Executive Summary / Key Takeaways

• Cellectis is poised for a pivotal period, advancing its lead allogeneic CAR-T candidates, lasme-cel (UCART22) and eti-cel (UCART20x22), towards later-stage clinical development, with a clear regulatory path for lasme-cel's Phase II trial initiation in H2 2025.
• A robust cash position of $230 million as of June 30, 2025, bolstered by a significant $140 million equity investment from AstraZeneca , provides a runway into H2 2027, explicitly covering pivotal study costs and reflecting prudent financial management.
• The company's proprietary TALEN gene-editing technology and in-house manufacturing capabilities are key differentiators, with the UCART22-P2 product demonstrating superior potency, underpinning the potential for enhanced clinical outcomes and a competitive edge.
• Strategic collaborations, particularly with AstraZeneca across multiple cell and gene therapy programs, and the ongoing Servier arbitration, represent significant potential for non-dilutive funding and validation of Cellectis' platform.
• Cellectis is strategically positioning its dual-targeting eti-cel (UCART20x22) as a non-CD19 alternative for relapsed/refractory NHL, addressing a critical unmet need and differentiating itself in a competitive landscape increasingly focused on orthogonal targets.

Cellectis' Gene-Editing Vision and Market Position

Cellectis S.A., a clinical-stage biotechnology firm established in 1999 and headquartered in Paris, France, stands at the forefront of gene-editing innovation, dedicated to developing life-saving allogeneic chimeric antigen receptor T-cell (CAR-T) and gene therapies. The company's foundational strategy revolves around its proprietary TALEN gene-editing platform, which enables the precise engineering of T-cells for off-the-shelf cancer treatments. This approach aims to overcome the logistical and manufacturing complexities associated with autologous CAR-T therapies, offering a more accessible and scalable solution for patients with hard-to-treat cancers.

The company's journey has been marked by strategic evolution, including securing a €40 million credit facility from the European Investment Bank (EIB), with the final tranches drawn in 2024, providing crucial financial backing for its ambitious pipeline. A transformative period unfolded in late 2023 and early 2024 with a major strategic collaboration and investment agreement with AstraZeneca . This partnership, initiated with an initial $105 million investment and followed by an additional $140 million equity investment completed by May 3, 2024, solidified AstraZeneca's position as a significant shareholder, owning approximately 44% of Cellectis' share capital and 30% of voting rights. This strategic alignment not only injected substantial capital but also validated Cellectis' technological prowess and expanded its research horizons into new therapeutic areas.

Technological Differentiation and Innovation

Cellectis' core competitive advantage lies in its proprietary TALEN gene-editing technology. This platform allows for highly precise and efficient genetic modifications, which are crucial for engineering allogeneic CAR-T cells that can be administered to multiple patients without triggering graft-versus-host disease. The tangible benefits of this technology are evident in the performance of its in-house manufactured product, UCART22-P2, which has demonstrated significantly more potency compared to its predecessor, UCART22-P1, manufactured by an external CDMO. This enhanced potency, particularly in terms of translational data related to cell expansion, is considered "unmatched" by management, suggesting a superior therapeutic profile. For investors, this translates into the potential for improved efficacy, a stronger competitive moat, and ultimately, better market positioning and financial performance through higher adoption rates and potentially premium pricing.

The company's R&D initiatives are further bolstered by its collaboration with AstraZeneca , which encompasses three active programs: one allogeneic CAR-T for hematological malignancies, one for solid tumors, and one in vivo gene therapy for a genetic disorder. These programs leverage the breadth and depth of Cellectis' platform, with AstraZeneca fully funding the associated research costs. This strategic arrangement not only accelerates the development of novel genomic medicines but also significantly offsets Cellectis' internal R&D expenditures, thereby extending its cash runway. Additionally, Cellectis' innovation team continues to explore advanced CAR-T strategies, including those targeting solid tumors and overcoming immunosuppressive microenvironments, with preclinical data presented at major scientific conferences and published in peer-reviewed journals. The company also maintains a licensing agreement with Iovance Biotherapeutics (IOVA), which utilizes Cellectis' TALEN platform for its PD-1 inactivated TIL therapy, IOV-4001, currently in Phase I for melanoma and non-small cell lung cancer.

Competitive Landscape and Strategic Positioning

Cellectis operates within a dynamic and highly competitive biotechnology landscape, primarily vying with other clinical-stage companies developing allogeneic and autologous CAR-T therapies, as well as broader gene-editing platforms. Key direct competitors include Allogene Therapeutics , CRISPR Therapeutics , Editas Medicine , and Bluebird Bio (BLUE).

Cellectis differentiates itself through its allogeneic, off-the-shelf CAR-T approach and its proprietary TALEN gene-editing technology. While Allogene Therapeutics also focuses on allogeneic CAR-T, Cellectis emphasizes its unique product positioning, particularly for very late-stage indications, and its use of actual alemtuzumab for lymphodepletion, which management believes is critical for improved responses and has a favorable risk-benefit profile compared to Allogene's ALLO-647. This distinction is crucial, as the efficacy and safety of lymphodepletion regimens are paramount in CAR-T therapy.

Against CRISPR Therapeutics (CRSP) and Editas Medicine (EDIT), which are pioneers in broader CRISPR-based gene editing, Cellectis' competitive edge lies in its specialized focus on T-cell engineering for oncology. While CRISPR platforms offer technological breadth, Cellectis' tailored therapies aim for superior targeting and potentially faster therapeutic responses in specific cancer applications. The company's strategic alliances, particularly with AstraZeneca , also provide a broader market reach and enhanced capital efficiency, contrasting with some competitors' more internal development focus.

A significant competitive dynamic is the market for non-CD19 CAR-T therapies. The discontinuation of CARGO (CRGX)'s CD22-targeted autologous asset, despite showing efficacy, highlighted challenges with durability and a high-grade toxicity profile. Cellectis views this as an "opening up an avenue for a non-19 CAR T assets", which it aims to capture with its dual-targeting eti-cel (UCART20x22). This product, targeting CD20 and CD22, is strategically positioned to address patients who have failed CD19 therapies, offering an "off-the-shelf alternative that does not target 19". This differentiation is particularly relevant as CD19 therapies become entrenched in earlier lines of treatment, creating a strong need for orthogonal targets.

Clinical Pipeline Momentum: Advancing Allogeneic CAR-T

Cellectis' core investment thesis is deeply intertwined with the successful progression of its wholly-owned clinical pipeline, primarily lasme-cel (UCART22) and eti-cel (UCART20x22). The company has made significant strides in advancing these programs, demonstrating a clear commitment to bringing these potentially life-saving therapies to patients with high unmet medical needs.

Lasme-cel (UCART22) in Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (ALL)

Lasme-cel, Cellectis' lead product candidate, is being developed for relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), a devastating disease with limited treatment options, especially for patients who have relapsed after multiple prior lines of therapy, including CD19 bispecifics or autologous CAR-T. The program has achieved critical regulatory milestones, completing end of Phase I discussions with both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in July 2025. These interactions have provided a "clear path" to commence a pivotal Phase II trial in the second half of 2025. Regulatory authorities have shown broad support, agreeing on endpoints, statistical plans, and the size of the safety database required for a Biologics License Application (BLA).

Cellectis plans to host an Investors R&D Day on October 16, 2025, in New York City, to present the full Phase I data set for lasme-cel, including safety, efficacy, and durability data from all dosed patients, with a particular focus on those at the recommended Phase II dose. The company will also outline its late-stage development strategy, including the Phase II design, patient population, and path to BLA. Recruitment for the pivotal Phase II study is expected to begin by the end of 2025, with additional trial sites being established in the United States and Europe to accelerate accrual. The regulatory authorities have also provided clear guidance on the approach to ensure adequate data for registration, including a commitment to a 15-year follow-up for patients, though the primary analysis will focus on a shorter-term surrogate endpoint. UCART22 has also received Orphan Drug Designation and Rare Pediatric Disease designation from the FDA, and Orphan Drug Designation from the European Commission, underscoring its potential and the significant unmet need it addresses.

Eti-cel (UCART20x22) in Relapsed/Refractory Non-Hodgkin Lymphoma (NHL)

Eti-cel, a dual CAR-T asset targeting CD20 and CD22, is progressing in the NatHaLi-01 study for relapsed or refractory non-Hodgkin lymphoma. This program addresses an important unmet need for patients who have relapsed after previous lines of therapy, including autologous CD19 CAR-T. The dual-targeting strategy is a key differentiator, as it avoids targeting CD19, which is increasingly saturated by existing therapies. This positions eti-cel as a valuable "off-the-shelf alternative" for physicians seeking to "alternate the targets" after CD19 failure.

Cellectis anticipates presenting Phase I data and outlining its late-stage development strategy for eti-cel late in 2025, with a transition to Phase II preparation expected in 2026. The company is actively expanding clinical trial sites to accelerate recruitment for this program. While the patient numbers for the eti-cel data set are expected to be smaller than for lasme-cel due to its earlier stage of development, the program holds significant promise in a market segment demanding non-CD19 options.

Strategic Prioritization

In a strategic move to optimize resource allocation, Cellectis de-prioritized the development of UCART123 (AMELI-01 trial) for relapsed/refractory acute myeloid leukemia. This decision, while acknowledging promising early signals, was driven by a commitment to "prioritize the assets that we believe gave us the highest chance of success" and to "optimize our runway". This focused approach ensures that capital and efforts are concentrated on the lead programs, lasme-cel and eti-cel, which are deemed to have the most immediate and impactful path to market.

Strategic Partnerships: Fueling Growth and Innovation

Cellectis' strategic partnerships are integral to its growth trajectory, providing both financial stability and expanded research capabilities. These collaborations validate the company's gene-editing platform and extend its reach into diverse therapeutic areas.

AstraZeneca Collaboration

The collaboration with AstraZeneca is a cornerstone of Cellectis' strategy. This joint research and collaboration agreement encompasses up to 10 cell and gene therapy programs, with three already initiated: one allogeneic CAR-T for hematological malignancies, one for solid tumors, and one in vivo gene therapy for a genetic disorder. AstraZeneca's substantial equity investments, totaling $245 million, underscore its confidence in Cellectis' technology and long-term vision. Beyond the upfront payments and development milestones, AstraZeneca fully reimburses Cellectis for research costs incurred under the collaboration, significantly offsetting Cellectis' R&D expenses and contributing to its extended cash runway. This partnership not only provides non-dilutive funding but also leverages AstraZeneca's expertise to accelerate the development of next-generation genomic medicines.

Servier/Allogene Arbitration

Cellectis is currently engaged in an arbitration with Servier, and its sublicensee Allogene , before the Paris Mediation and Arbitration Center. This action was initiated in September 2022 following Servier's decision to cease development of licensed CD19 products. Cellectis is seeking termination of the agreement, fair compensation for losses incurred due to the lack of development, and payment of due milestones. The arbitral decision is anticipated on or before December 15, 2025. While the outcome is uncertain, a favorable decision could provide a significant non-dilutive cash inflow, with Cellectis eligible for up to $410 million in milestones and low double-digit royalties for cema-cel (ALLO-501A).

The broader implications of this situation also touch upon Allogene's progress with cema-cel. Allogene is pursuing a strategy to "leapfrog autologous CD19 CAR T in the second line, by going straight into first line consolidation" with its ALPHA3 trial. Recent long-term data from Allogene's ALPHA/ALPHA2 trials, demonstrating durable responses out to four years, are seen as highly encouraging, potentially removing an "overhang around durability of the assets" for allogeneic CAR-T therapies. This success, if replicated in ALPHA3, could further validate the allogeneic CAR-T platform, benefiting Cellectis through its licensing agreement.

Financial Performance and Outlook: A Strengthened Foundation

Cellectis' financial position has been significantly strengthened, providing a solid foundation for its ambitious clinical development plans.

As of June 30, 2025, the company reported cash, cash equivalents, restricted cash, and fixed-term deposits totaling $230 million. This represents a decrease of $33.2 million from $264 million as of December 31, 2024, primarily due to operational expenditures, including $23.2 million in payments to suppliers and $23.6 million in wages, bonuses, and social expenses. These outflows were partially offset by $13.4 million from revenue and $5.1 million in interest income.

Crucially, this cash position is projected to fund operations into the second half of 2027. This guidance explicitly includes the full costs associated with the pivotal studies for both lasme-cel and eti-cel, demonstrating management's confidence in its ability to finance these critical development phases. The company has adopted a conservative approach to its cash runway projections, "severely discounting any cash in we may receive from our partners, including Servier and Allogene ". This conservative stance suggests potential for upside if arbitration outcomes or additional milestones materialize.

From a profitability perspective, as a clinical-stage biotechnology company, Cellectis currently operates at a loss, which is typical for companies in this phase of development. The latest TTM (trailing twelve months) figures indicate a Gross Profit Margin of 92.11%, an Operating Profit Margin of -80.32%, and a Net Profit Margin of -104.80%. These figures reflect the substantial R&D investments required to advance its pipeline. The Debt/Equity ratio stands at 0.98, indicating a manageable level of debt relative to equity. The strategic decision to de-prioritize UCART123 was a direct measure to optimize cash utilization and extend the runway, underscoring a disciplined approach to financial management.

Risks and Challenges

Despite the promising outlook, Cellectis faces several inherent risks common to the biotechnology sector. The outcome of the Servier arbitration, expected by December 15, 2025, remains a significant uncertainty. While Cellectis is seeking termination of the agreement and compensation, the decision could vary, impacting potential non-dilutive funding.

Clinical development risks are paramount. While lasme-cel has a "clear path" to Phase II, success in pivotal trials is never guaranteed, and data from Phase II will ultimately dictate the path to registration. Similarly, the progression of eti-cel to Phase II is contingent on Phase I data assessment. Any unexpected safety signals or efficacy concerns could delay or halt development.

Competitive pressures are intense. While Cellectis differentiates its allogeneic CAR-T products, particularly eti-cel as a non-CD19 option, the landscape is rapidly evolving with other players advancing their own allogeneic and autologous therapies. Maintaining a technological edge and demonstrating superior durability and safety will be critical.

Finally, the manufacturing and lymphodepletion regimen for allogeneic CAR-T therapies present specific challenges. Cellectis' reliance on alemtuzumab for lymphodepletion, while believed to be critical for responses, requires careful management of potential infection risks through mandatory prophylaxis and risk mitigation strategies. The company's confidence in its approach, contrasting with Allogene's (ALLO) decision to move away from CD52 lymphodepletion, highlights the nuanced considerations in this area.

Conclusion

Cellectis stands at a pivotal juncture, transitioning its lead allogeneic CAR-T programs into later-stage clinical development with a strengthened financial foundation and robust strategic partnerships. The company's proprietary TALEN gene-editing technology and in-house manufacturing capabilities provide a distinct competitive advantage, particularly with the demonstrated potency of its UCART22-P2 product. The clear regulatory pathway for lasme-cel's pivotal Phase II trial and the strategic positioning of eti-cel as a non-CD19 alternative underscore a focused and promising pipeline.

The substantial investment from AstraZeneca (AZN) and the extended cash runway into H2 2027 provide critical resources to execute on these ambitious plans, while the ongoing Servier arbitration represents a potential upside for non-dilutive funding. While inherent clinical development risks and competitive pressures remain, Cellectis' commitment to innovation, disciplined resource allocation, and strategic collaborations position it as a compelling player in the evolving landscape of cell and gene therapies. Investors will closely monitor the upcoming R&D Day for lasme-cel, the eti-cel data readout, and the Servier arbitration decision as key indicators of the company's trajectory towards delivering paradigm-shifting treatments for patients.