a third-line pancreatic cancer patient who had progressive disease on two lines of prior chemotherapies, but now has stable disease with a 25% reduction in target lesions with 104. Not only is this really encouraging progress for that patient, but strong evidence of the durability, activity, and tolerability of 104.
So how is 104 able to yield such different results from prior MEK inhibitors? It's oral, and patients take it once daily every day. The chemistry of 104 causes the concentration of the drug to quickly hit a higher maximum or Cmax than other MEK inhibitors, and then through a shorter half-life, the concentration quickly drops to a lower minimum or trough than other MEK inhibitors. 104 also prevents MEK activation by RAF, something no approved MEK inhibitor does. So basically, 104 is designed to hit the pathway harder or more deeply than other MEK inhibitors, but in a cyclic way that's designed to improve tolerability. We call it Deep Cyclic Inhibition, and it's the key to how we are able to achieve the kind of clinical results we are sharing today.
So far, the first five arms of our ongoing phase IIA trial are focused on the goal of expanding beyond the indications where MEK inhibitors are already approved into pancreatic cancer as well as RAS mutant melanoma and lung cancer. Starting with our first arm, using IMM-1-104 plus modified gemcitabine nab-paclitaxel in first-line pancreatic cancer, here you can see the historical benchmark ORR from gemcitabine nab-paclitaxel is only 23%, which really highlights the unmet need in this area. And we've received some very encouraging FDA designations for IMM-1-104, including orphan drug designation, fast track in first-line and second-line pancreatic cancer, as well as fast track in NRAS mutant melanoma. Overall, our trial has seen a huge uptick in enrollment over the past few months, with over 75 pancreatic cancer patients enrolled across all three arms as of the data cutoff date.
Pancreatic cancer has an extremely low five-year survival rate, and there are few treatment options, and those options aren't very good, and hence first-line pancreatic cancer patients face a difficult choice. They essentially live longer or feel better. It's an or, not an and, for the two categories of therapy that are currently most commonly used in the first line. FOLFIRINOX and related treatments do a bit better than gemcitabine nab-paclitaxel on efficacy, but they're worse on tolerability. Whereas for gemcitabine nab-paclitaxel and related treatments, you see a bit of a decrease in efficacy, but an improvement in tolerability. With 104 plus modified gemcitabine nab-paclitaxel, we aim to give patients a better option. They shouldn't have to choose between activity and tolerability. They should be able to live longer and feel better, and that's our goal.
I believe the data I'm going to share with you today shows we're making substantial progress toward that goal. To put some numbers behind the symbols on the previous page, these are the overall response rate, disease control rate, complete response rate, and survival data for the two current standards of care. Either way, it's tough. For gemcitabine nab-paclitaxel, you're looking at a 23% ORR, but some improvement in the neutropenia, the fatigue, and the diarrhea compared to FOLFIRINOX. Again, our goal is to give patients a better option. Today, I'm delighted to share that we have a 43% overall response rate for patients responding to IMM-1-104 plus modified gemcitabine nab-paclitaxel, including a complete response with 100% regression. I'll note that both of the partial responses are confirmed across multiple scans, as is the complete response.
The other thing we find very encouraging is that all the patients shown in the waterfall plot have reductions in their sum of longest diameters. Given the historical benchmark of about 50% disease control rate, you would expect a left half of this waterfall plot, if you will, and we're just not seeing that here, which is very, very, very encouraging. We believe this shows IMM-1-104's potential in combination to really offer better efficacy in that first-line setting. It also has the potential to offer better tolerability. This table shows the treatment emergent adverse events for the combination that are observed in at least 10% of patients. You can see no Grade 4 events. You can count on one hand the number of Grade 3s in any category and also see a modest number of Grade 2s and Grade 1s.
Importantly, there were no serious adverse events related to IMM-1-104, and to state the obvious, some of these specific adverse events are associated with the gemcitabine nab-paclitaxel part of the combination. With regard to Grade 3 or Grade 4 neutropenia, we're only seeing 10%, no Grade 3 to 4 fatigue, and 5% diarrhea. So when you combine that excellent safety profile with the 43% ORR, 86% disease control rate, and 14% complete response rate that we're reporting together, altogether, what we're reporting today compares very favorably to the historical precedent for the current first-line standard of care agents. Our goal is to give patients a better option where they can have better efficacy and better safety, and as a result, they can live longer and feel better. And we believe if these data trends continue, we have a clear path to registration with this combination.
We have started planning for a pivotal trial, which I will talk about more in a few minutes. And we're not the only ones. Our KOLs feel the same way. The quote on this page is from Tony Saab, who's an investigator for the trial and, of course, a legend in the pancreatic cancer space at the Mayo Clinic. This is what he had to say about the data: "Very promising.
If these trends continue, this combination may provide improved efficacy and tolerability versus gemcitabine nab-paclitaxel in first-line pancreatic cancer." And he also speaks to the broader potential for IMM-1-104 by saying, "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." We also have three other excellent members of our pancreatic cancer SAB who are similarly enthusiastic about IMM-1-104 and particularly this combination for pancreatic cancer. Let's move on to the second arm now because we're also very encouraged by what we're seeing there in first-line patients in combination with modified FOLFIRINOX. In our combination of IMM-1-104 with modified FOLFIRINOX, we're seeing encouraging initial data, including a 100% reduction. And the only reason that response is designated a partial response and not a complete response is that there is one lymph node that remains.
We're also very encouraged by the CA19-9 data for that patient, which is a blood-based biomarker of pancreatic cancer progression, which has dropped dramatically, and that patient remains on treatment. We find it very encouraging that all of these evaluable patients have their lesions shrinking. Specifically, we think the 100% reduction we're seeing in this combination with modified FOLFIRINOX helps to corroborate the complete response that we saw in the combination arm with modified gemcitabine nab-paclitaxel. Turning to the third arm in our update, let's look at IMM-1-104 as monotherapy in second-line pancreatic cancer. Now, here the benchmark for gemcitabine is 3% in second-line pancreatic cancer patients previously treated with FOLFIRINOX, like most of our second-line patients, and in light of that, and for many other reasons, we're very encouraged by what we're seeing here.
Currently, we're seeing a 5% overall response rate, including one deep regression, which is a confirmed partial response with a 67% SLD reduction and a disease control rate of 52%. We're very encouraged that so many of the patients have shrinking lesions on IMM-1-104 monotherapy and are continuing on treatment across a variety of different RAS mutations. In summary, we're extremely pleased by this initial data in terms of activity, but also in terms of tolerability, which I will now turn to. We have 21 patients' worth of tolerability data in this arm. Note that this table shows the treatment-related adverse events observed in at least 10% of patients. Put simply, IMM-1-104 is very well tolerated. There are no Grade 3 or 4 events in the table, one or two Grade 2s in each category, and then a few grade 1s.
What I believe we're looking at then is highly differentiated tolerability relative to anything that's been seen before for a MEK inhibitor, and that therefore sets up IMM-1-104 as a highly suitable candidate for both monotherapy and combination therapy. Given what we're seeing so far and given that suitability for combination therapy, we're now planning three additional arms for our phase IIA trial. This year, we plan to initiate an arm treating patients with IMM-1-104 plus a RAF inhibitor in BRAF mutant melanoma, similar to that approved combination that I referenced earlier, as well as two other combination arms in melanoma and lung cancer respectively, where we plan to utilize IMM-1-104 in combination with an anti-PD-1. Importantly, we are also receiving inbound requests for investigator-initiated trials. Investigators are hearing that there's finally a MEK inhibitor that's well tolerated and have come to us with ideas to further expand the impact.
As I mentioned earlier, based on the success we've seen thus far in the combination of IMM-1-104 with modified gemcitabine nab-paclitaxel in the first-line setting, we are planning for a prospective global phase III trial with patients randomized between IMM-1-104 plus modified gemcitabine nab-paclitaxel and the standard of care gemcitabine nab-paclitaxel in a first-line setting, with typical endpoints for a pivotal oncology trial. Of course, this is all subject to change and based on the ongoing phase IIA results and subsequent regulatory feedback, but it's important to note that if trends continue, we believe we have a clear path forward to registration for this combination.
So to wrap things up, our goal of expanding the indications for MEK inhibitor use continues, strengthened by the promising results we've shown you today, which have included responses across all three pancreatic arms and a highly favorable 43% ORR and 86% DCR in our combination with modified gemcitabine nab-paclitaxel. Looking to the year ahead, we expect to share additional phase IIA data in the second quarter, which should provide further guidance for our prospective pivotal trial, the planning for which is underway. In addition, we plan to initiate three additional phase IIA combination arms during the year. In terms of improving the tolerability profile for treatments where MEK inhibitors are already in use, we're delighted to have amassed a safety database for IMM-1-104, both alone and in combination, of 96 patients.
This excellent tolerability profile that is the best any of us have ever seen speaks to the broad potential of IMM-1-104 to be combined with many BRAF and RAS mutant cancers, representing significant upside for shareholders in terms of the prospective unmet needs that IMM-1-104 could address. As a reminder, MEK inhibitors are already a very impactful class of therapies, helping patients live longer and driving $2.4 billion in sales. We believe the clinical data we've shared today shows IMM-1-104's potential to do much better. Or, as one of our clinical investigators asked, "Is this the MEK inhibitor we've been waiting for?" and with that, we're happy to take questions. Operator.
Thank you. As a reminder, if you'd like to ask a question, please press star and the number one on your telephone keypad.
We'd also like to remind you to please kindly limit yourself to one question and one follow-up. We will pause for just a moment to compile a list. Thank you. And with the first question, that question comes from the line of Jay Olsen from Oppenheimer. Your line is open.
Oh, hey. Congrats on these really encouraging results, and thank you for providing this update. Can you talk about the number of patients you're planning to enroll in the two combination arms in first-line PDAC? I think you may have previously mentioned a number of 30 per cohort, but we were wondering if you were planning to expand the number before starting the pivotal study. And then we had a follow-up question if we could.
Hey, Jay. Great speaking with you, and thanks for the question. You're right.
So the targets for each of those combination arms are about 30 patients each. And so those are the targets that we're working with currently. And so we're really excited that we're already seeing a 43% ORR that's really dramatically higher than the benchmark that you would expect. The fact that the entire waterfall plot is pointing down is just really encouraging. It's highly consistent. The fact that across all three of the pancreatic cancer arms, we're seeing these clear activity, deep, profound regressions, and all that with just incredible tolerability. So we're excited with the data we have today.
Excellent. Super helpful. Thanks.
Any other follow-up questions? Yeah.
Yeah. Just as a follow-up, can you talk about your current thinking on the pivotal study, the timeline to starting the study? And are you planning to run the study independently?
Yeah. Great question, Jay.
The data we have here clearly supports the pivotal study and the planning that we're doing for that. Obviously, it's subject to regulatory authority feedback and the continuing data, but our goal is to start the study by the end of this year. That's the goal, or early next year. If things continue as they are, we think we can go very quickly towards the pivotal study. We're excited to do that, just given how differentiated these data are relative to the current options available for first-line pancreatic cancer patients. I mean, it's really a tough choice for them between the currently available options. For us to be able to come in with an option that has a much higher overall response rate, we're seeing a higher rate of complete response and target lesions, to have another 100% regression.
And then to do all that with such good tolerability, we believe it's kind of full speed ahead towards a pivotal trial.
Great. Super helpful. Congrats again on these really impressive results, and thanks so much for taking the questions.
Thank you, Jay.
Thank you. Our next question comes from the line of Allison Bratzel from Piper Sandler. Your line's open.
Hi. Good morning, team, and a big congrats on this data update. And thanks for taking my question. Maybe just one on potential dose response. Would you say you're seeing much in the way of a dose response for 104 on tolerability and efficacy between the 240 and the 320 MEK doses? I guess it's a little hard to see one just now, but obviously, it's limited data, and I'd be interested in your take.
And then on a related note, could you also talk to whether you're seeing a deepening of response over time? Just wondering if some of those patients with stable disease and only a couple scans might eventually get closer to response. Thanks.
Hey, Allison. Thanks. Great question. And you're absolutely right. I mean, if you look at the waterfall plot on slide seven, this is colored by dose, right? So you can see many of these patients are from the safety lead-in at 240, which makes the data, frankly, all the more exciting, right? To see such good responses at 240, and then have some initial patients at 320 is very encouraging as well. So we're exploring both doses, given just how profoundly strong the response is even at 240.
So in terms of activity, looking great at 240 and continuing to look great as we add in those 320 milligram patients. And as for the tolerability, there's not substantial differences. When we look at the monotherapy from phase I, there's maybe slight differences between the two, but it's not dramatic. And either way, it's just incredible tolerability. Whether it's 240 or 320, it's dramatically better tolerability than any MEK inhibitor any of us have seen before. So that combination is great, the combination of this just highly differentiated tolerability and then the strong response. In terms of the durability question, you're absolutely right. We've seen patients who have been 8% on a first scan, 10% reduction of lesions on a second scan, and then they drop down to 40% for a partial response.
So absolutely, I guess as another example of that, in the modified FOLFIRINOX arm, the patient with 100% regression, I believe that occurred on a second scan, right? And then was confirmed on a subsequent scan. But so that's another example where we absolutely do see deepening responses over time. And that's why we're so encouraged, really, across all three of these arms, that there are so many patients remaining on treatment and continuing. So really, we're excited to see how things progress for those patients as they continue on treatment. And they're able to continue on treatment because the tolerability is so good, and that's certainly a big part of it.
Excellent. Thanks so much.
Thank you, Allison.
Thank you. Our next question comes from the line of Graig Suvannavejh from Mizuho. The line's open. Great.
Thank you. Congrats, team, on the great data.
Really stellar, and thanks for taking my questions. I'm curious, given your plans to expand with three additional arms and also with your plans to start a pivotal, perhaps by year-end or early next year, could you just remind me your cash runway, I believe, on your third quarter update? You had a cash runway to second half of 2025. Could you just remind us kind of where you are and how you might think about funding on a go-forward basis? And then maybe a follow-up question, which is just on the data that you're seeing. I appreciate that you're moving forward. We're planning to move forward with the combination on one of the two first-line combinations that you're testing here.
Any thoughts in terms of the data that you showed us, if there were differences in the patients that were enrolled that might have led to different responses, or how do you envision the two combinations side by side if you do plan to move forward with 104 in a first-line setting? Thanks.
Hey, Greg. Thanks a lot for the question. And I actually really like the word you used, stellar, to describe the data. I think that's exactly right. These are stellar data. We're going to use that. Thank you. But in terms of funding, prior to today's announcement of the three new arms, we had guided to cash into the fourth quarter of 2025 based on our existing plans.
Given the stellar data in today's announcement, we believe we're going to have multiple options moving forward to fund all of these exciting new programs, either alone or in partnership with others. In terms of the data and the two different chemotherapy combinations, I think the data we have today from the 104 plus gemcitabine and nab-paclitaxel is so compelling, so profoundly different from what's currently available for first-line patients, right? To have a 43% ORR, to have a complete response, to have the whole waterfall plot going down, the left half of the waterfall plot missing, and to do all that with tolerability that we believe compares so favorably to historical benchmarks, it's just a very clear decision to move forward with the planning for that pivotal. I think with the other arms, we'll see, right?
The data is very encouraging with what we know to date, and as it continues to play out, I think we'll really make kind of independent decisions about each of the arms in terms of how we take them forward, but we're excited about all of them. I mean, if you look at the second-line monotherapy data, all those patients on the right half are continuing on treatment, right? So to Allison's earlier question about the durability and the fact that these responses sometimes develop after multiple scans and continue to deepen, we're really excited to see how that plays out, so continue to be very excited about each of these arms, and the data, we agree is stellar. Thank you, Graig. Next question.
Thank you. Our next question comes from Ami Fadia from Needham. The line's open.
Hi. Good morning.
Congrats from me as well on this very impressive dataset. I've got two questions. Firstly, just as we think about the data for the monotherapy in second line, can you give us some color on kind of the time you believe it takes for patients to respond? A lot of these patients are on stable disease. So I'm just curious if you anticipate some of these patients to convert into responding patients over time. If you could give us some color on sort of the average duration on treatment or the number of scans these patients received, that would be helpful. And then maybe a related question is, how are you thinking about the combination with sort of in other cancer types that you're looking to start cohorts for? Would you start with second line or third line?
Do you think ultimately IMM-1-104 would get developed as a combination in first-line treatment? Or so maybe just sort of how do you see that playing out? Thank you.
Ben, you might be on mute.
Thank you very much. Ami, thanks for the question. And absolutely, with regard to the time it takes for patients to respond in kind of the second-line monotherapy, absolutely, we're very optimistic about these patients who already have shrinking lesions. They're continuing on treatment. And as we mentioned earlier, we've seen multiple cases where the responses continue to deepen over time. And so we're optimistic to see how that plays out. I'd also point out that there's response, and then there's survival, right? And the patient we referenced earlier from the phase I, this is a really interesting case study that we're providing the update on today, right?
This is a patient with just a terribly large tumor. I mean, this is an 11 cm tumor in the third-line setting, patient who blew through FOLFIRINOX in the first line with progressive disease, blew through gemcitabine-containing regimen in the second line with progressive disease. And now on 104, for over 11 months, shrinking lesions down to 24% reduction in the target lesions. We're seeing reductions in the KRAS mutant ctDNA, a dramatic reduction from peak levels of CA19-9, that's the biomarker of tumor burden, as well as improved quality of life and weight gain. This is just, we think, a really profound example of the durability of 104, particularly if you think about what the PFS or survival expectations are in the third-line setting for pancreatic cancer.
So we believe even a patient who might technically be classified as stable disease like this one can really derive profound benefit that we believe will ultimately translate to a substantial survival benefit. So that's kind of how we think about response playing out over time. In terms of other combinations and the line of treatment, I think each of those situations is different. But look, first line is a great place to be, right? And I think we've set that precedent where we've taken 104 into first-line in pancreatic cancer in combination with the modified gemcitabine paclitaxel and the modified FOLFIRINOX. And this is really enabled by the tolerability profile, right? What lets us go to first line and combine with these chemos? It's the fact that 104 is so well tolerated. And it's great to see the 43% ORR, to see a complete response in this setting.
So we'll make each decision independently, but certainly in pancreatic cancer, the focus is on the first-line setting. And we're really excited about what these data show and kind of the profound difference over historical benchmarks. Thank you. Next question, please.
Thank you.
Thank you. Our next question comes from the line of Michael Yee from Jefferies. The line's open.
Hey, guys. This is Matt on for Mike. Congrats from us on these data, and thanks for taking our questions. Maybe just to expand a bit on the last question, I'm curious if you can speak to duration of response for those first two patients who responded and then just overall time on treatment for the patients overall, just thinking about overall durability.
I'm also curious if you can speak to what kind of improvement in PFS you would hope to see in a phase III study when you compare to standard of care chemo. Thanks so much.
Hey, Matt. Thanks for the question. Yeah, we're really encouraged by the durability. You can see it here in the number of scans and knowing that we do the scans approximately every six weeks, right? If you look at the median PFS just among the three patients that are already off treatment, right? Four of them are continuing on treatment. But just among the three that are off, you're looking at a seven-month median PFS, right, which is substantially higher than the five-and-a-half months from the chemo alone, the gemcitabine and paclitaxel alone. That's highly encouraging. We have another patient that was on for over eight months.
By the way, this patient only came off study due to an unrelated complication from a stent removal procedure, which unfortunately caused the patient to have to miss treatment for 43 days. It's unfortunate for that patient, but certainly, in a way, it's kind of validating the effect of the treatment that if you stop taking it for 43 days, it stops working. Overall, just really encouraging durability based on that. We're very excited for the potential for improving PFS and overall survival as the study matures. There's two parts to that. One is the activity, which we're clearly seeing, right? We're seeing this dramatically higher overall response rate than benchmark at 43%. It's also tolerability, right? The better tolerated therapy is the longer patients can stay on. We're really encouraged by that as well.
We're encouraged by, again, the durability of the patient from phase I who's been on for 11 months. So certainly, we're very optimistic about durability and survival and how that's going to play out over time.
Great. Super helpful. And congrats again.
Thank you. Next question.
Thank you. And our next question comes from the line of Jeff Hung from Morgan Stanley. The line's open.
Congratulations on the data, and thanks for taking my questions. You kind of touched upon this on the last question, but can you just talk a little bit more about why the 240 milligram CR and PR patients are no longer in treatments? And then I have a follow-up. Yeah.
Thanks, Jeff. So right, as I mentioned, the CR patient unfortunately had those complications from a stent removal unrelated to the treatment and had to stop taking the drug for 43 days.
So unfortunate for that patient, but again, kind of validates in a way the effect of the drug. The other PR patient who ultimately came off, but only after eight months on treatment, which again is well beyond the PFS expectation. That patient, basically, their target lesions, if the reduction so basically, if the lesions are 20% higher than the nadir, the lowest point, then they have to come off treatment per our protocol, so that patient ended treatment with a negative SLD. It went up enough from kind of the lowest point. But again, the fact that we saw such durability from those patients, seven months and eight months on treatment, with one of them coming off for reasons that were really unrelated to 104, we think bodes extremely well for the durability and the tolerability.
And then to see so many other patients continuing on treatment, not only in this arm, but in the FOLFIRINOX arm and in the monotherapy arm, and then to see 11-month durability so far for that patient in the phase I ongoing, we're just very encouraged by what we're seeing in terms of durability. And again, to have a 43% overall response rate, to have the entire waterfall going down, right, missing the left half of the waterfall, both in the Gemcitabine arm and the FOLFIRINOX arm, to have another 100% regression, right? Target lesions just don't go away on their own in pancreatic cancer. So to now see that twice, right? Lightning doesn't strike twice. To be able to see that twice, we find just really encouraging for the profound activity that we believe 104 can drive in pancreatic cancer, together with, again, unprecedented tolerability.
and the combination of the two, profound activity, unprecedented tolerability, we believe really just finally gives those first-line pancreatic cancer patients the potential for a better option where they don't have to choose whether they want to feel better or live longer. They can have a clear choice, a clear, obvious decision to live longer and feel better. That's what they deserve, and that's what we believe 104 can bring to them. Thank you, Jeff.
Great. Thanks. And then just a quick follow-up. For the pivotal trial, what is your current thinking on the dose of 104 you might pursue? Is there any reason to think that you might go higher than 320 milligrams in the pivotal? Thanks.
Yeah. I mean, look at the great results we're delivering even at 240, right, with a CR at 240.
Even if you look in the FOLFIRINOX arm, right, just advancing there, right, these are all at 240 as well. So the fact that we're seeing multiple patients with complete elimination of target lesions at 240, I think really it's encouraging. We're also looking at 320, but no, I wouldn't expect to go higher. I wouldn't think we would need to. I mean, we see really incredible activity and really encouraging tolerability. So no, we don't anticipate having to go higher than 320.
Great. Thanks, Ben.
Thank you, Jeff.
Thank you. Seeing as there are no more questions in the queue, that concludes our question-and-answer session. I will now turn the call back over to Mr. Ben Zeskind for closing remarks.
Great. I want to thank everyone for joining our call today, and we'd like to thank all the patients and investigators involved in our ongoing studies.
We look forward to updating you on our further progress in the coming year. Thank you, everyone.
Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.