Executive Summary / Key Takeaways

• Strategic Pipeline Focus: Cullinan Therapeutics employs a "modality-agnostic" approach, concentrating on high-impact targets in oncology and autoimmune diseases with a diversified portfolio of clinical-stage assets, including promising T-cell engagers and a selective EGFR inhibitor.
• Key Catalysts on Horizon: The company anticipates significant data readouts for CLN-978 (SLE, RA) in Q4 2025 and H1 2026, and CLN-49 in Q4 2025. Crucially, its co-developed asset, zipalertinib, is slated for a New Drug Application (NDA) submission by Taiho by the end of 2025, following positive Phase 2b results.
• Differentiated Technology Driving Potential: Cullinan's pipeline features novel technologies like CLN-978, a CD19xCD3 bispecific T-cell engager engineered for high affinity and deeper B-cell depletion, and velinotamig, a BCMAxCD3 bispecific T-cell engager with superior target selectivity, positioning them as potential best-in-class therapies.
• Solid Liquidity and Cash Runway: With $510.9 million in cash, cash equivalents, and investments as of June 30, 2025, Cullinan has reiterated guidance for a cash runway extending into 2028, providing a strong financial foundation to advance its clinical programs.
• Disciplined Portfolio Management: Recent strategic decisions, such as the in-licensing of velinotamig and the discontinuation of CLN-418 and CLN-619 in certain indications, demonstrate a commitment to optimizing resource allocation and focusing on the most promising assets.

Setting the Stage: Precision Medicine in a Dynamic Landscape

Cullinan Therapeutics, Inc., established in Cambridge, Massachusetts in 2016, is a clinical-stage biopharmaceutical company dedicated to establishing new standards of care for patients suffering from autoimmune diseases and cancer. The company's overarching strategy is fundamentally "modality-agnostic," prioritizing the identification of high-impact disease targets before selecting the most optimal therapeutic modality. This approach has allowed Cullinan to cultivate a diversified pipeline, sourcing innovation both internally and through strategic external collaborations, with a keen eye on novel technologies and differentiated mechanisms of action.

The biopharmaceutical industry is characterized by intense competition and rapid innovation, particularly in oncology and autoimmune disorders. In the autoimmune space, T-cell engagers are emerging as a "next wave of innovation," offering the potential for precise, disease-modifying interventions. Similarly, in oncology, specific genetic mutations, such as EGFR exon 20 insertion mutations (EGFR ex20ins) in non-small cell lung cancer (NSCLC), represent significant unmet needs, with a notable "lack of oral targeted therapies" for these patient populations. Cullinan's strategy directly addresses these high-value areas, positioning itself to capture significant market opportunities through targeted therapeutic development.

Technological Edge: Differentiated Mechanisms for High-Impact Targets

Cullinan's foundational strength lies in its innovative technological platforms, particularly its bispecific T-cell engagers and selective small molecules. These technologies are designed to offer distinct advantages over existing or developing therapies:

• CLN-978: A Potent CD19xCD3 Bispecific T-Cell Engager: This wholly-owned asset is engineered for "very high affinity binding to CD19 to efficiently target B cells, including those with very low CD19 levels." Its small molecular size (65 kDa) and a single-domain antibody binding to human serum albumin contribute to an extended serum half-life, enhancing its therapeutic profile. Clinically, CLN-978 is positioned to offer "deeper B cell depletion than existing therapies," a critical advantage in autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's disease (SjD). The "off-the-shelf access and convenient subcutaneous dosing" further enhance its potential for patient accessibility and treatment flexibility, distinguishing it from more complex or intravenously administered therapies. It is also notably the "only CD19-targeting T cell engager advancing a global regulatory development plan that includes a U.S. FDA-cleared IND."

• Velinotamig: A BCMAxCD3 Bispecific T-Cell Engager: Recently in-licensed from Genrix Bio, velinotamig is designed with "high affinity for BCMA and lower affinity for CD3." This crucial affinity differential, where BCMA affinity is "two orders of magnitude higher than for CD3," ensures efficient T-cell recruitment and activation against BCMA-expressing cells while minimizing non-specific T-cell activation and reducing potential toxicity. This precise targeting mechanism has already demonstrated "potential best-in-class efficacy at the Phase 2 target dose in nearly 50 patients with relapsed/refractory multiple myeloma," underscoring its therapeutic promise as it pivots to autoimmune indications.

• Zipalertinib (CLN-081/TAS6417): A Selective EGFR Inhibitor: Co-developed with Taiho Pharmaceutical, zipalertinib is an "orally-available small-molecule, irreversible EGFR inhibitor" specifically "designed to selectively target cells expressing EGFR exon 20 insertion mutations... with relative sparing of cells expressing wild-type EGFR." This selectivity is a significant differentiator, aiming to reduce off-target toxicities commonly associated with less selective EGFR inhibitors, thereby improving the therapeutic index for patients with EGFR ex20ins NSCLC. Its "Breakthrough Therapy Designation from the FDA" further highlights its potential to address a critical unmet need.

These technological differentiators form the bedrock of Cullinan's competitive moat, enabling the company to pursue therapies with potentially superior efficacy, improved safety profiles, and enhanced patient convenience. This focus on innovation is critical for carving out market share and driving long-term value in highly competitive therapeutic areas.

Strategic Evolution and Pipeline Momentum

Cullinan's journey since its 2016 inception has been marked by a disciplined approach to pipeline development and strategic capital allocation. The company's initial funding efforts and intellectual property building culminated in its first significant revenue of $18.94 million in 2021 from a license agreement. A pivotal moment occurred in 2022 with the sale of its equity interest in a zipalertinib development subsidiary to Taiho for $275.00 million, a move that provided substantial capital while retaining a co-development stake in the promising oncology asset. The rebranding from Cullinan Oncology to Cullinan Therapeutics in April 2024 underscored a strategic expansion beyond pure oncology into autoimmune diseases.

Recent operational highlights demonstrate significant momentum across its diversified pipeline:

• Zipalertinib's Path to Market: The co-development with Taiho for zipalertinib in EGFR ex20ins NSCLC has reached a critical juncture. In January 2025, the pivotal Phase 2b portion of the REZILIENT1 trial met its primary endpoint of overall response rate in previously treated patients. This success paves the way for Taiho's planned New Drug Application (NDA) submission by the end of 2025, a major value inflection point. Further data from the REZILIENT2 cohort, exploring zipalertinib in uncommon EGFR mutations and active brain metastases, are anticipated in September and October 2025, respectively. Taiho also expects to complete enrollment for the global Phase 3 REZILIENT3 trial, evaluating zipalertinib as a first-line treatment, in the first half of 2026.

• Expanding Autoimmune Footprint with CLN-978: CLN-978, a wholly-owned asset, is rapidly advancing in autoimmune diseases. It has received U.S. FDA IND clearance for Sjögren's disease (SjD) and European Medicines Agency (EMA) approval for a Phase 1 trial in rheumatoid arthritis (RA). The global Phase 1 trial in systemic lupus erythematosus (SLE) is actively enrolling, with initial safety and B-cell depletion data expected in Q4 2025. Initial clinical data from the RA trial are anticipated in H1 2026. This broad development across multiple indications for CLN-978 highlights its versatility and potential to address significant unmet needs in chronic autoimmune conditions.

• Strategic In-licensing of Velinotamig: In June 2025, Cullinan further bolstered its autoimmune pipeline by in-licensing velinotamig, a BCMAxCD3 bispecific T-cell engager, from Genrix Bio for an upfront fee of $20.00 million. This strategic addition complements CLN-978, allowing Cullinan to target a broader range of autoimmune diseases, particularly those driven by long-lived plasma cells. Genrix plans to initiate a Phase 1 clinical trial in China for autoimmune diseases by the end of 2025, with Cullinan intending to leverage this data to accelerate global clinical development.

• Disciplined Portfolio Optimization: Cullinan has demonstrated a commitment to efficient resource allocation through strategic discontinuations. In August 2024, CLN-418 development was terminated, and rights returned to Harbour BioMed US Inc., to focus resources on more promising candidates. Similarly, in May 2025, development of CLN-619 in gynecological cancers was discontinued as preliminary results did not meet internal advancement thresholds, allowing for a sharper focus on its ongoing evaluation in NSCLC and multiple myeloma.

Financial Performance and Robust Liquidity

As a clinical-stage biopharmaceutical company, Cullinan Therapeutics currently generates no product revenue, and its financial performance is characterized by significant investment in research and development. For the six months ended June 30, 2025, the company reported a net loss of $118.56 million, an increase from $79.37 million in the same period of 2024. This expanded loss is primarily attributable to a substantial increase in research and development (R&D) expenses, which rose to $102.49 million for the first six months of 2025, up from $66.91 million in the prior year period.

The surge in R&D expenses reflects the accelerated advancement and strategic expansion of Cullinan's pipeline. A notable driver was the $20.00 million upfront license fee paid for velinotamig in June 2025. Beyond this one-time payment, clinical costs increased by $9.70 million, personnel costs by $5.60 million due to additional headcount, equity-based compensation by $1.10 million, and chemistry, manufacturing, and controls costs by $0.80 million. These increases were partially offset by a $1.90 million decrease in preclinical costs, indicating a shift towards later-stage clinical development. General and administrative (G&A) expenses also saw an increase, reaching $28.31 million for the six months ended June 30, 2025, up from $26.11 million, driven by higher professional and legal fees. Interest income, a component of other income, decreased by $1.40 million due to lower investment income.

Despite these operating losses, Cullinan maintains a strong liquidity position. As of June 30, 2025, the company held $265.50 million in cash, cash equivalents, and short-term investments, supplemented by $245.40 million in long-term investments and interest receivable, totaling approximately $510.9 million. This robust cash position is critical for funding ongoing and planned clinical development. Management has provided concrete guidance, reiterating that these cash resources are expected to be sufficient to fund operations into 2028 based on its current operating plan.

While operating cash flow for the six months ended June 30, 2025, was negative $100.76 million, the company's substantial cash reserves, bolstered by past equity financings including a $262.70 million private placement in April 2024, underpin its financial stability. An at-the-market (ATM) equity offering program, with $85.60 million remaining as of June 30, 2025, provides additional financial flexibility, though no sales were made under the ATM in the first half of 2025.

Competitive Landscape and Strategic Positioning

Cullinan Therapeutics operates within a highly competitive biopharmaceutical landscape, facing established giants like Merck & Co., Inc. (MRK), Bristol-Myers Squibb Company (BMY), Pfizer Inc. (PFE), and Amgen Inc. (AMGN), as well as numerous smaller, specialized biotechs. These larger competitors possess significant advantages in global scale, extensive distribution networks, diversified product portfolios, and robust cash flow generation from commercialized products. For instance, Merck & Co., Inc. consistently demonstrates strong profitability margins and cash flow from its oncology blockbusters, while Pfizer Inc. leverages its vast R&D capabilities and global manufacturing.

However, Cullinan strategically differentiates itself through a focused, agile approach to innovation and its highly specialized technological platforms. While larger rivals may have broader market presence and financial muscle, Cullinan's "modality-agnostic" strategy allows for a more concentrated R&D effort on niche, high-impact targets where its differentiated technologies can offer a significant edge.

• Targeted Innovation vs. Broad Portfolios: Cullinan's pipeline assets, such as CLN-978 and velinotamig, are designed with specific mechanisms to achieve superior efficacy and safety profiles in defined patient populations. For example, CLN-978's potential for "deeper B cell depletion than existing therapies" directly addresses a critical unmet need in autoimmune diseases where many patients are refractory to current treatments. This specialized focus allows Cullinan to potentially achieve faster development cycles and greater R&D efficiency for these niche therapies compared to the broader, more complex operations of a Merck or Pfizer.

• Zipalertinib's Niche Advantage: In the EGFR ex20ins NSCLC market, zipalertinib's selective targeting aims to fill a void where there is a "lack of oral targeted therapies." This precision could translate into a competitive advantage by offering a better therapeutic option for a genetically defined subset of patients, potentially leading to strong market adoption upon approval.

• Vulnerabilities and Strategic Responses: Cullinan's smaller scale inherently leads to higher operational costs relative to its revenue and a greater dependence on successful clinical trial outcomes. This contrasts sharply with the financial resilience and diversified revenue streams of its larger competitors. However, Cullinan mitigates these vulnerabilities through strategic partnerships, such as the co-development agreement with Taiho for zipalertinib and the in-licensing deal with Genrix for velinotamig. These collaborations provide access to additional development expertise and financial resources, allowing Cullinan to advance its pipeline without solely bearing the full financial burden and risk. The company's disciplined portfolio management, including the discontinuation of programs that do not meet internal thresholds, further underscores its commitment to optimizing resource allocation and maximizing the potential return on its R&D investments.

The biopharmaceutical industry also faces evolving trends, such as the increasing role of artificial intelligence (AI) in drug discovery. While larger players like Bristol-Myers Squibb Company and Amgen Inc. may have greater resources to invest in cutting-edge AI platforms, Cullinan's focused R&D and strategic collaborations could allow it to leverage these advancements efficiently, potentially accelerating its own discovery efforts. Regulatory barriers and the high cost of R&D remain significant barriers to entry, which, while challenging for Cullinan, also protect its innovative therapies from rapid commoditization once approved.

Risks and Forward Outlook

While Cullinan's pipeline holds significant promise, investors must consider the inherent risks associated with clinical-stage biopharmaceutical companies. The company has a history of significant operating losses and negative cash flows, and its future viability hinges on the successful outcome of its research and development activities, regulatory approvals, and eventual commercialization of its product candidates. There is no guarantee that additional funding, beyond its current runway, will be available on acceptable terms or at all, which could force delays or termination of programs.

Global economic conditions, including trade policies and supply chain dynamics, also pose potential risks, though they have not materially impacted the business to date. Furthermore, a recent development is Cullinan's reclassification as a "smaller reporting company" effective December 31, 2025. This change, while offering reduced reporting requirements, could potentially make its common stock less attractive to some investors, leading to a less active trading market and increased stock price volatility.

The company is also evaluating the impact of the U.S. budget reconciliation bill enacted in July 2025, which includes significant changes to income tax laws, the financial effect of which is not yet available.

Despite these risks, the forward outlook is punctuated by several near-term catalysts. The anticipated NDA submission for zipalertinib by the end of 2025 is a critical milestone that could validate years of R&D investment. The upcoming data readouts for CLN-978 in SLE (Q4 2025) and RA (H1 2026), as well as for CLN-49 (Q4 2025), offer further opportunities for value creation and pipeline validation. The strategic in-licensing of velinotamig, with Genrix initiating a Phase 1 trial in China by year-end 2025, sets the stage for accelerated global development of another potential best-in-class T-cell engager. Cullinan's robust cash runway into 2028 provides the necessary financial stability to pursue these ambitious clinical and regulatory objectives.

Conclusion

Cullinan Therapeutics stands at a pivotal juncture, embodying a compelling investment thesis centered on strategic pipeline evolution and targeted innovation. The company's modality-agnostic approach, coupled with its focus on differentiated technologies like its bispecific T-cell engagers and selective EGFR inhibitor, positions it to address significant unmet medical needs in both oncology and autoimmune diseases. With key clinical and regulatory milestones on the horizon, particularly the zipalertinib NDA submission and multiple data readouts for CLN-978 and CLN-49, Cullinan is poised for potential value inflection.

While operating losses are a natural characteristic of a clinical-stage biopharmaceutical company, Cullinan's strong liquidity and projected cash runway into 2028 provide a solid foundation for executing its ambitious development plans. The company's disciplined portfolio management, including strategic in-licensing and program discontinuations, underscores its commitment to optimizing resource allocation. In a competitive landscape dominated by larger players, Cullinan's strength lies in its ability to innovate with precision, leveraging its technological advantages to carve out valuable niches. Investors should closely monitor the upcoming catalysts and the continued execution of its strategic pipeline, as these will be critical determinants of Cullinan Therapeutics' long-term success and its ability to deliver transformative therapies to patients.