All right. Good morning, everyone. Thank you for joining us today. My name is Chris Holt, and I have the pleasure of introducing our speaker today. Before I hand things over, though, I just wanna call your attention to the blue button on your screen, which is where you can ask questions for the Q&A session later in this session that we have together. Without further ado, I'd just like to hand things over to Steven Nichtberger with Cabaletta Bio. Steven, the floor is yours. Thank you.
Thanks. Thanks, Chris, and thanks to our friends at J.P. Morgan for the opportunity to provide this update this morning. Starting off with slide three, Cabaletta was formed in order to develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases. On slide four, you can see that we're doing this by developing highly specific CAR T products to treat B-cell mediated autoimmune diseases. We're going after targets where there's a biologic opportunity for a deep and a durable response, perhaps even a cure. We're leveraging a clinically validated CAR T product design and manufacturing process through our partnership with the University of Pennsylvania. Our DesCAARTes trial in patients with mucosal pemphigus vulgaris is ongoing.
To date, we've reported no dose-limiting toxicities, nor any clinically relevant adverse events in any patient in the first three dosing cohorts, which are the 20, 100, and 500 million cell dose cohorts. These patients have not received lymphodepletion, and they also do have circulating soluble antibodies. There was no clear evidence of biologic activity observed in the first two low-dose cohorts, the 20 and the 100 million cell dose cohorts as of December. These two cohorts use doses that are less than 2% of the currently planned maximum dose we will evaluate in this trial. Our dose escalation plan includes the potential for up to a 375-fold increase in dose from 20 million up to 7.5 billion cells across five cohorts.
Importantly, we did see a dose-dependent increase in DSG3-CAART persistence in the third cohort relative to the first two cohorts during the first 28 days. Our cell therapy pipeline addresses about 80,000 patients in the U.S. Our lead preclinical program is for patients with myasthenia gravis, and an IND was submitted in the fourth quarter on that program. We plan to initiate the clinical study for myasthenia gravis in 2022, pending FDA clearance of that IND. Behind that, we have a program for patients with PLA2R-associated membranous nephropathy. A pre-IND interaction with FDA was completed in the fourth quarter. Our cash runway guidance is through the first quarter of 2023 at least.
We have about $120 million in the bank at the end of the third quarter, and historically, for reference, we've spent about $10 million per quarter in the past. We have a lot of flexibility. Turning to slide five, our scientific platform leverages a clinically validated CAR T technology, which has been approved for the treatment of hematologic malignancies. In contrast to CAR 19 products that are designed to kill all B-cells, our products are designed to destroy only the 1% or less of the B-cell population that is causing a specific autoimmune disease. When you make a typical CAR T product, you start with the patient's own T-cell. You genetically modify it by adding a signaling domain and a costimulatory domain, as well as targeting domain, which is an antibody fragment directed to the CD19 antigen found on all B-cells.
Successful therapy will result in the elimination of all B cells, both normal and cancerous, leaving the patient with no humoral immunity. To make a highly targeted CAR T cell, we change only the targeting domain. Excuse me. Instead of using an antibody fragment as the targeting domain, we use the antigen that is the subject of attack in an autoimmune disease. That antigen will be recognized by the B cell receptor that is only found on pathogenic autoreactive B cells. When the two cells meet, the T cell will destroy the B cell. Normal B cells will not recognize the CAR T cell that we develop, so the patient will be left, after successful therapy, with a normal immune system.
Turning to slide six. As shown on this chart, cell therapy has been thoroughly explored in cancer. We believe there's a great adjacent opportunity in the autoimmune field, which is increasingly being recognized. Our CAR platform has the potential to treat and perhaps cure many B-cell-mediated autoimmune disease patients using the basis of a CAR 19 technology that sparked the cell therapy revolution. Our current platform offers the opportunity for specific treatment of up to 80,000 patients in the U.S. alone.
Turning to slide seven. Our platform is highly modular. We use the identical killing mechanism and change only the targeting domain to develop a new product. Excuse me. The platform allows us to be highly capital efficient while pursuing a broad range of programs, from pemphigus vulgaris to myasthenia gravis to membranous nephropathy. On slide eight, you see a summary of our current pipeline, where I would highlight the mucosal pemphigus vulgaris program in the clinic, the MuSK program with an IND recently filed, and the PLA2R program, where we recently completed a routine pre-IND interaction with FDA.
Now I'd like to focus our attention on our lead clinical program for mucosal pemphigus vulgaris. On slide 10, you see that pemphigus vulgaris is a painful blistering skin disease, which is currently treated with broad immunosuppression. Most patients have exacerbations and remissions throughout their lives despite optimal therapy. Rituximab is among the leading therapies for pemphigus vulgaris. Data on rituximab are summarized on this slide, along with many references. While it seems to be effective when administered along with 3,500 milligrams of steroids per year, providing a 40% chance of a four-month hiatus from the disease and from medicines, it's expected that most of these patients will relapse despite repeated therapy, and many others will never respond. In addition, there's a 22% annual serious adverse event rate associated with rituximab in pemphigus vulgaris. We believe that patients need more effective and safer treatment options.
Turning to slide 11. This slide is designed to be generalized for you to understand how we develop products for a new target. In mucosal pemphigus vulgaris, we know that the DSG3 antibody is necessary and sufficient to cause disease. Thus, elimination of the B cells that make the antibodies should result in a clinical response, perhaps even a cure. To design the CAR, we start with the DSG3 antigen shown at the top left box. It has five extracellular domains. 91% of the patients have antibodies against the first extracellular domain, EC1, 71% against EC2, and so on. The polyclonal nature of the disease requires that we design a product to address all potential clones. To do this, we incorporated all of the DSG3 extracellular domains in the targeting domain of our product, except for EC5, which is known to not cause disease in humans.
Shown on the right panel is our product for PV, along with antibodies that should be attracted to our targeting domain. Below each antibody name are the epitopes that would be specifically recognized by the antibody. Together, these represent all known epitopes that trigger pemphigus vulgaris disease. Thus, one product is designed to treat and perhaps cure all patients with mucosal pemphigus vulgaris. On slide 12, you see the DesCAARTes trial summarized. It's a Phase I trial of the DSG3-CAART product designed to evaluate a 375-fold dose range from 20 million up to 7.5 billion cells. Enrollment criteria include the vast majority of all diagnosed patients with an exacerbation, any patient with DSG3 antibodies, and a clinical disease who has failed at least one therapy. We're currently dosing the 2.5 billion cell dose cohort.
While we've used four dosing fractions for each of the doses previously administered, based on our safety data to date as discussed with FDA, we are starting the fifth cohort with only two fractions. We plan to consolidate the therapy going forward in all future cohorts. On slide 13, you see clinical assessments and timelines. We believe that acute safety within the first 28 days is the most relevant measure of safety because CRS and neurotoxicity are known to be the most significant adverse events, and they occur within this window. On the efficacy side, because our product is designed to kill the B cells that are responsible for antibodies that cause the disease, we would expect to detect early signs of biologic activity about three to six months after treatment.
On slide 14, you know, the slide reflects progress that we've reported to date with the trial. To date, we've reported on the first three cohorts, up to 500 million cells, and there have been no dose-limiting toxicities, nor any related clinical adverse events of any consequence in any patient. Because we target fewer than 1% of the B-cell population and because CRS and neurotoxicity are associated with the total burden of B cells destroyed, we believe that the risk of acute side effects in this trial are substantially reduced versus CART19 therapy. As a result, our investigators, advisors, and FDA have agreed that patients can be treated on an outpatient basis in the trial. Recently, we also reported that we did not see clear evidence of biologic activity in the first two dose cohorts.
These two cohorts include doses that represent less than 2% of the maximum dose that we plan to evaluate in the trial. Turning to slide 15. This is probably the most important slide in this presentation. Based on our early safety data, we can advance our plans to maximize drug exposure in order to find and kill the 1% or less of targeted B cells in order to maximize the probability of biologic activity and clinical efficacy. There are many opportunities to realize the full potential of this biology. First, we can increase the dose, perhaps up to 10 or 12 billion cells. This range of doses has been used with long-term engraftment seen in a non-cancer population. Second, we can evaluate, if needed, repeat dosing over the course of a month or two to ensure prolonged drug exposure if warranted.
Third, in the trial, patients can be retreated if they were previously safely treated with an insufficient clinical effect. Fourth, we can increase the number of central memory cells in our product, which we know are already present, and these cells will track to the secondary lymphoid tissues where the target B cells reside, increasing the potency of our product by enhancing our manufacturing process with routine advances that can now be incorporated into our process given the exceptional early safety data. Fifth, we continue to consider various preconditioning strategies if warranted, including the potential to use IVIG as a preconditioning regimen because its treatment effect lasts only for a period of weeks. This would reduce the soluble circulating antibody, if warranted, and allow us to have the ability to read out the effect of our product.
In addition, we continue to consider the possibility of using more classic forms of preconditioning. Finally, there are additional approaches that the company is actively evaluating to enhance CAR T expansion post-infusion. With $120 million in cash at the end of 3Q 2021, we're comfortable that we have the resources necessary to pursue these opportunities. Let's turn our attention now to the MuSK myasthenia gravis program. On slide 17, you know, myasthenia gravis is a particularly attractive opportunity for the company and for our platform because it shares many of the same biology characteristics as pemphigus vulgaris, and this is shown on the left panel. Similar to DSG3 CAR T, our MuSK contains all known epitopes. The unmet need is substantial, with limited treatment options and a clinical profile that's typically more severe than other forms of the disease.
On slide 18, you see peer-reviewed data that's previously been presented, and it demonstrates that the MuSK CAR specifically eliminates anti-MuSK target cells in an animal model where CART19 cells were a positive control and DSG3 CAR cells were a negative control. The IND for the MuSK CAR, which has been substantially informed by our experience with DSG3 CAR, has recently been submitted to FDA. Turning now to membranous nephropathy and the PLA2R CAR. On slide 20, this is another target which has compelling biologic rationale. PLA2R antibodies are increasingly being accepted as the primary cause of membranous nephropathy in many patients with primary membranous nephropathy. This disease can lead to dialysis or kidney transplantation in about a third of patients who don't experience remission within the first six months. The PLA2R antigen is very well described and the epitopes are well defined.
Patients are also easily identified. A pre-IND interaction was recently completed with FDA. On slide 21, you see peer-reviewed data that were presented at ASN Kidney Week in 2021, which demonstrated in vitro antigen-specific killing in the presence of anti-PLA2R antibodies. Similar to DSG3 CAR T, a membrane protein array demonstrated no off-target binding interactions. We're excited about our overall portfolio, most of all our lead program, and all of it depends on successful manufacturing. Let's turn our attention to slide 23. Our manufacturing strategy is highly capital efficient and has delivered high-quality product safely and on time over the past couple of years. Stage one of our strategy included a partnership with the University of Pennsylvania and the Children's Hospital of Philadelphia to support the DesCAARTes trial.
Stage two of our strategy includes now established partnerships with WuXi and Oxford Biomedica recently announced to support the MuSK-CAART clinical program. Our stage three strategy will include a Cabaletta-owned GMP facility, which will be secured based on a data-gated strategy. When we see sufficient data, we will invest in our own facility. Turning to a brief overview of Cabaletta Bio leadership. The leadership team at Cabaletta has very deep and highly relevant experience innovating within the cell therapy industry. The team is unified in our vision and our belief that the elegant biology platform that we are pursuing has the potential to offer a leap forward, perhaps even a cure, for many patients with B-cell-mediated autoimmune diseases. We're pleased also to welcome the newest member of our scientific advisory board, Dr. Drew Weissman.
Drew Weissman is an inventor of the mRNA technology found within the COVID vaccines, and he's an immunologist by training who brings expertise not only in immunology, but the targeted application of mRNA technologies. On slide 26, in closing, we enter 2022 on a strong foundation of timely execution and promising safety data with the opportunity to fully explore higher doses and other strategies to increase drug exposure of our product in partnership with an expanding network of academic and industry partners. We expect to present the 28-day data, safety data on the 2.5 billion cell dose cohort in the first quarter of 2022, despite some recent scheduling challenges related to the holidays and the recent COVID surge. We expect to present future clinical data at scientific meetings throughout 2022 and 2023.
With the 500 million and the 2.5 billion cell dose cohort data in mid-2022. With three new sites recently opened in the trial, we're preparing for the 5-7.5 billion cell dose cohort using only two fractions following completion of the 2.5 billion cell dose cohort later this quarter. Finally, we plan to initiate our first human trial with the MuSK- CAART in 2022, subject to IND clearance by FDA. On behalf of the entire Cabaletta crew, I appreciate your attention and would be glad, Chris, to take any questions at this point.
Great. Thank you, Steven. I appreciate it. Well, listen, as we, you know, wait for questions to come in from the audience, maybe we can turn briefly to the recently announced initial data readout. How are you thinking about it? Are you disappointed? Just love to hear your thoughts on that.
Yeah. Well, thanks for the question. You know, when we launched the company, nobody knew if CART19-related technologies would cause significant safety issues in autoimmune patients. We designed a trial that has a tremendous dose range. We started with a 20 million cell dose cohort. The reason we chose 20 million cells is not because we thought it would be effective, but because it was the lowest possible dose to manufacture reliably when you were giving a 1% infusion on the first day to each patient in that cohort. That would be 200,000 cells which needed to be reliably manufactured and administered, a very tiny dose in cell therapy. We started with a 20 million cell dose cohort, and we designed the trial initially to go to 2.5 billion cells.
With the experience in the 20 million, and now the data on both safety in the 20-500 million cohorts and biologic activity being absent in the first two cohorts, we now have more insight into a number of things. Number one, we believe that the platform is going to continue to be as safe as it currently appears. We're running the trial to determine if that's true, but we are, we have reason to be hopeful based on the early data. Therefore, we can, as we did back in, the summer of 2021, turn our attention primarily to achieving the full, efficacy profile of this elegant biology.
We enter 2022, not disappointed by the findings in the first two cohorts, but enthusiastic about the opportunity to now pursue all of the options that are at our disposal to realize the full potential of the platform. Sure, it would have been, you know, nirvana to have a dose that was selected only because it was the lowest possible dose to manufacture, deliver some biologic activity. It would have been unexpected to see such a finding, but possible in the 100 million cohort. To say we were disappointed.
No, I would say we were encouraged, frankly, by the continued safe profile, the excellent execution, and the engagement of physicians and patients, which continues as strong as ever today, to execute this trial in a way that we fully explore the opportunity to deliver, really transformative, treatment options and really a leap forward for many patients with autoimmune diseases, and perhaps even curative responses. We're looking forward to 2022. We believe we have a full portfolio of opportunities that have long been in the planning. Post the data release in December, frankly, inside the company, nothing's really changed. We're pushing forward with the plan to fully explore this platform, to fully explore the opportunity in the DesCAARTes trial and to deliver on the promise of this biologic platform.
Great. Thank you. Maybe thinking a little bit more about heading into the future, you know, as you look at your financing strategy, on a go-forward basis, you know, with roughly $120 million in the bank, I believe about $10 million spent per quarter, how are you thinking about potential strategic partnerships, maybe with pharmaceutical companies, cell therapy, autoimmune disease players in the space?
Thanks for the question. I think the first point I'd like to make is we have a tremendous financial flexibility. We designed the company from inception with our co-founding investors to be as capital efficient as possible. Our partnership on manufacturing with the University of Pennsylvania with CHOP, subsequently with WuXi and Oxford Biomedica, provide a remarkably flexible and low-cost approach to manufacturing in cell therapy for the company. We've also been, I think, very responsible, very diligent in how we both hire and focus our resource allocation.
As we come into 2022 with $120 million in cash at the end of the third quarter of last year, knowing that we spent about $10 million a quarter for the past period of time, and knowing that we've guided that we will have cash that takes us at least through the first quarter of 2023, you can imagine, and we've said frequently, we have a lot of financial flexibility. That said, the opportunities and the financing strategy again remains unchanged from what it has been over the past couple of years, and that is to execute on the platform.
We believe that we will deliver on the biologic activity of the platform, and when we do, the many interested cell therapy and autoimmune disease pharmaceutical and biotech companies that continue since inception to express interest in following and understanding our data and in understanding the potential of this disruptive platform, that remains. It's an opportunity that, at the right moment, could play a role in our financing strategy. For the early part of 2022, our focus is, continues to be on excellent execution, timely delivery of data, and efficient use of the capital that we have to make sure that we get all of the efficacy that we can out of this biologic profile.
Makes a lot of sense. Thank you, Steven. Well, listen, I don't believe that we're seeing any other questions coming in live from the audience. I do wanna say it's been a pleasure hearing from you today. Would like to maybe turn it back over to you just for any final comments. You know, look forward to speaking with you again soon.
Yeah, same here, Chris. You know, in closing, we are really enthusiastic about the opportunity to fully explore the potential safety and efficacy profile of DSG3-CAART, as well as to move MuSK myasthenia gravis into the clinic, pending the IND acceptance by FDA in 2022. Again, appreciate the opportunity to share our story this morning. Thanks so much.
Thank you.