Executive Summary / Key Takeaways

• Celcuity is a clinical-stage biotech focused on bringing its lead asset, gedatolisib, a differentiated pan-PI3K/mTOR inhibitor, to market for large unmet needs in solid tumors, particularly HR+/HER2- advanced breast cancer.
• Upcoming topline data readouts from the pivotal VIKTORIA-1 trial in second-line HR+/HER2- breast cancer (wild-type cohort Q3 2025, mutant cohort Q4 2025) represent the most significant near-term catalysts for the company.
• Gedatolisib's comprehensive PAM pathway inhibition and favorable safety profile observed in early trials, coupled with its IV administration advantages, position it as a potentially differentiated option against single-node inhibitors and other competitors.
• The company is strategically expanding gedatolisib's potential by initiating a Phase 3 trial (VIKTORIA-2) in the first-line endocrine-resistant breast cancer setting (first patient Q2 2025) and evaluating it in metastatic castration-resistant prostate cancer (preliminary Phase 1b data late Q2 2025).
• With approximately $205.7 million in cash and investments as of March 31, 2025, and access to additional debt tranches, Celcuity expects to fund its clinical development activities through 2026, though future financing may be required for commercialization.

Setting the Stage: Addressing Unmet Needs with Differentiated Technology

Celcuity Inc. is a clinical-stage biotechnology company strategically focused on developing targeted therapies for multiple solid tumor indications. Co-founded in 2012, the company initially explored a diagnostic platform before pivoting its primary focus to the clinical development of gedatolisib, a potent kinase inhibitor. This shift was solidified in April 2021 when Celcuity obtained exclusive global development and commercialization rights to gedatolisib from Pfizer Inc. (PFE), positioning it as the company's lead therapeutic candidate.

The core of Celcuity's approach lies in gedatolisib's unique mechanism of action. Unlike many currently approved or investigational therapies that target only a single node within the PI3K/AKT/mTOR (PAM) pathway, gedatolisib binds to all four Class I PI3K isoforms (p110α, p110β, p110γ, and p110δ) and both mTOR complexes (mTORC1 and mTORC2). This comprehensive inhibition of the PAM pathway is designed to overcome the limitations of single-node inhibitors, which can induce compensatory resistance through uninhibited subunits and feedback loops. Non-clinical studies highlight this differentiation, showing gedatolisib is equally potent and cytotoxic in breast and prostate cancer cell lines regardless of PIK3CA or PTEN mutational status, and at least 300 times more potent on average in breast cancer cells than single-node PAM inhibitors in these studies.

Beyond its molecular targeting, gedatolisib's intravenous (IV) route of administration on a three weeks-on, one week-off cycle offers potential advantages. This contrasts with continuous oral pan-PI3K or dual PI3K/mTOR inhibitors that faced development halts partly due to challenging toxicity profiles. In Celcuity's Phase 1b trial, gedatolisib demonstrated a favorable safety profile with manageable toxicity, including low rates of Grade 3 or 4 hyperglycemia (7%) and treatment discontinuation (<9%), notably lower than rates reported for the oral PI3Kα inhibitor alpelisib (39% Grade 3/4 hyperglycemia, 26% discontinuation) in its pivotal trial. The IV administration is also viewed favorably by oncologists and market access stakeholders, potentially allowing for better compliance monitoring and falling under the medical benefit category, which typically involves more streamlined reimbursement and potentially lower patient out-of-pocket costs compared to oral drugs under the pharmacy benefit. This aligns with the common practice in oncology where many widely prescribed drugs are administered in-office.

The competitive landscape for targeted oncology therapies, particularly in HR+/HER2- advanced breast cancer, is dynamic and includes established pharmaceutical giants like Novartis (NVS), Pfizer, and AstraZeneca (AZN), as well as smaller biotech firms like Exelixis (EXEL). These competitors offer various treatments, including other PI3K inhibitors, CDK4/6 inhibitors, and SERDs. Celcuity's differentiated pan-PAM inhibition and observed safety profile aim to carve out a distinct position. While larger competitors benefit from vast financial resources, established commercial infrastructure, and broader portfolios, Celcuity's strategic focus on identifying and targeting previously undetected drivers through its technology (though the CELsignia platform's role is less emphasized in recent disclosures compared to gedatolisib itself) and its potentially superior therapeutic profile represent its core competitive moat. The market for HR+/HER2- advanced breast cancer, especially in later lines and endocrine-resistant settings, presents a significant unmet need, indicated by the rapid adoption of recently approved therapies despite modest efficacy improvements. Oncologists are actively seeking new, more effective, and better-tolerated options.

Financial Performance Reflecting Development Investment

As a clinical-stage company, Celcuity has not generated revenue to date and continues to incur significant operating losses. For the three months ended March 31, 2025, the company reported a net loss of $37.0 million, a notable increase from the $21.6 million net loss for the same period in 2024. This widening loss is primarily driven by increased research and development (R&D) expenses, which rose by $11.6 million, or 56%, to $32.2 million in Q1 2025. This increase directly reflects the costs associated with advancing the pivotal VIKTORIA-1 trial, the ongoing CELC-G-201 trial, and the commencement of site activation activities for the VIKTORIA-2 trial, alongside higher employee and consulting costs. General and administrative (G&A) expenses also increased significantly by $2.1 million, or 112%, to $3.9 million in Q1 2025, attributed to growth in employee and consulting expenses, professional fees, and expanding infrastructure necessary to support the company's clinical programs and public company requirements. Interest expense also rose due to the incremental funding from the AR Loan Agreement in May 2024.

Celcuity's operations are heavily reliant on external financing. As of March 31, 2025, the company held approximately $205.7 million in cash, cash equivalents, and short-term investments. This liquidity position was bolstered by several financing activities, including approximately $5.6 million from warrant exercises in March 2025 and significant proceeds from an equity offering ($56.3 million net) and the initial funding of a debt facility ($61.7 million net from the AR Loan Agreement) in May 2024.

The AR Loan Agreement provides access to up to $180.0 million in total, with potential additional tranches contingent on achieving clinical milestones and meeting financial covenants. A recent amendment in May 2025 extended the draw period for the Term D tranche to August 31, 2025, and adjusted liquidity covenants, highlighting the ongoing need to manage financial flexibility as trials progress.

The company also retains access to up to $125.0 million under an Open Market Sale Agreement with Jefferies (JEF). Based on its current business plan, Celcuity anticipates that its existing cash, investments, and available debt tranches will provide sufficient capital to fund its clinical development program activities through 2026. However, the company acknowledges that substantial additional financing will be required to support potential commercialization efforts and future growth initiatives.

Strategic Catalysts and Future Outlook

Celcuity's immediate future is defined by critical clinical milestones that could fundamentally alter its trajectory. The most anticipated events are the topline data readouts from the Phase 3 VIKTORIA-1 trial in HR+/HER2- advanced breast cancer patients who have received prior CDK4/6 therapy. The company expects to report data from the PIK3CA wild-type cohort in the third quarter of 2025, followed by data from the PIK3CA mutant cohort in the fourth quarter of 2025. Positive results from the wild-type cohort are expected to support the filing of the company's first new drug application (NDA), potentially paving the way for a transition to a commercial-stage company. Management estimates the peak revenue potential for this second-line indication could exceed $2.0 billion with just 40% market penetration, reflecting the significant size of the eligible patient population (estimated 30,000-35,000 in the US).

Expanding its strategic reach, Celcuity is also advancing gedatolisib into earlier lines of therapy and new tumor types. Site activation is underway for the Phase 3 VIKTORIA-2 trial, evaluating gedatolisib as a first-line treatment for HR+/HER2- advanced breast cancer patients who are resistant to endocrine therapy. The first patient in this trial is expected to be dosed in the second quarter of 2025. This population represents a distinct and large unmet need, with an estimated 15,000 to 20,000 patients diagnosed annually in the US alone. Management projects that approval in this indication could add up to $3 billion to the addressable US market potential for gedatolisib, justifying the strategic decision, enabled by recent financing, to accelerate this trial's initiation.

In parallel, the company is exploring gedatolisib's potential in metastatic castration-resistant prostate cancer (mCRPC) through the Phase 1b/2 CELC-G-201 trial. Enrollment in the Phase 1b dose escalation portion is complete, and preliminary topline data is anticipated in late second quarter 2025. This early-stage data will focus on dose optimization and initial efficacy signals (e.g., 6-month radiographic PFS) to guide further development in this indication, which shares biological similarities with ER-positive breast cancer regarding the PAM pathway's role. An investigator-sponsored trial in endometrial cancer also leverages prior encouraging data, further broadening the potential applications of gedatolisib.

The outlook for Celcuity involves continued high R&D spending to support these trials, with G&A expenses also expected to rise as the company prepares for potential commercialization. The success of the upcoming data readouts is paramount, not only for regulatory progress but also for the company's ability to secure future financing on favorable terms and realize the substantial market opportunities it is pursuing.

Risks and Competitive Dynamics

Despite the promising pipeline and upcoming catalysts, Celcuity faces significant risks inherent to the clinical-stage biotechnology sector. The success of gedatolisib hinges entirely on positive data from the ongoing Phase 3 trials and subsequent regulatory approvals, which are never guaranteed. Clinical trial outcomes can be unpredictable, and delays or failures could severely impact the company's prospects. Reliance on third parties for conducting trials and manufacturing introduces operational risks. The competitive landscape is intense, with larger, well-funded companies developing competing therapies. While gedatolisib's differentiated mechanism and safety profile offer potential advantages, market adoption upon approval will depend on demonstrating a clinically meaningful benefit (KOLs suggest a 3-month incremental PFS improvement is meaningful) and effectively competing against established and emerging treatments.

Financial risk is also material, as the company is not yet profitable and requires substantial capital to fund its operations through clinical development and potential commercial launch. Although current funding is expected to last through 2026, the need for future financing could lead to dilution for existing stockholders or restrictive covenants under new debt agreements.

External factors such as disruptions at regulatory agencies like the FDA or changes in trade policies could also impact timelines and costs. The ability to accurately estimate and manage clinical trial costs, which are a significant expense, is crucial. Ultimately, the realization of the estimated multi-billion dollar market potential for gedatolisib depends on successful clinical development, regulatory approval, effective commercial execution, and favorable market dynamics in a competitive environment.

Conclusion

Celcuity stands at a pivotal juncture, with its lead therapeutic candidate, gedatolisib, poised to deliver key clinical data that could validate its potential as a differentiated treatment for large oncology populations. The company's strategy to target the PAM pathway comprehensively across multiple indications, particularly in HR+/HER2- advanced breast cancer and mCRPC, leverages gedatolisib's unique mechanism and observed favorable safety profile. Upcoming topline results from the VIKTORIA-1 trial in Q3 and Q4 2025 represent the most critical near-term catalysts, with the potential to support the company's first NDA filing and initiate a transformation towards commercialization.

While significant financial resources are required to fund ongoing and planned clinical trials, the company's recent financing activities have extended its runway through 2026, enabling strategic expansions like the accelerated initiation of the VIKTORIA-2 trial in the first-line setting. The competitive landscape is challenging, but Celcuity's focus on a differentiated mechanism and potential tolerability advantages, coupled with the strategic benefits of IV administration, positions it to potentially capture significant market share if clinical success is achieved. Investors will be closely watching the upcoming data readouts as the primary indicators of Celcuity's ability to translate its promising pipeline into tangible value and address the substantial unmet needs in its target markets.