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Cabaletta Bio (NASDAQ:CABA) fast making headway with its lead asset CABA-201 for the treatment of patients with autoimmune disorders. This is a CD-19 CAR-T therapy being used for the treatment of patients with lupus nephritis [SLE of the kidney] and non-renal SLE as well. What makes this company unique would be its approach of attaching a 4-1BB co-stimulatory domain to the drug to enhance efficacy. The main form of the technology is known as Chimeric Antigen Receptor T cells for Autoimmunity [CARTA]. The goal is to go after SLE first, however, other autoimmune indications being explored are: Myositis, systemic sclerosis, and generalized myasthenia gravis, plus many more. Matter of fact, Cabaletta is already in the process of conducting four phase 1/2 studies using CABA-201 to treat patients with SLE, myositis, systemic sclerosis, and generalized myasthenia gravis [gMG].
It is believed that its platform can deplete B-cells entirely and possibly reset the immune system. This remains to be seen but seems like a good approach. The thing to note is that the company is going to start off using only a lower starting dose of 1 X 10^6 cells/kg. The two phase 1/2 studies to focus on are those using CABA-201 for the treatment of patients with systemic lupus erythematosus [SLE] and myositis, respectively. Why is that? That’s because these two indications are going to provide two major catalysts for investors to look forward to. Results from both of these phase 1/2 studies, using CABA-201 for the treatment of these two patient populations, are expected in the 1st half of 2024. Over time, this biotech has the potential to release data from two other indications, which are systemic sclerosis [SSc] and generalized myasthenia gravis [gMG]. It is expected that results from the two other ongoing phase 1/2 studies, using CABA-201 for the treatment of patients with SSc and gMG, will be released in the 2nd half of 2024. If all goes well with clinical data, then this will set up a transformational year for the company.
CABA-201 For Treatment Of Patients With Systemic Lupus Erythematosus
involves the use of CABA-201, which is a CD-19-directed CAR-T being used to treat patients with systemic lupus erythematosus [SLE]. Another name for SLE is basically lupus as well. Before going over the ongoing phase 1/2 study, plus any catalysts to come out of it, it is important to note what lupus is and what the possible market opportunity from it could be. Lupus is a type of disorder whereby the immune system just randomly starts to attack the patient’s own tissue and organs. The other use of CABA-201 is to go after patients with lupus nephritis. In essence, this is lupus which primarily targets the kidneys of a patient. Lupus nephritis is a considerable amount of the patient population, despite only causing problems in the kidney. The reason why I state this is because it is believed that about 60% of patients with lupus move on to develop lupus nephritis [LN]. The global lupus drugs market is expected to reach $3.6 billion by 2029. This is a big market opportunity and the fact that Cabaletta might be able to target the entire lupus market [including lupus nephritis] is highly ideal.
The goal of Cabaletta Bio is to run a phase 1/2 study using CABA-201 for the treatment of patients with systemic lupus erythematosus [SLE]. The goal is to split such patients into two different cohorts. One cohort is going to be 6 patients with LN and then the other 6 patients are just going to be with lupus. The goal is to enroll 12 patients in total in this trial, who are going to be separated into this parallel cohort. The starting dose is going to be 1 X 10^6 cells/kg without a dose escalation requirement in place [can escalate dose if necessary but not required]. The primary goal of the study first and foremost with these early-stage studies is to evaluate the safety of the treatment first and foremost. As such the primary endpoint is going to look at the incident of adverse events [AEs] 28 days after infusion with CABA-201. Other measurements are going to look at pharmacodynamics [PD] and pharmacokinetics [PK] of this CAR-T. That is, the level of B-cells and T-cells in a patient’s blood will be measured, respectively. There was another highly positive development as it relates to this specific program. This is with respect to the fact that CABA-201 was given Fast Track Designation [FTD] by the FDA for the treatment of patients with SLE [lupus] and Lupus Nephritis [LN]. However, this bodes well for the program as a whole. Why is that? Well, that’s because this isn’t the first FTD given by the agency. Cabaletta Bio has also received FTD for other indications to be advanced in phase 1/2 testing, such as dermatomyositis and systemic sclerosis. The main thing here to note is that Fast Track Designation ultimately means expedited development and review of a drug. In this case, there is a possibility that CABA-201 could reach the endpoint of approval faster and could be given expedited review like 6 months instead of 12 months. With such advancement in the works, this brings up a major catalyst opportunity for investors to look forward to. It is expected that results from the phase 1/2 study, using CABA-201 for the treatment of patients with SLE, are expected in the 1st half of 2024.
Financials
According to the 10-Q SEC Filing, Cabaletta Bio had cash, cash equivalents and short-term investment of $164.4 million as of September 30th of 2023. It believed that it would have enough cash to fund its operations into Q4 of 2025. However, despite having this cash runway, it still enacted an offering to raise additional funds. It enacted an ATM Sales program, whereby it raised a total of $94 million in gross proceeds to fund its operations. By doing so though, it was able to extend its cash runway. As such, it now believes that it has enough cash on hand to fund its operations into 1st half of 2026.
This is an extensive amount of funds, but there is something to keep in mind, in spite of what this company did. It expects to report results from two of its phase 1/2 study in the 1st half of 2024 [targeting SLE and myositis] and then another two results in the 2nd half of 2024 [targeting generalized myasthenia gravis and systemic sclerosis]. If any of these studies cause the stock price to trade significantly higher, then I would say it is keen to be prepared for a possible capital raise. This is not guaranteed to happen, but keep in mind that management always takes advantage of sharp rises in the stock price.
Risks To Business
There are several risks that investors should be aware of before investing in Cabaletta Bio. The first risk to consider would be with respect to the CD19-CAR T known as CABA-201. That’s because the use of this drug is being explored in four ongoing phase 1/2 studies for the treatment of patients with several types of autoimmune disorders. However, it is only expected to report on results from the first two indications only, which are systemic lupus erythematosus [SLE] and Lupus Nephritis [LN] respectively. There is no assurance that using CD19 CAR-T CABA-201 will help treat this patient population. The technology used by this treatment is known as Chimeric Antigen Receptor T cells for Autoimmunity [CARTA]. The purpose of designing CABA-201 is to completely eliminate all B-cells in a patient. Why is that? The goal is to provide a complete entire reset of the immune system, in hopes of improving responses for these autoimmune disorders. Current treatment options only work modestly and result in broad immunosuppression. There is no assurance that such a mechanism of action will be proven in patients with SLE/LN or any other autoimmune disorder being targeted.
The second risk to consider would be with respect to the use of Chimeric AutoAntibody Receptor T [CAART] cells. That’s because the goal of these CAR-Ts is to specifically only target antigen-specific B-cells in order to help patients. There are two candidates with respect to such CAR-Ts known as desmoglein 3 chimeric autoantibody receptor T [DSG3-CAART] and muscle-specific kinase [MuSK] chimeric autoantibody receptor T [MuSK-CAART]. The goal of this other candidate is to be able to only target the disease-causing B-cells. There is no assurance that this other approach in targeting only antigen-specific B-cells will pay off and thus mean far greater durable responses for these patients.
The third and final risk to consider would be with respect to the advancement of each of the 4 ongoing studies using CABA-201 for the treatment of patients with autoimmune disorders. That’s because each study and indication is having patients all treated with a similar dose of 1 X 10^6 cell/kg. Thus, there is no dose escalation ongoing and these phase 1/2 studies are being deployed in parallel design. The risk here is that each of the 4 studies is only going to recruit 6 patients. That means even if data turns out to be positive, it must be taken with a grain of salt. Not only that, but the goal is to deploy these trials in this fashion for the reason of possibly being able to go up to the FDA to discuss regulatory trials. Thus, another risk to consider here is that even with positive data being generated, there is no guarantee that this company will be allowed to advance the use of CABA-201 towards late-stage registrational testing.
Conclusion
Cabaletta Bio has been able to make significant progress in being able to advance its pipeline. It is setting itself up for success because it has been able to advance the use of 4-1BB CD19 CAR-T CABA-201 for the treatment of several types of autoimmune disorders. This provides multiple shots on goal with respect to advancing the use of this specific CAR-T. The market opportunity I described above was only for the treatment of patients with lupus. When looking at the entire autoimmune disease patient population, it is a huge opportunity. It is expected that the global market for autoimmune disease therapeutics is expected to reach $185 billion by 2029. A good thing about this biotech is that it has been able to deploy two different types of CAR-T technologies for its pipeline. CABA-201 makes use of CARTA in order to completely deplete all B-cells and reset the immune system with a single infusion. There are two other candidates in the pipeline, which provide additional shots on goal. These would be with respect to the use of DSG3-CAART and MuSK-CAART, both of which are chimeric autoantibody receptor T-cells [CAARTs]. They are each being developed to target mucosal pemphigus vulgaris [mPV] and MuSK-associated myasthenia gravis [MG] respectively.
Both of these candidates are already in clinical testing for these specific patient populations. They are not part of the other 4 ongoing phase 1/2 studies, which are using CABA-201 to treat patients with autoimmune disorders. What is the best aspect of looking into this pharmaceutical company? I believe it is in the possibility of having a possible improved pathway to possible approval of CABA-201. The reason why I state this is because the entire program has been deployed with no need to dose escalate for starters. Not only that but the studies were designed in order to generate data that can be later discussed with the FDA for quicker advancement. Whether such a speedier approval pathway process depends upon two things, which are clinical data to be released and positive FDA feedback.
