Welcome to today's call. Lyell acquires exclusive global rights to a next-generation CAR T-cell product candidate in clinical development for metastatic colorectal cancer. For those of you who are joining us via Zoom, if you would like to ask a question, please raise your hand by clicking the raise hand at the bottom of your Zoom window. You can raise your hand at any point during the call to enter the queue, and you will be called upon during the Q&A session. Once called upon, please unmute your audio to ask your question. I will now pass the call over to your host, Ellen Rose, to begin today's presentation.
Thank you, Operator. Good morning, everyone, and welcome. Today, we are pleased to highlight our acquisition of exclusive global licensing rights for a novel next-generation CAR T-cell product candidate in phase I clinical development for metastatic colorectal cancer. Please review the press release in Form 8-K issued earlier today, along with the slides being presented on this call that can be found on the Investor pages of our website at lyell.com. Speakers on today's call include Dr. Lynn Seely, our President and Chief Executive Officer, Dr. David Shook, our Chief Medical Officer, and Dr. Gary Lee, our Chief Scientific Officer.
Before we begin, I would like to remind you that during today's presentation, we will be making forward-looking statements that are subject to certain risks, uncertainties, and other factors that could cause actual results to differ materially from those referred to in any forward-looking statements. For a discussion of the risks and uncertainties associated with our forward-looking statements, please see our press release issued today, as well as our most recent filings with the SEC. We disclaim any obligation to update our forward-looking statements. With that, I'd like to turn the call over to Lynn.
Thank you, Ellen, and welcome, everyone, to today's conference call. Since its founding, Lyell's purpose has been to give patients with cancer the gift of time by delivering on the promise of cell therapy. Lyell is focused on advancing next-generation autologous CAR T-cell therapies for patients with cancer, including both hematologic malignancies and solid tumors. We believe harnessing the patient's own immune system to deliver a one-time treatment with long-lasting benefit is the best way to bring patients with cancer what they are looking for: a return to their normal lives without ongoing treatment. Our vision is a world where more people with cancer can receive a one-time treatment with a cell therapy that delivers durable remissions and even cures. We continue to focus on hematologic malignancies with the aim of curing more patients and substantially improving outcomes.
In addition, we remain committed to aggressively pursuing the next wave of cell therapy innovation for solid tumors, which represent more than 90% of all cancers. Today, we are delighted to announce that Lyell has acquired exclusive global rights to a novel cell therapy in development for patients with colorectal cancer. We believe this candidate can transform the future of therapy for solid tumors. With this acquisition, we are well on our way to building an industry-leading pipeline of next-generation CAR T-cell therapies in oncology. Our strategy is to identify promising targets, those expressed at high levels in the majority of patients with a particular cancer type, to enhance benefit, and those that are expressed at low levels or are inaccessible in normal tissues to minimize side effects. We then arm our CAR T-cells with specific product enhancements designed to improve the T-cell's ability to fight cancer.
Specifically, our enhancements are designed to endow the cells with a greater ability to expand, maintain qualities of stemness, prevent exhaustion, and infiltrate tumors, all with the ultimate goal of increasing cancer cell killing. We are on a mission to develop one-time CAR T-cell therapies to deliver lasting remission or even cures for patients with cancer. Now, let's focus on our exciting new and very novel clinical stage CAR T-cell program in development for patients with metastatic colorectal cancer, LYL273. Colorectal cancer is the second leading cause of cancer death globally, and the incidence is rising in younger people. Better therapies are desperately needed as outcomes for these patients are very poor.
Data from a phase I clinical trial conducted in the United States at leading cell therapy centers evaluating our new product candidate, LYL273, showed a 67% overall response rate and an 83% disease control rate at the highest dose of LYL273 evaluated to date in patients with refractory metastatic colorectal cancer in the third or later line setting. Importantly, this clinical benefit was observed with a manageable safety profile. LYL273 is an autologous GCC-targeted CAR T-cell candidate enhanced with CD19 CAR expression and controlled cytokine release. Guanylyl cyclase, or GCC, is a target expressed on 95% of colorectal cancers and a majority of pancreatic cancers. The GCC CAR and the novel enhancements drive CAR T-cell expansion, immune cell infiltration, and cancer cell killing in the solid tumor microenvironment.
Under the terms of our exclusive license agreement, Innovative Cellular Therapeutics, or ICT, received at closing $40 million and 1.9 million shares of Lyell stock. ICT is eligible to receive additional cash and equity payments based on the achievement of certain clinical, regulatory, and commercial milestones, plus tiered royalties. We believe this is a tremendous opportunity to bring a potentially transformative therapy to patients with colorectal cancer and to further strengthen Lyell's pipeline with a clinical stage CAR T-cell therapy program for solid tumors with very promising U.S. clinical data. LYL273 is targeting a very large market. Not only is colorectal cancer the second leading cause of cancer deaths worldwide, it represents a large and growing $6 billion market that is projected to reach $12 billion in worldwide net sales by 2032.
There are more than 150,000 new cases and more than 50,000 deaths from colorectal cancer expected this year in the United States alone. Unfortunately, about 25% of colorectal cancer diagnoses occur late after the disease has already metastasized, and up to 60% of patients diagnosed with colorectal cancer will develop distant metastases at some point during their disease journey. The outcomes for patients with metastatic colorectal cancer are very poor. The median overall survival of patients in the third or later line setting is less than 12 months, and the overall response rates of approved therapies are less than 6%. This slide summarizes data from the pivotal trials of key standard-of-care therapies for patients with third or later line metastatic colorectal cancer. As you can see, patients need therapies with better efficacy. Partial and complete responses for these approved products are uncommon, achieved in only 6% or less of patients.
Median progression-free survival is six months or less, and the median overall survivals for these approved standard-of-care products are all less than 12 months. LYL273, formerly known as GCC19 CAR T, was first evaluated as single-agent therapy in China by ICT. Data establishing clinical proof of concept were published in JAMA Oncology in 2024. 15 patients with heavily pretreated refractory colorectal cancer were enrolled at a single center in China and received one of two dose levels following a single day of lymphodepletion. The overall response rate across both dose levels was 40%, with six patients achieving a partial response. The disease control rate was 73%, and at dose level two, the median overall survival was 25 months, and the median progression-free survival was six months. The safety profile was consistent with CAR T-cell therapy and included cytokine release syndrome, or CRS, immune effector cell-associated neurotoxicity, or ICANS, and leukopenia.
Grade 3 diarrhea was reported in more than 50% of patients. All events of diarrhea resolved. No deaths related to study drug were reported during the study treatment period. Before this single-center data, 20 patients were previously treated at multiple dose levels with earlier manufacturing processes at several different centers in China. During the study treatment period, five deaths were reported at these trial sites. The study was subsequently focused at one expert center with CAR T-cell therapy experience, and data from that center were published in JAMA Oncology. This case study describes one of the patients reported in that publication. The patient was a 48-year-old woman diagnosed with refractory metastatic colorectal cancer. She underwent surgical resection followed by four lines of chemotherapy and three courses of radiation to liver and lung metastases. She was eventually treated with two million CAR T-cells per kilogram.
Adverse events included grade 1 CRS, no ICANS, and grade 3 diarrhea, which resolved. You can see on the CT and PET scans on the right that the patient had a dramatic reduction in liver metastases with a partial response and 50% tumor reduction on CT scan, as well as a 96% reduction on PET scan. The duration of this partial response after the single-agent CAR T-cell therapy was eight months, and most importantly, this patient lived 46 months, almost four years following CAR T-cell therapy. Based on compelling cases such as these and an FDA-cleared IND, a clinical trial was undertaken in the United States. Now, let's turn to the impressive results seen thus far in the U.S. phase I dose- escalation dose- expansion trial in patients with metastatic colorectal cancer who received at least two prior lines of therapy before receiving single-agent LYL273.
A dose response with more and deeper responses following treatment at dose level two as compared with dose level one is evident. A 67% overall response rate has been observed in the first six patients treated at dose level two, with a 50% overall response rate across both dose groups. These high overall response rates, including one pathological complete response represented in green and one partial response with 100% target lesion tumor reduction, were achieved with a manageable safety profile. These data represent, to our knowledge, the best response rates observed to date in the third or later line setting in colorectal cancer. Before we dive more deeply into the clinical data, let's take a brief look at the mechanism of action that we believe gives LYL273 the potential to be a transformational cell therapy for patients with refractory colorectal cancer.
Cell therapy has seen lots of failures in solid tumors, most often for lack of efficacy. That lack of efficacy is generally associated with low CAR T-cell expansion, rapid cell exhaustion, and limited infiltration into the hostile tumor microenvironment. So, what is the breakthrough that is enabling the promising clinical data observed to date with LYL273? First, an excellent target has been identified. The target, guanylyl cyclase, or GCC, is highly expressed on more than 95% of colorectal cancers, including metastases. Its primary known role is to regulate intestinal fluid and electrolyte balance. A great target is necessary, but not sufficient for success. LYL273 GCC CAR T-cells are also armed with two enhancements, CD19 CARs and controlled cytokine release. The CD19 CAR expressing T-cells release cytokines after engaging B cells, resulting in expansion of CAR T-cells that express GCC CAR, CD19 CAR, or both.
When the GCC and cytokine-releasing CD19 CAR T-cells expand, they can infiltrate into tumors and kill cancer cells. It is this partnering of GCC CARs with CD19 CARs, plus the controlled cytokine release, that are central to the scientific breakthrough of this novel CAR T-cell product candidate. Now, let's dive into the clinical data and mechanism of action in more detail so you get a very clear understanding of why we are so enthusiastic about this next-generation solid tumor program. Dr. David Shook, Lyell's Chief Medical Officer, will now tell you in more detail about the clinical data from the ongoing phase I trial of LYL273. Dave?
Thank you, Lynn. I'm excited to have the opportunity to discuss the U.S. phase I clinical trial for LYL273. As you have heard, this trial was initiated following proof of concept data from a single center in China. A U.S. IND was then filed, and a dose- escalation dose- expansion trial was initiated at four expert cell therapy centers: Dana-Farber, UCSF, University of Colorado, and City of Hope. Today, I will review data from 12 patients, including six patients treated at dose level one, one million CAR T-cells per kilogram, and six patients at dose level two, two million CAR T-cells per kilogram, as of the data cutoff of October 28, 2025. The key inclusion criteria required patients to have metastatic colorectal cancer that had progressed following at least two prior lines of therapy.
All patients had at least one measurable lesion by RECIST 1.1. Patients with liver metastases were allowed but were limited to no more than seven lesions, with the largest less than three centimeters. Enrolled patients had no curative surgical options. The treated patients were relatively young, with a median overall age of 49 years. They had received between two and six prior lines of therapy, with a median of two prior lines. The median number of involved disease sites, such as lung or liver, was two, with a maximum of three. All patients had microsatellite stable disease, and one-third were RAS-mutated. The study population represents patients who have a poor prognosis. The median age reflects both the rising incidence of colorectal cancer in younger patients and the desire of investigators to include generally fit patients in this phase I clinical trial. Moving to safety, let's review the adverse events of interest and other common events. The grade 1 and grade 2 CRS events were short and resolved with standard therapy. As you can see, no cases of grade 3 or higher CRS were reported.
There were two cases of ICANS at dose level two, one grade 2 event, and one grade 3 event that resolved in three days. Diarrhea was the most common event, with a median duration of 11 days. Grade 1 or 2 diarrhea occurred in 58% of patients. One patient treated at dose level two experienced a dose-limiting toxicity of grade 3 diarrhea that evolved to include an event of grade 4 colitis requiring treatment with aggressive immunosuppression. Unfortunately, the patient died of fungal sepsis 48 days after the infusion. The management of diarrhea was then optimized, including protocol-directed medical prophylaxis, resulting in markedly improved symptom control such that the last three patients treated did not experience grade 3 or higher diarrhea. Other common adverse events included grade 1 or 2 fatigue and nausea. Overall, the emerging safety profile of LYL273 is manageable.
Now, let's take a detailed look at the clinical outcomes of the treated patients. This table shows the dose-dependent best overall response rates, with a 67% overall response rate at dose level two, the highest CAR T-cell dose evaluated to date. Three patients achieved confirmed partial responses. One patient who had over 600 pulmonary lesions at baseline had a partial response at day 28, followed by a pathological complete response with no evidence of cancer at autopsy. An 83% disease control rate was observed. This included patients with complete and partial responses as well as stable disease as their best overall response. The median progression-free survival at dose level two was 7.8 months. The median overall survival was 17 months at dose level one and was not reached at dose level two.
As a reminder, these patients had already progressed despite multiple prior lines of approved therapy, so these response rates are quite remarkable. Lynn has already reviewed the impressive waterfall plots with you, showing each patient's best overall response with deepening in response in dose level two as compared to dose level one. Here you can see at dose level two the pathological complete response in patient 12 in green, as well as the three partial responses in patients nine, 10, and 11 reflected in blue, including patient 11 with complete resolution of all target lesions. Each lane in the swimmer plot on the right-hand side of the slide represents a patient, and the patient numbers on the waterfall plot represent the same patients on the swimmer plot. As in the waterfall plot, dark blue represents partial response, and light blue represents stable disease.
The dotted swim lanes indicate survival following progression or censoring. For example, patient 10, who had a partial response until month eight, survives beyond 18 months, and patient 11 remains in partial response through month 15. Overall, these response rates and early survival data are very promising in a high-risk population with traditionally dismal outcomes. Here, we outline a case study of patient 11, a 54-year-old woman treated with LYL273 in the U.S. clinical trial. She was diagnosed with stage 4B colorectal cancer and developed liver and lung metastases less than six months after her initial cancer resection. Her disease progressed despite three lines of intensive approved therapy. She was then treated with LYL273 at dose level two following a single day of protocol-directed lymphodepletion.
She had grade 1 CRS, no evidence of ICANS, grade 1 diarrhea for three days starting on day 12, and she was discharged from the hospital on day 15 with no serious adverse events. Despite having cancer that had progressed through three prior lines of therapy, she achieved a partial response at her month one visit, and that response continued to deepen over time following a single infusion of LYL273. The CT images on the right side of the slide highlight the improvement of one of the target lesions in the right lung. All target lesions were resolved by month 10, and she continues to do well as of her last study visit at month 15.
Of note, this patient does not meet RECIST criteria for a complete response because she had resection of an irradiated non-target lesion at month seven that was found to have a microscopic focus of adenocarcinoma on histology. She has received no further systemic therapy. In summary, I hope that I have demonstrated why we are so enthusiastic about LYL273's significant and durable antitumor activity in patients with refractory colorectal cancer. The safety profile is manageable and consistent with the GCC-targeted mechanism of action and CAR T-cell therapy. Enrollment is continuing in the phase I trial, and the next data update for this program is expected in the first half of 2026. Now, I'd like to turn the call over to Dr. Gary Lee, Lyell's Chief Scientific Officer, who will highlight the construct and mechanism of action of LYL273. Gary.
Thank you, Dave. To deliver meaningful clinical benefit to patients with solid tumors, CAR T-cell therapies need to address multiple challenges. First, the right target antigen to mediate tumor-specific killing must be identified. For metastatic colorectal cancer, we believe we found that in guanylyl cyclase C. GCC is highly and specifically expressed in colorectal epithelial cells, with limited to no expression outside of the gastrointestinal tract. In addition, in healthy colorectal epithelial cells, GCC expression is limited to the apical surface of the side facing into the colon, making it significantly less accessible to immune cells or CAR T-cells coming from the bloodstream. This means the risk of on-target, off-tumor CAR T-cell activity in healthy tissues is manageable. This property is critical to enable a therapeutic window for CAR T-cells to target tumor cells.
In colorectal cancers, this polarity in GCC expression becomes disrupted, exposing the GCC antigen to CAR T-cells to target and kill while sparing the adjacent healthy GI tissue. However, in solid tumors, a great target antigen is not enough. LYL273 is designed to overcome two critical barriers. The first is insufficient in vivo expansion or engraftment post-infusion due to the lack of readily available CAR antigens. The second is the dense hostile or immunologically cold tumor microenvironment that employs multiple mechanisms to suppress T-cell infiltration, activation, and tumor killing. In LYL273, we've incorporated a GCC CAR, which directs the CAR T-cells specifically to colorectal cancer. We have further armed LYL273 with multiple enhancements designed to facilitate in vivo expansion, which in turn leads to infiltration and antitumor activity.
We've added a CD19 CAR to jump-start CAR T-cell expansion upon infusion by engaging B cells, removing the requirement that CAR T-cells must first encounter the cancer before getting the critical expansion signals. LYL273 is engineered to release three different cytokines upon T-cell activation. These cytokines are designed to further improve cell expansion, create tumor inflammation, and enhance immune cell infiltration and the killing of cancer cells. The level of cytokine release is regulated by specific vector design and usage during manufacturing. LYL273 is a single-infusion product that consists of three key CAR T-cell types. We are able to package all of the enhancements into a single product candidate by simultaneous transduction with multiple vectors at a defined ratio. A robust seven-day manufacturing process produces consistent CAR product lots with three key CAR cell types: GCC CAR T-cells, CD19 CAR T-cells, and GCC CD19 doublet CAR T-cells.
We believe each of the three CAR cell types plays an important role in mediating the clinical responses Dave described earlier, but perhaps the most interesting and unique cell type is the CAR T-cell that expresses both the GCC and CD19 CARs, which we refer to as GCC CD19 doublet CAR T-cells. The GCC CAR component directs cancer-specific killing activity. The CD19 CAR T-cells utilize normal B cells to jump-start in vivo T-cell expansion and cytokine release, providing the necessary signals to sustain the CAR T-cells to infiltrate the cancer. Critically, this process results in preferential expansion of the doublet CAR T-cell component of LYL273, also expanding and releasing cytokines upon engagement of B cells, and effectively increasing the frequency of total GCC CAR-expressing T-cells in circulation. Finally, LYL273 is engineered to release three cytokines: interleukin-12, interferon gamma, and interleukin-6 in a controlled and proportional manner.
The purpose of the cytokines is to prime the tumor microenvironment and the CAR T-cells themselves for improved infiltration and tumor killing. And how do these populations work together to achieve the remarkable responses observed in patients with colorectal cancer? As shown in panel one, the first unique feature of LYL273 is the CD19 CAR that drives initial expansion upon binding B cells and releasing cytokines that feed back and aid all of the CAR T-cells. As a result, the GCC CD19 doublet CAR T-cells start to multiply. These cells become available to attack the cancer cells, but importantly, avoid attacking healthy cells in the polarized gut epithelium, sequestering the GCC antigen from circulation. In panel two, we depict the finely tuned cytokines making it into the tumor, creating antitumor inflammation, and beginning to warm up the cold immunosuppressive microenvironment.
Leveraging the cytokine support from the CD19 CAR B cell interaction, the invigorated GCC CAR-expressing T-cells are primed for tumor infiltration and killing. In panel three, in this more permissive remodeled immune environment, the GCC CAR-expressing T-cells are less hindered and can mediate the killing of the cancer cells. Our translational data indeed supports this proposed mechanism of action. Here, we're showing the measured level of the three key CAR T-cell types in a patient with a durable partial response. As you can see, the GCC CD19 doublet CAR T-cell type, shown in blue, was a minor proportion initially but rapidly expanded after LYL273 treatment during the critical window of approximately 7-14 days post-infusion.
In fact, at peak expansion, the GCC CD19 doublet CAR T-cells represent more than 80% of all GCC CAR-expressing T-cells, a remarkable observation and clear demonstration of the impact made by the CD19 CAR enhancement. It is noteworthy, however, that the single positive GCC CAR T-cells, shown in orange, were initially expanded at a less rapid pace, but at later time points, this population once again became the dominant CAR T-cell type to continue cancer cell killing and surveillance. We have built a sophisticated translational study plan to further interrogate and better understand this unique and fascinating mechanism that underlies the clinical activity reported. We look forward to sharing more data in the future. Lastly, I would like to emphasize that while the GCC CAR and enhancement components are unique, the manufacturing of LYL273 is very similar to other autologous CAR T-cell products.
Our current process utilizes the Miltenyi CliniMACS Prodigy instrument, which is designed to be a closed automated system. The current process is seven days and is transferable and scalable, and we anticipate the automated manufacturing process will fit seamlessly into our wholly owned Lyell manufacturing facility footprint. Now, I would like to turn the call back to Lynn for highlights of the transaction and closing remarks. Lynn.
Thank you, Gary. I'm pleased to share the terms and strategic rationale for our licensing agreement. The addition of LYL273 to our pipeline is strongly aligned with our mission of developing next-generation CAR T-cell therapies that give patients with cancer the gift of time. The transaction augments our product pipeline with a solid tumor program that leverages our clinical, scientific, and manufacturing expertise. LYL273 has very compelling initial clinical data in an area of high unmet need.
The metastatic colorectal cancer market is large and growing, and LYL273 offers the potential for substantial improvement over the current standard of care in late-line colorectal cancer and the potential to expand into other GCC-expressing tumor types, such as pancreatic cancer. Under the terms of the definitive agreement, Lyell receives exclusive global rights outside of mainland China, Hong Kong, Macau, and Taiwan to develop, manufacture, and commercialize LYL273. ICT received an upfront payment of $40 million and 1.9 million shares of Lyell's stock. ICT is also eligible to receive additional cash and equity payments based on the achievement of certain clinical, regulatory, and commercial milestones, including up to $30 million in clinical milestones, with the remainder of the cash payments at late-stage regulatory or commercial milestones. There is also additional equity consideration for specific clinical and regulatory milestones, along with tiered royalties on annual net sales.
With the close of this transaction, we are now well on our way to developing a robust pipeline of next-generation CAR T-cell programs. As announced last week, we are presenting new clinical and translational data from our phase I clinical trial of RhondaCell, an autologous dual-targeting CD19, CD20 CAR T-cell product candidate in patients with aggressive large B-cell lymphoma at the American Society of Hematology Conference in December. We are also focused on rapidly advancing the pivotal development of RhondaCell through our two registration clinical trials. Pinnacle, our single-arm pivotal trial, is enrolling patients with relapsed and/or refractory large B-cell lymphoma in the third or later line. This trial is expected to form the basis of a BLA submission in 2027.
And our second pivotal trial, a phase III head-to-head CAR T-cell therapy randomized control trial of RhondaCell for large B-cell lymphoma in the second line, is expected to begin enrolling patients by early 2026. The phase I trial of LYL273 continues to enroll patients, and we expect to share updated clinical data in the first half of 2026. And finally, we're progressing a fully armed CAR T-cell candidate with an undisclosed target and expect to file an IND in 2026. Before we conclude, I want to highlight two important updates on RhondaCell. I am pleased to announce that we have been granted Regenerative Medicine Advanced Therapy, or RMAT, designation for RhondaCell for patients with relapsed or refractory large B-cell lymphoma receiving treatment in the second-line setting. This FDA designation complements the RMAT designation in the third or later line setting received in April this year.
RMAT designation recognizes the potential of RhondaCell to address significant unmet needs of patients with large B-cell lymphoma and enables an increased frequency of communications with FDA on the development of RhondaCell. And here you can see the titles of our two oral presentations at ASH. Before we open the call for Q&A, I want to summarize why we are so optimistic about our ability to deliver value over the coming months. Our lead program, RhondaCell, has the potential to be a new standard of care for aggressive large B-cell lymphoma. The phase I trial has demonstrated high response rates in high-risk patients with a safety profile appropriate for outpatient administration. The newest addition to our pipeline, LYL273, has very promising initial clinical data in a phase I trial with high response rates in refractory patients with metastatic colorectal cancer and a manageable safety profile.
The U.S. phase I trial is continuing to enroll patients, and we look forward to sharing more about this program as we take over responsibility for its execution. Importantly, we own and operate our Lyell manufacturing facility in Bothell, Washington, where we can produce more than 1,200 doses per year at full capacity. This facility is capable of supplying the clinical needs for each program, as well as supporting early commercial launch. Finally, we have a strong balance sheet with $347 million of cash as of the end of the second quarter, which we expect, inclusive of this transaction, to provide cash runway into 2027 through multiple clinical milestones for RhondaCell and LYL273. We look forward to continued execution on our pipeline, taking full advantage of our expertise in CAR T-cell clinical development and our wholly owned manufacturing facility. Now, I'd like to open the call for questions. Operator.
We will now move into our Q&A session. For those of you who are joining us via Zoom, if you would like to ask a question at this time, please raise your hand by clicking the raise hand at the bottom of your Zoom window. Once called upon, please unmute your audio and ask your question. Our first question will come from Mitchell Kapoor with H.C. Wainwright.
Good morning. Thank you. This is a lovely talk. Could you expand a little bit more on your results from the prophylactic treatment for diarrhea? The population that we're looking at seems kind of small still, so I was wondering if you could provide some more color on your confidence on how this will apply across a broader population, and then maybe touch on what we might look for in future data releases to confirm that everything's going according to plan.
Sure. Thanks for the question. Dave, why don't you start by speaking to the diarrhea treatment protocol?
Sure. Thanks for the question. Yeah, we're confident in the management going forward of the diarrhea. As we mentioned, there was some heterogeneity across the protocol, and then there's standardization of both prophylaxis and management after. And while there were only three patients, none of those patients developed diarrhea greater than grade two, and it was a very short duration. And so we are confident moving forward with that.
Yeah. So as you might imagine, with cancer therapy, it's always a strategy to maximize the benefit while mitigating the risk. And much the way in CAR T-cell therapy, where initially we learned how to manage CRS and ICANS, I think this is a situation where diarrhea is an adverse event we have to be aware of. But I think the investigators have done an excellent job of coming up with this proactive treatment management protocol, which appears really to be working well. So more to come on that, but we are obviously confident otherwise we've been doing the sale. And in terms of future data release, the phase I trial is continuing to enroll, and we'll be providing additional data on more patients in the first half.
Great. Thank you guys so much.
Your next question will come from Shunatra Mishra with Goldman Sachs.
Hi, this is Shunatra from Goldman Sachs. Thank you for taking our question. So a couple of quick ones from me. So will you be at some point exploring the potential of this asset in earlier lines, solid tumors, and also regarding the one death due to grade colitis? Anything to call out on baseline characteristics which could possibly explain this outcome, or do you think it was just related to the heterogeneity that you referred to a while ago?
Yeah. So why don't I start, and then Dave can speak more to the patient that died. So this program has broad potential, as you might imagine. We are focused right now on late-stage metastatic colorectal cancer. It is certainly possible that there may be opportunity down the road to explore earlier lines. It's also very interesting that GCC is expressed on other cancers, and in fact, it appears to be expressed on the majority of pancreatic cancers. So this is a tremendous opportunity, but obviously, for right now, we'll be focused on the third- or later-line metastatic colorectal cancer. And then, Dave, maybe you want to speak to the other question?
Sure. Yeah. The patient that you mentioned, he was a 49-year-old with really refractory disease, had seen surgery, radiation, and multiple lines of aggressive chemotherapy before coming on to LYL273, received therapy relatively uneventfully, and then throughout the course developed diarrhea that initially severity wasn't fully appreciated because of had less frequent but really large volume diarrhea, and we believe just sort of wasn't fully appreciated or addressed. And then later, as diarrhea evolved, that patient received immunosuppression, aggressive immunosuppression that we felt was, in retrospect, kind of catching up for what now the prophylaxis addresses.
And you mentioned burden of disease or other disease factors. It's a single case, so it's hard to pull out any specifics that might do that. A patient had over 600 pulmonary lesions at baseline and then had partial response at month one. So really impressive clinical results. Then afterwards, the diarrhea, I think, required immunosuppression and the subsequent infection from that. So moving forward, I think really the prophylaxis is going to be helpful in managing this kind of patient really before it gets to that point. Obviously, it was a lot, but we're encouraged moving forward by both the response and the management plan.
Just to underscore, I think there's a lot of learning going on here, and I think that now the investigators feel much more confident about the management of these cases and are treating very early with prophylaxis and aggressively.
Understood. Thank you so much.
Y our next question will come from Jason Zemansky with Bo f A.
Hi. Good morning. This is Jackie on for Jason. Thanks for taking your call. Sorry. Yeah. Thanks for taking your question and congrats on the progress. So yeah, just a few quick questions. So what does this mean for your current solid tumor platform? How are you prioritizing this newly acquired asset with your own pipeline? And finally, what lessons have you learned from your ROR1 targeting CAR T-cells that can be applied here? Thanks.
Thanks, Jackie. I appreciate the question. So obviously, we are extremely excited about this opportunity in front of us. When you have a treatment for colorectal cancer that has a 67% overall response rate, that is a really exciting opportunity. So clearly, we're going to continue to move this forward as quickly as possible. That being said, we also are extremely enthusiastic about our RhondaCell program, which is in pivotal trials, as you just heard, and just received RMAT designation in the second line from the FDA. So that's full steam ahead.
And then we do have a very active and very promising research program with our own solid tumor program. So we are in an amazing situation to have this nicely diversified portfolio with a late-stage hematologic CAR T-cell program, now moving forward, colorectal CAR T-cell program, and then an undisclosed program coming up in our research team. So we're really pleased with the way our portfolio is evolving. And I think we've developed across time a lot of expertise in cell therapy, both translational science, clinical development, and manufacturing. And we are up for this challenge and believe that this is just a tremendous opportunity. We're thrilled that we were able to bring it into the company and look forward to moving it ahead.
Great. Thank you so much.
Our last question will come from Christopher Liu with Lucid.
Hey, guys. Thanks for the question. Congrats on the acquisition of the asset. For the first question, just wondering what your thoughts are on the clinically meaningful amount of responses and durability you might need to see in colorectal cancer. For the second question, where do you see this asset positioned with some competition in the colorectal cancer pipeline with, for example, RAS- targeted agents as well as CTLA-4 agents?
Sure. I think we showed the data from the products which are currently used in our standard of care in the third or later line setting. You saw that the response rates are 6% or less. You saw that the median progression-free survival is less than six months, and the median overall survival is less than 12 months. That's the bar.
The fact that we are seeing 67% overall response rates means that we've got a lot of room to show meaningful results here. In colorectal cancer, overall response rates, I mean, many, many of these patients have median progression-free survival or median progression at the two-month visit. I think we're in great position to show benefit and to be very strongly competitive in the third or later line.
There are other products coming, of course, but this mechanism is completely novel. There are no other GCC targeted programs in development at this point. We believe that this is a disease with a very dismal prognosis, and we need lots of new therapies coming. I think that's great for the KRAS targeted products and for others, but this is a unique mechanism, and we think it's going to have a significant role in the treatment of these patients, particularly in later line setting.
One more, if I may. Is there a pathway you think towards earlier line? And I'm sorry if I missed this, but do you think there's a pathway towards earlier lines, potentially something like front line in the future?
It's early days, and I wouldn't go so far as to say we'll be jumping immediately to front line. Our goal is going to be to get this approved as quickly as possible in the later line setting. But that being said, yes, I do think there is room to take this product into earlier line, particularly as we get better and better at managing the safety profile. So more to come on that, but I think right now we will focus in the later line and see how the data mature.
Thank you very much.
There are no further questions. I will now hand the call back to Lynn Seely for closing remarks.
Well, thank you all for joining us this morning. We look forward to continuing to execute for patients, and we'll continue to update you on our progress. Thank you very much.