Executive Summary / Key Takeaways

• Innate Pharma has strategically refocused its investments on three high-value clinical assets: the novel Nectin-4 ADC IPH4502, the anti-KIR3DL2 antibody lacutamab, and the partnered anti-NKG2A checkpoint inhibitor monalizumab.
• The company's proprietary IPH4502 ADC demonstrates significant technological differentiation, showing preclinical efficacy in enfortumab vedotin-resistant urothelial cancer and in tumors with low/heterogeneous Nectin-4 expression, addressing critical unmet needs.
• Lacutamab has achieved FDA Breakthrough Therapy Designation for Sézary syndrome, supported by strong Phase II data, and is advancing towards a potential accelerated approval by 2027, contingent on securing financing for its confirmatory Phase III trial.
• The partnership with AstraZeneca (AZN) for monalizumab continues to be a substantial value driver, with up to an additional $825 million in milestones and double-digit royalties, and Phase III data expected in the second half of 2026.
• With €70.4 million in cash as of June 30, 2025, Innate Pharma has a cash runway until the end of Q3 2026, enabling execution on its focused strategic priorities while actively pursuing financing options for lacutamab.

Innate Pharma's Strategic Evolution in Oncology

Innate Pharma S.A., established in 1999 in Marseille, France, has built its foundation on pioneering antibody engineering to develop life-enhancing cancer immunotherapies. The company's core business involves leveraging its scientific expertise to create first- and best-in-class antibody-based treatments. This strategy has led to a robust pipeline, including proprietary assets in early clinical stages and partnered assets spanning early to late-stage development. The biotechnology industry, characterized by high R&D costs and stringent regulatory hurdles, demands focused innovation and strategic partnerships, which Innate Pharma has actively pursued throughout its history.

A pivotal moment for Innate Pharma occurred in the first half of 2025 with a strategic decision to concentrate investments on three high-value clinical assets: IPH4502, lacutamab, and monalizumab. This refocus aims to streamline the organization and maximize impact for both patients and shareholders. This strategic pivot, coupled with a €15 million equity investment from Sanofi (SNY) in April 2025, underscores a commitment to advancing programs with the greatest potential. The company's historical journey, marked by collaborations with industry giants like AstraZeneca and Sanofi, has shaped its current position, emphasizing a blend of proprietary innovation and strategic alliances to navigate the competitive oncology landscape.

Technological Edge: Differentiated Platforms Driving Innovation

Innate Pharma's competitive advantage is significantly bolstered by its differentiated technological platforms, particularly in Antibody Drug Conjugates (ADCs) and NK Cell Engagers (ANKETs). These platforms are designed to overcome limitations of existing therapies and address high unmet medical needs.

IPH4502: A Next-Generation Nectin-4 ADC

IPH4502, Innate Pharma's lead proprietary ADC, represents a significant technological leap in targeting Nectin-4 expressing tumors. This differentiated ADC leverages a novel design, featuring a proprietary humanized antibody that binds a unique epitope on the Nectin-4 molecule. Its stable, cleavable, and hydrophilic linker ensures high ADC exposure and minimizes systemic release of the exatecan payload, thereby reducing potential side effects. Exatecan, a potent topoisomerase I inhibitor, exhibits bystander activity, impacting tumor cells with varying Nectin-4 expression levels. Crucially, it remains highly active in enfortumab vedotin (MMAE)-resistant models.

Preclinical data presented at AACR 2025 highlighted IPH4502's superior efficacy. In urothelial cancer PDX models that developed resistance to enfortumab vedotin (PADCEV), IPH4502 maintained its activity and controlled tumor growth, whereas PADCEV lost efficacy. This underscores its differentiated profile and the opportunity to treat patients who no longer respond to existing Nectin-4 ADCs. Furthermore, IPH4502 demonstrated anti-tumor activity in PDX models with low or heterogeneous Nectin-4 expression from various tumor types, including triple-negative breast, esophageal, and head and neck cancers, where PADCEV showed limited or no efficacy. This broadens the potential reach of Nectin-4 targeting beyond urothelial cancer. The Phase I dose escalation study for IPH4502 is progressing well, with enrollment expected to complete before the end of Q1 2026, and preliminary safety and activity data anticipated in the first half of 2026. This program is purpose-built to overcome the limitations of existing Nectin-4 therapies, offering a potentially rapid path to late-stage development in areas of high unmet need.

ANKET Platform: Harnessing NK Cells for Cancer Therapy

Innate Pharma's proprietary ANKET (Antibody-based NK Cell Engager Therapeutics) platform is a first-in-class, multi-specific, plug-and-play technology designed to engage NK cells with tumor cells. It achieves this by triggering the NKp46 activating receptor, the most specific marker of human NK cells, which maintains stable expression on tumor-infiltrating NK cells.

IPH6501, Innate's lead proprietary second-generation ANKET, targets CD20 and incorporates an IL-2 variant to induce the expansion of patients' own NK cells. Preclinical data for IPH6501 demonstrated greater efficacy in depleting autologous CD20-positive B-cells compared to a T-cell engager, while inducing significantly less pro-inflammatory cytokines. This differentiated safety profile could be a key advantage in the crowded non-Hodgkin lymphoma space, particularly for frail, heavily pretreated patients, by limiting the risk of cytokine release syndrome. The Phase I study for IPH6501 in relapsed/refractory B-cell non-Hodgkin lymphoma is progressing, with initial safety, pharmacokinetic, and pharmacodynamic readouts, along with preliminary efficacy signals, expected by the end of 2025 and into 2026. The emerging safety profile could also position this asset in B-cell mediated autoimmune diseases.

Strategic Pillars and Pipeline Progress

Innate Pharma's sharpened focus is evident in the advancement of its three core clinical assets, each representing a distinct value proposition.

Lacutamab: A Promising Candidate in T-cell Lymphomas

Lacutamab, a first-in-class anti-KIR3DL2 antibody, is in development for cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), areas with significant unmet medical needs. The program has garnered substantial regulatory support, including FDA Breakthrough Therapy Designation for relapsed or refractory Sézary syndrome, FDA Fast Track, EMA PRIME designation, and Orphan Drug designation for CTCL.

Long-term follow-up data from the TELLOMAK Phase II trial showcased lacutamab's potential. In heavily pretreated Sézary syndrome patients (post-mogamulizumab), it achieved a global overall response rate of 42.9% and a median progression-free survival of 8.3 months, with a median duration of response of 25.6 months. For mycosis fungoides, the global overall response rate was 19.6%, with a median duration of response of 13.8 months and a median progression-free survival of 10.2 months, demonstrating consistent activity regardless of KIR3DL2 expression. The drug's excellent safety profile and positive impact on quality of life position it as a unique candidate for earlier systemic therapy in CTCL, potentially delaying disease progression. U.S. claims data suggests a larger market opportunity than previously estimated, with approximately 1,000 Sézary syndrome patients (300 new cases annually) and a broader CTCL population of 20,000 patients (5,000 new cases annually). Innate Pharma is nearing completion of the Phase III protocol for CTCL and aims to initiate the confirmatory trial next year, targeting potential accelerated approval in Sézary syndrome by 2027, contingent on securing financing. The company believes lacutamab has "significant potential in excess of 500 million" and can be a "profitable and value-creating opportunity."

Monalizumab: A Strategic Partnership with AstraZeneca

Monalizumab, a first-in-class anti-NKG2A checkpoint inhibitor, is a cornerstone of Innate Pharma's late-stage partnered assets with AstraZeneca. This collaboration is valued at up to $1.275 billion, with Innate having already received $450 million in upfront and milestone payments and eligible for up to an additional $825 million in development and commercial milestones. Innate will receive double-digit royalties on sales outside Europe and retains co-promotion rights with a 50% profit share in Europe, contributing to Phase III costs with a predefined cap.

The Phase III PACIFIC-9 trial, evaluating monalizumab in combination with durvalumab for unresectable Stage III non-small cell lung cancer, is fully recruited. Primary completion is anticipated in the first half of 2026, with data expected in the second half of 2026. This partnership provides a significant, de-risked value driver for Innate Pharma, leveraging AstraZeneca's global development and commercialization capabilities.

Other ANKET Programs

While the strategic focus has narrowed, Innate Pharma continues to evaluate other ANKET programs. The rights to IPH6101, a CD123-targeted ANKET, were returned from Sanofi as of July 1, 2025, and Innate is assessing its next steps, potentially exploring investigator-initiated research. Sanofi has pivoted the BCMA-targeted ANKET, IPH6401, to autoimmune indications, reflecting the ANKET platform's versatility beyond oncology. The B7H3-targeted ANKET, IPH6201, continues to progress in preclinical development with Sanofi.

Financial Performance and Liquidity

Innate Pharma's financial performance in the first half of 2025 reflects its strategic refocus. Total revenue for H1 2025 was €4.9 million, primarily from collaborations with AstraZeneca and Sanofi, and governmental research funding. Operating expenses reached €30.3 million, with R&D expenses decreasing by 29% year-over-year to €20.5 million, indicating a disciplined approach to resource allocation in line with program phasing. General and administrative expenses remained stable at €9.8 million.

For the full year 2024, the company reported €20.1 million in revenue, including €12.6 million from collaborations and €7.5 million from research tax credits. Operating expenses were €71.7 million, with R&D accounting for €52 million, a €4 million reduction from the prior year. This reduction was partly due to the maturity of clinical development programs.

As of June 30, 2025, Innate Pharma reported a cash position of €70.4 million in cash, cash equivalents, and financial assets. This provides a cash runway until the end of the third quarter of 2026, a projection that fully incorporates the impact of the company's recent restructuring plan. The €15 million strategic equity investment from Sanofi in April 2025 further strengthened the company's balance sheet. Innate Pharma is actively exploring financing options for lacutamab's confirmatory Phase III trial, considering both partnerships with improved deal terms and additional investor support, aiming to maximize value without undertaking a "bad deal."

Competitive Landscape and Positioning

Innate Pharma operates as a specialized biotechnology company within the highly competitive oncology market, positioning itself against larger, more diversified pharmaceutical giants such as AstraZeneca, Bristol-Myers Squibb (BMY), Merck (MRK), and Roche (RHHBY). While these larger players benefit from extensive resources, broad pipelines, and established commercial infrastructures, Innate Pharma carves out its niche through targeted innovation and differentiated technologies.

IPH4502 stands out against existing Nectin-4 ADCs like PADCEV (enfortumab vedotin). PADCEV's limitations, including toxicity-driven discontinuations, frequent relapses, and limited activity beyond urothelial cancer, create a significant unmet need that IPH4502 is designed to address. Its exatecan payload and unique binding epitope offer a differentiated resistance and toxicity profile, allowing it to target tumors resistant to MMAE-based ADCs and those with low or heterogeneous Nectin-4 expression, areas where PADCEV has shown limited efficacy. This technological advantage positions IPHA to potentially capture market share in post-PADCEV urothelial carcinoma and expand into new solid tumor indications.

Lacutamab's strong efficacy and excellent safety profile in CTCL, particularly in Sézary syndrome, differentiate it from other systemic therapies. In a disease with few tolerable options, especially for earlier stages, lacutamab's potential for durable responses and positive impact on quality of life could enable it to create a new market opportunity through early intervention.

The ANKET platform, exemplified by IPH6501, offers a unique mechanism of action compared to T-cell engagers in B-cell non-Hodgkin lymphoma. The stable expression of NKp46 on NK cells, coupled with IPH6501's ability to induce less pro-inflammatory cytokines, suggests a more benign safety profile that could be crucial for heavily pretreated and frail patients. Furthermore, the B7H3-targeted ANKET, IPH6201, provides an "alternative orthogonal mechanism" to the increasingly crowded B7H3 ADC landscape, offering a distinct therapeutic approach.

Innate Pharma's competitive advantages lie in its proprietary NK cell technology and strategic partnerships, which provide access to resources and distribution channels. However, its smaller scale and reliance on clinical-stage products present vulnerabilities, potentially leading to higher operational costs and pipeline risks compared to its larger rivals. The high barriers to entry in the biotech sector, including R&D costs and regulatory complexities, help protect Innate's specialized niche but also underscore the challenges of competing with well-capitalized industry leaders.

Conclusion

Innate Pharma S.A. is undergoing a transformative period, strategically focusing its resources on a select portfolio of high-value clinical assets. The company's differentiated technological platforms, particularly the IPH4502 ADC and the ANKET NK cell engagers, underpin its potential to address significant unmet medical needs in oncology. With lacutamab poised for a potential accelerated approval in Sézary syndrome and monalizumab advancing in a late-stage partnership with AstraZeneca, Innate Pharma possesses a compelling pipeline with multiple near-term catalysts.

The company's disciplined financial management, evidenced by its extended cash runway into Q3 2026, supports its focused strategic priorities. While challenges remain, particularly in securing financing for lacutamab's confirmatory Phase III trial, Innate Pharma's commitment to maximizing value through strategic partnerships or alternative investor support is clear. The investment thesis for Innate Pharma hinges on the successful clinical execution of its lead programs and its ability to leverage its technological differentiation to capture market share in specific, high-need indications, positioning it for long-term growth in the competitive oncology landscape.