Atara Biotherapeutics Presents Preclinical Data on ATA3219, an Allogeneic CD19-Targeted CAR T Therapy for the Treatment of B-Cell Driven Autoimmune Diseases, at the ISCT 2024 Annual Meeting
Atara Biotherapeutics has announced promising preclinical data for ATA3219, an allogeneic CD19-targeted CAR T therapy aimed at treating B-cell driven autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The data, to be presented at the ISCT 2024 Annual Meeting, show that ATA3219 effectively depletes CD19+ B-cells and induces lower levels of pro-inflammatory cytokines compared to autologous CD19 CAR T cells.
ATA3219 incorporates multiple clinically validated technologies, including a modified CD3ζ signaling domain and a less differentiated phenotype. A Phase 1 clinical trial for lupus nephritis (LN) and severe SLE without lymphodepletion is expected to begin in Q4 2024, with initial data anticipated in 2025.
- ATA3219 shows effective B-cell depletion against SLE and MS patient cells.
- Induces lower levels of pro-inflammatory cytokines compared to autologous CD19 CAR T cells.
- ATA3219 is an 'off-the-shelf' therapy, offering potential ease of use and reduced treatment complexity.
- Incorporates a modified CD3ζ signaling domain for sustained effector function.
- Preclinical findings support advancing ATA3219 to clinical evaluation.
- Initial clinical data from Phase 1 trial for NHL expected in Q4 2024.
- ATA3219's efficacy and safety still need to be validated in clinical trials.
- Initial data for LN and severe SLE without lymphodepletion not expected until 2025.
- No information on potential side effects or long-term outcomes from preclinical trials.
- Financial implications and costs associated with developing ATA3219 not discussed.
Insights
The preclinical data on ATA3219 highlights promising therapeutic potential for treating B-cell driven autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Allogeneic CAR T therapies, like ATA3219, are designed to be 'off-the-shelf' solutions, offering advantages over autologous treatments which require personalized cell extraction and modification.
One of the key findings is that ATA3219 shows a comparable cytotoxic function to existing CD19 CAR T cells but with a reduced inflammatory profile. This is significant because it addresses two major issues in CAR T-cell therapies: inflammation and toxicity. Lower levels of pro-inflammatory cytokines such as IFN-γ, TNF-α and IL-6 potentially translate to fewer adverse effects, which is a considerable advancement in patient safety and comfort. The ability to deplete B-cells effectively while reducing inflammation may also contribute to better long-term treatment outcomes.
The preclinical results support moving forward with clinical trials, particularly for lupus nephritis and severe systemic lupus erythematosus. If these trials confirm the preclinical findings, it could lead to a new paradigm in treating these debilitating conditions with a therapy that is more readily available and less personalized than current options.
Overall, the data is encouraging and warrants further investigation. For retail investors, it's important to note the potential for this therapy to address a significant unmet need in autoimmune diseases, which could drive future value for Atara Biotherapeutics.
The announcement of ATA3219’s preclinical data is very pertinent for investors as it signals potential future revenue streams. The therapy targets high-need autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis (MS), both of which represent substantial market opportunities. Should ATA3219 advance through clinical trials successfully, the market potential for a successful CAR T-cell therapy in autoimmune diseases could be substantial, given the chronic nature and the limited effective treatment options currently available.
Looking forward, the initiation of Phase 1 trials in Q4 2024 will be a critical milestone. Investors should keep an eye on these developments as positive clinical data could significantly impact Atara’s stock prices. Additionally, the 'off-the-shelf' nature of ATA3219 implies potentially lower manufacturing costs compared to autologous therapies, which could translate into higher profit margins.
However, as with any biopharmaceutical investment, there are risks. Clinical trials are inherently uncertain and the success of preclinical results does not always translate into clinical efficacy. Investors should balance the potential rewards of a breakthrough therapy against these inherent risks.
The strategic development of ATA3219 taps into a growing market segment of CAR T-cell therapies for autoimmune diseases. The shift from autologous to allogeneic CAR T-cell therapies is a significant trend in the biopharmaceutical industry, driven by the need for more accessible and scalable treatments. By positioning ATA3219 as an 'off-the-shelf' therapy, Atara Biotherapeutics is aligning itself with market demands for more efficient and cost-effective treatment solutions.
Moreover, the company’s approach addresses two critical pain points: efficacy and safety. The data showing lower levels of pro-inflammatory cytokines while maintaining cytotoxic potency is a compelling value proposition. This could make ATA3219 a preferred option over existing therapies that often come with higher toxicity and more complex administration processes.
From a market perspective, the successful development and commercialization of ATA3219 could open the doors to significant adoption in the treatment of B-cell driven autoimmune diseases. The anticipated data readouts in 2024 and 2025 will be key indicators of market viability and investor sentiment. It’s essential to monitor these timelines and the broader competitive landscape to fully gauge the potential impact on Atara’s market position.
ATA3219 Demonstrates Complete CD19-Specific B-Cell Depletion Against Systemic Lupus Erythematosus and Multiple Sclerosis Patient Peripheral Blood Mononuclear Cells
ATA3219 Induces Lower Levels of Pro-Inflammatory Cytokines While Maintaining Cytotoxic Potency Compared With Autologous Benchmark CD19 CAR T Cells
Results Support Clinical Evaluation of ATA3219, Including Initiation of Phase 1 Study in Lupus Nephritis and Severe Systemic Lupus Erythematosus Without Lymphodepletion Expected in Q4 2024
ATA3219 consists of allogeneic CD19-directed CAR EBV T cells that have been optimized to offer a potential best-in-class profile and off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that sustains potent effector function while modulating activation and inflammation; a less differentiated phenotype for robust expansion and persistence; and no modification of the endogenous T-cell receptor (no gene editing) as a key T-cell survival signal.
“Following exciting early clinical data with autologous CD19 CAR T in autoimmune patients, we believe there is an opportunity to further improve long-term efficacy, reduce toxicity and simplify treatment through our optimized allogeneic CD19 CAR T cells,” said Cokey Nguyen, Ph.D., Executive Vice President, Chief Scientific & Technical Officer at Atara. “We are pleased to share promising preclinical data that shows ATA3219 mediates robust B-cell depletion against SLE and multiple sclerosis patient derived immune cells. Importantly, ATA3219 is an off-the-shelf option that shows a favorable inflammatory profile that may lead to less toxicity and improved tolerability in the clinic. We look forward to continued evaluation of ATA3219 for the treatment of non-Hodgkin’s lymphoma, lupus nephritis, and in a recently announced cohort expansion for severe SLE without lymphodepletion.”
The ATA3219 preclinical data demonstrate potent CD19 antigen-specific cytotoxic activity against CD19+ targets in vitro and in vivo. Data highlights comparing ATA3219 to an autologous benchmark CD19 CAR T include:
- More robust central memory cell population as a result of the 1XX co-stimulatory domain and optimized manufacturing process
- Complete CAR-mediated B-cell depletion against SLE and MS patient peripheral blood mononuclear cells with comparable potency
- Reduced inflammatory profile with decreased secretion of pro-inflammatory cytokines IFN-γ, TNF-α and IL-6, as well as T helper 2 (Th2) cytokines IL-4 and IL-5, while achieving comparable B-cell depletion
These preclinical results support advancing ATA3219 towards clinical evaluation in patients with B-cell driven autoimmune diseases.
ATA3219 is currently being investigated in a Phase 1 trial (NCT06256484) for the treatment of relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) with initial clinical data expected in the fourth quarter 2024. Additionally, ATA3219 will be evaluated in a multi-center, Phase 1, open-label, single-arm, dose-escalation study for the treatment of LN with lymphodepletion and a separate cohort in severe SLE without lymphodepletion. Initial data for LN and severe SLE without lymphodepletion is anticipated in the first half and second half of 2025, respectively.
Poster Presentation Details:
Title: ATA3219: Allogeneic CD19 CAR EBV T Cells for the Treatment of B-Cell Driven Autoimmune Diseases
Presenting Author: Alfonso Brito, M.S., Preclinical & Translational Sciences, Atara Biotherapeutics, Inc.,
Date & Time: Wednesday, May 29, 2024, at 7:00 - 8:30 p.m. PDT
Poster Number: 1025
Session: Poster Networking Session 1
Location: Exhibit & Poster Hall,
About ATA3219
ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus (SLE) and lupus nephritis. ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence.
Next-Generation Allogeneic CAR T Approach
Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease. Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promote in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching. A molecular toolkit of clinically-validated technologies—including the 1XX costimulatory domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T.
About Atara Biotherapeutics, Inc.
Atara is harnessing the natural power of the immune system to develop off-the-shelf cell therapies for difficult-to-treat cancers and autoimmune conditions that can be rapidly delivered to patients from inventory. With cutting-edge science and differentiated approach, Atara is the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy. Our advanced and versatile T-cell platform does not require T-cell receptor or HLA gene editing and forms the basis of a diverse portfolio of investigational therapies that target EBV, the root cause of certain diseases, in addition to next-generation AlloCAR-Ts designed for best-in-class opportunities across a broad range of hematological malignancies and B-cell driven autoimmune diseases. Atara is headquartered in
Forward-Looking Statements
This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding the development, timing and progress of ATA3219, including the potential characteristics and benefits of ATA3219, such as the potency and ability of ATA3219 to deplete B cells, the potential characteristics and benefits of ATA3219 as compared to other products or product candidates, including autologous products and product candidates, and the timing and progress of clinical studies of ATA3219 to treat various indications, including NHL and SLE with LN (including a cohort in severe SLE without lymphodepletion) and the potential data that could be obtained from such studies. Because such statements deal with future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic and the wars in
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Investor and Media Relations
Jason Awe, Ph.D.
Senior Director, Corporate Communications & Investor Relations
(805) 217-2287
jawe@atarabio.com
Source: Atara Biotherapeutics, Inc.
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