Annual Report for Fiscal Year Ending December 31, 2025 (Form 10-K)

Management's Discussion and Analysis of Financial Condition and Results of Operations

You should read the following discussion and analysis of our financial condition and results of operations together in conjunction with our financial statements and the related notes included elsewhere in this Annual Report. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report, including information with respect to our plans and strategy for our business and expected financial results, includes forward-looking statements that involve risks and uncertainties. You should review the "Risk Factors" discussed in Item 1A of Part I of this Annual Report.

Overview

Celcuity is a clinical-stage biotechnology company focused on the development of targeted therapies for the treatment of multiple solid tumor indications. The Company's lead therapeutic candidate is gedatolisib, a kinase inhibitor of the phosphatidylinositol 3-kinase ("PI3K"), serine/threonine-protein kinase protein kinase B ("AKT"), mechanistic target of rapamycin ("mTOR") pathway that binds to all class I PI3K isoforms and the mTOR complexes, mTORC1 and mTORC2. By targeting all class I PI3K isoforms and mTORC1/2, gedatolisib induces comprehensive inhibition of the PI3K/AKT/mTOR ("PAM") pathway. Its mechanism of action and pharmacokinetic properties are differentiated from other currently approved and investigational therapies that target PI3Kα, AKT, or mTORC1 alone or together. Our Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant with or without palbociclib in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ("HR+/HER2-") advanced breast cancer ("ABC") has completed enrollment and reported detailed results for cohort 1, patients with PIK3CA wild-type ("WT") tumors, and has completed enrollment of cohort 2, patients with PIK3CA mutant-type ("MT") tumors. Our Phase 3 clinical trial, VIKTORIA-2, evaluating gedatolisib in combination with a cyclin-dependent kinase ("CDK") 4/6 inhibitor and fulvestrant as first-line treatment for patients with endocrine treatment resistant HR+/HER2- ABC is ongoing. A Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer ("mCRPC"), is ongoing.

In April 2021, we obtained exclusive global development and commercialization rights to gedatolisib under a license agreement with Pfizer. We believe gedatolisib's unique mechanism of action, differentiated chemical structure, favorable pharmacokinetic properties, and intravenous route of administration offer distinct advantages over currently approved and investigational therapies that target PI3Kα, AKT, or mTORC1 alone or together.

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Overcomes limitations of therapies that only inhibit a single class I PI3K isoform, AKT, or one mTOR kinase complex.

Gedatolisib is a pan-class I isoform PI3K inhibitor with low nanomolar potency for the p110α, p110β, p110γ, and p110δ isoforms and the mTORC1 and mTORC2 complexes. By targeting all class I PI3K isoforms and mTORC1/2, gedatolisib induces comprehensive inhibition of the PAM pathway. Each PI3K isoform and mTOR complex is known to preferentially affect different signal transduction events that involve tumor cell survival, depending upon the aberrations associated with the linked pathway. When a therapy only inhibits a single class I PI3K isoform (e.g., alpelisib, a PI3Kα inhibitor), AKT (e.g., capivasertib, an AKT inhibitor) or only one mTOR kinase complex (e.g., everolimus, an mTORC1 inhibitor), numerous feedforward and feedback loops between the PI3K isoforms and mTOR complexes cross-activate the uninhibited sub-units. This, in turn, induces compensatory resistance that reduces the efficacy of isoform specific PI3Kα, AKT, or mTORC1 kinase inhibitors. Inhibiting all four PI3K isoforms and both mTOR complexes, as gedatolisib does, thus prevents the confounding effect of isoform interaction that may occur with isoform-specific PI3K inhibitors and the confounding interaction between PI3K isoforms, AKT, and mTOR.

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Better tolerated by patients than oral PI3K and mTOR drugs.

Gedatolisib is administered intravenously on a four-week cycle of three weeks-on, one week-off, in contrast to the orally administered pan-PI3K or dual PI3K/mTOR inhibitors that are no longer being clinically developed. Oral pan-PI3K or PI3K/mTOR inhibitors have repeatably been found to induce significant side effects that were not well tolerated by patients. This typically leads to a high proportion of patients requiring dose reductions or treatment discontinuation. The challenging toxicity profile of these drug candidates ultimately played a significant role in the decisions to halt their development, despite showing promising efficacy. By contrast, gedatolisib's comprehensive inhibition of the PAM pathway at low nanomolar potency, IV route of administration, and pharmacokinetic properties enables it to achieve optimal anti-proliferative effects on tumor cells without inducing the levels of hyperglycemia, rash, and diarrhea typically associated with oral single-component inhibitors of the PAM pathway.

Isoform-specific PI3K or mTORC1 inhibitors administered orally were developed to reduce toxicities in patients. While the range of toxicities associated with single-component PAM inhibitors is narrower than oral pan-PI3K or PI3K/mTOR inhibitors, administering them orally on a continuous basis can still lead to challenging toxicities. The experience with an FDA-approved oral p110-α specific inhibitor, PIQRAY, illustrates the challenge. In its Phase 3 pivotal trial, PIQRAY was found to induce a Grade 3 or 4 adverse event ("AE") related to hyperglycemia in 39% of patients evaluated. In addition, 26% of patients discontinued alpelisib due to treatment related AEs. By contrast, in the 103-patient dose expansion portion of the Phase 1b clinical trial with gedatolisib, only 7% of patients experienced Grade 3 or 4 hyperglycemia and less than 9% discontinued treatment.

As of December 31, 2025, 1,127 patients and healthy volunteers have received gedatolisib in 12 completed or ongoing clinical trials. Of these, 123 patients with solid tumors were treated with gedatolisib as a single agent in two clinical trials, 36 healthy volunteers were treated in two clinical trials, and the remaining 968 patients received gedatolisib in combination with other anti-cancer agents in eight clinical trials. Additional patients received gedatolisib in combination with other anti-cancer agents in 10 investigator sponsored clinical trials.

B2151009 Phase 1b Trial

A Phase 1b dose-finding trial with an expansion portion for safety and efficacy evaluated gedatolisib when added to either the standard doses of palbociclib plus letrozole or palbociclib plus fulvestrant in patients with HR+/HER2- ABC. PI3K mutation status was not used as an eligibility criterion. Patient enrollment for the trial is complete.

A total of 138 patients with HR+/HER2- ABC were dosed in the clinical trial. Four patients from this study continue to receive study treatment, as of December 31, 2025, each of whom has received study treatment for more than six years.

	●	35 patients were enrolled in two dose escalation arms to evaluate the safety and tolerability and determine the maximum tolerable dose ("MTD") of gedatolisib when used in combination with the standard doses of palbociclib and endocrine therapies. The MTD was determined to be 180 mg administered intravenously once weekly.
	●	103 patients were enrolled in one of four expansion arms (A, B, C, D) to determine if the triplet combination of gedatolisib plus palbociclib and letrozole or gedatolisib plus palbociclib and fulvestrant produced a superior objective response (OR), compared to historical control data of the doublet combination (palbociclib plus endocrine therapy). All patients received gedatolisib in combination with standard doses of palbociclib and endocrine therapy (either letrozole or fulvestrant). In Arms A, B, and C, patients received an intravenous dose of 180 mg of gedatolisib once weekly. In Arm D, patients received an intravenous dose of 180 mg of gedatolisib on a four-week cycle of three-weeks-on, one-week-off. Objective response was determined using Response Evaluation Criteria in Solid Tumors v1.0, or RECIST v1.0.

	○	Arm A: ABC with progression and no prior endocrine-based systemic therapy or a CDK4/6 inhibitor in the metastatic setting. First-line endocrine-based therapy for advanced disease (CDK4/6 treatment naive).
	○	Arm B: ABC with progression during one or two prior endocrine-based systemic therapies in the advanced setting, with no prior therapy with any CDK inhibitor. Second- or third-line endocrine-based therapy for metastatic disease.
	○	Arm C: ABC with progression during one or two prior endocrine-based systemic therapies in the advanced setting and following prior therapy with a CDK inhibitor. Second- or third-line endocrine-based therapy for advanced disease.

○

Arm D: ABC with progression during one or two prior endocrine-based systemic therapies in the advanced setting and following prior therapy with a CDK inhibitor. Second- or third-line endocrine-based therapy for advanced disease.

	●	For the 103 patients enrolled in the expansion portion of the Phase 1b clinical trial, the ORR in aggregate among patients with evaluable tumors was 63%.
	●	Best responses, as measured by RECIST v1.0, are shown in the following chart for Arm A (1st line patients) and Arm D (2nd/3rd line patients who received the VIKTORIA-1 Phase 3 trial dosing regimen). The dotted line represents the cutoff for partial response (PR), defined as a 30% reduction from the baseline tumor assessment.

Source: Layman SABCS 2021

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Safety analysis:

	○	For all arms in aggregate, all patients experienced at least one Grade 1 or Grade 2 treatment-emergent adverse event. The Grade 3 and 4 treatment-emergent adverse events occurring in at least 20% of patients were neutropenia (63%), stomatitis (27%) and rash (20%). Neutropenia is a known class effect of CDK4/6 inhibitors. Stomatitis was reversible in most patients with a steroidal mouth rinse. All grades of treatment-related adverse events related to hyperglycemia were reported in 22% of patients; Grade 3 or 4 hyperglycemia was reported in 7% of patients. Gedatolisib was discontinued in less than 9% of patients.
	○	For the patients in Arm D, who received the Phase 3 dosing schedule, Grade 3 and 4 treatment-emergent adverse events occurring in at least 20% of patients were neutropenia (67%), leukopenia (22%), and stomatitis (22%). All grades of treatment-related adverse events related to hyperglycemia were reported in 26% of patients; Grade 3 or 4 hyperglycemia were reported in 7% of patients. Gedatolisib was discontinued in 4% of patients.

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Best overall response data for each arm is presented in the table below:

Total Expansion Arms (N=103)
		Arm A		Arm B		Arm C		Arm D
Prior Therapy		1L CDKi-naive		2L+ CDKi-naive		2L/3L CDKi-pretreated		2L/3L CDKi-pretreated
n (Full, response evaluable)		31, 27		13,13		32, 28		27, 27
Study Treatment		P + L + G		P + F + G		P + F + G		P + F + G
Gedatolisib schedule		weekly		weekly		weekly		3 wks on/1 wk off
ORR (1) (evaluable)		85%		77%		36%		63%
mPFS (2), mos (range)		48.4 (16.9, NR)		12.9 (7.6, 38.3)		5.1 (3.3, 7.5)		12.9 (7.4, 16.7)
PFS % at 12 mos (2)		72.1%		54.5%		23.6%		53.2%

		WT				MT				WT				MT				WT				MT				WT				MT
PIK3CA status			81	%			16	%			69	%			31	%			75	%			25	%			56	%			41	%
ORR (evaluable)			81	%			100	%			78	%			75	%			25	%			63	%			60	%			73	%
PFS at 12 months			74	%			60	%			50	%			67	%			22	%			29	%			49	%			60	%

(1) ORR represents PR, except in Arm A, which had 1 CR = Complete response. Responses per RECIST 1.1; (2) Includes 2 unconfirmed PR

Abbreviations: 1L = first line; 2L = second line; mos = months; NR = not reached; ORR = objective response rate; PFS = progression free survival

Source: Layman R. et. al, Lancet Oncol., 2024

Additional results from the Phase 1b portion of the clinical trial were presented at the ESMO congress in October 2025. The analyses reported efficacy data from patients who were treated with the same drug regimen being evaluated in the VIKTORIA-1 study, gedatolisib combined with fulvestrant and palbociclib. This included patients from Escalation Arm B and Expansion Arms B, C and D of the Phase 1b study.

As described above, patients in Escalation Arm B and Expansion Arms B and C received a 180 mg dose of gedatolisib once weekly ("weekly dose"). Patients in Expansion Arm D received a 180 mg dose of gedatolisib on days 1, 8, and 15 of a four-week cycle ("intermittent dose"), which is the same dose regimen patients in the VIKTORIA-1 study receive. The proportion of patients who received the intermittent dose of gedatolisib was 37% for those with PIK3CA MT tumors and 25% for those with PIK3CA WT tumors. The proportion of patients who received prior treatment with a CDK4/6 inhibitor was 73% for those with PIK3CA WT tumors, and 71% for those with PIK3CA MT tumors.

Median PFS and the ORR were assessed in sub-groups of patients according to their PIK3CA status (Table 1). For all analyzed patients with PIK3CA MT tumors (n=30), median PFS was 14.6 months and the ORR in response evaluable patients was 48%. Median PFS was 19.7 months and the ORR was 64% in patients with PIK3CA MT tumors who received the intermittent dose of gedatolisib used in the VIKTORIA-1 study. For patients with PIK3CA WT tumors (n=60), median PFS was 9.0 months and the ORR in response evaluable patients was 41%. Median PFS was 9.1 months and the ORR was 53% in patients with PIK3CA WT tumors who received the intermittent dose of gedatolisib used in the VIKTORIA-1 study.

Table 1: Efficacy Analysis of Phase 1b Patients Treated with Gedatolisib Plus Palbociclib Plus Fulvestrant

		PIK3CA MT								PIK3CA WT
		All				Intermittent Dose				All				Intermittent dose
N			30				11				60				15
Median PFS (months)			14.6				19.7				9.0				9.1
ORR			48	%			64	%			41	%			53	%

VIKTORIA-1 Phase 3 Trial

We have completed enrollment of our Phase 3, open-label, randomized clinical trial, VIKTORIA-1, to evaluate the efficacy and safety of gedatolisib treatment regimens in adults with HR+/HER2- ABC whose disease has progressed after prior CDK4/6 therapy in combination with an aromatase inhibitor. Over 200 clinical sites in North America, Europe, Latin America, and Asia-Pacific are participating in the study. The first patient was dosed in this trial in December 2022.

The VIKTORA-1 Phase 3 clinical trial involves two study cohorts that enable separate evaluation of subjects according to their PIK3CA status. Subjects who met eligibility criteria and had PIK3CA WT tumors (cohort 1) were randomly assigned (1:1:1) to receive a regimen of either gedatolisib, palbociclib, and fulvestrant (Arm A), gedatolisib and fulvestrant (Arm B), or fulvestrant (Arm C). During the fourth quarter of 2024, we achieved our enrollment goal of 351 subjects for the PIK3CA WT cohort. The primary completion date for this cohort was achieved in May 2025 and the database cut-off date for this cohort was May 30, 2025. Subjects who met eligibility criteria and had PIK3CA MT tumors (cohort 2) were randomly assigned (3:3:1) to receive a regimen of either gedatolisib, palbociclib, and fulvestrant (Arm D), alpelisib and fulvestrant (Arm E), or gedatolisib and fulvestrant (Arm F). Enrollment of approximately 350 subjects who have PIK3CA MT tumors is complete. We expect topline data for cohort 2 to be available in the second quarter of 2026.

On July 28, 2025, we announced topline data from the PIK3CA WT cohort of the VIKTORIA-1 clinical trial and on October 18, 2025, at the ESMO congress, additional efficacy and safety results from this cohort were presented. The key efficacy and safety data from the PIK3CA WT cohort showed:

	●	The gedatolisib triplet (gedatolisib, fulvestrant and palbociclib) demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 76% compared to fulvestrant (based on a hazard ratio [HR] of 0.24, 95% confidence interval [CI] 0.17-0.35; p<0.0001). The median PFS, as assessed by blinded independent central review ("BICR"), was 9.3 months with the gedatolisib triplet versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months.
	●	The gedatolisib doublet (gedatolisib and fulvestrant) also demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 67% compared to fulvestrant (HR of 0.33, 95% CI 0.24-0.48; p<0.0001). The median PFS, as assessed by BICR, was 7.4 months with the gedatolisib doublet versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months.
	●	The ORR of the gedatolisib triplet was 31% compared to 1% with fulvestrant and the median DOR was 17.5 months. The ORR of the gedatolisib doublet was 28.3% and the median DOR was 12.0 months. The median DOR was not determinable for fulvestrant because there was only one objective response.
	●	The gedatolisib triplet and doublet were generally well tolerated in the trial with mostly low-grade TRAEs. The most common Grade 3 TRAEs for the gedatolisib triplet, gedatolisib doublet, and fulvestrant groups included neutropenia (52.3%, 0%, and 0.8% of patients, respectively); stomatitis (19.2%, 12.3%, and 0% of patients, respectively) rash (4.6%, 5.4%, and 0% of patients, respectively); and hyperglycemia (2.3%, 2.3%, and 0% of patients, respectively). The primary Grade 4 TRAEs for the gedatolisib triplet and gedatolisib doublet groups were neutropenia (10.0% and 0.8%, respectively), leukopenia (0.8% in the gedatolisib triplet group) and pneumonitis (0.8% in gedatolisib doublet group). TRAEs led to the discontinuation of study treatment in 2.3% of patients in the gedatolisib triplet group, 3.1% in the gedatolisib doublet group, and 0% in the fulvestrant group.

The detailed results from cohort 1, PIK3CA WT cohort, established several new milestones in the history of drug development for HR+/HER2- ABC:

	●	The hazard ratios for the gedatolisib triplet and doublet are more favorable than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC.
	●	The 7.3- and 5.4-months incremental improvements in median PFS for the gedatolisib triplet and gedatolisib doublet over fulvestrant, respectively, are higher than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC receiving at least their second line of therapy.
	●	Gedatolisib is the first inhibitor targeting the PAM pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA WT ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.
	●	The median DOR and incremental ORR improvement relative to control for the gedatolisib triplet and doublet are the highest reported for an endocrine therapy-based regimen in 2L HR+/HER2- ABC.

The median PFS benefit of the gedatolisib triplet and doublet compared to fulvestrant was consistent across subgroups with the gedatolisib triplet showing higher clinical benefit in nearly all subgroups compared to the gedatolisib doublet, particularly for patients who were pre/perimenopausal, endocrine therapy resistant, or had visceral metastases. For patients enrolled in the United States and Canada, median PFS was 19.3 months (HR=0.13; 90% CI: 0.07-0.29) for the gedatolisib triplet and 14.9 months (HR=0.35; 90% CI: 0.17-0.76) for the gedatolisib doublet.

In December 2025, updated efficacy and safety results from the Phase 3 VIKTORIA-1 PIK3CA WT cohort were presented at the 2025 San Antonio Breast Cancer Symposium including patient sub-group analyses, safety analyses and patient reported outcomes for well-being measures.

●	For patients enrolled in the U.S., Canada, Western Europe, and Asia Pacific, median PFS was 16.6 months with the gedatolisib triplet and 7.1 months with the gedatolisib doublet versus 1.9 months for fulvestrant (HR=0.14; 95% CI: 0.08-0.28; p<0.0001).
●	Both gedatolisib regimens delayed time to definitive deterioration versus fulvestrant according to patient reported outcomes for well-being measures that included mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (the EQ-5D-5L score). The median time to definitive deterioration was 23.7 months (HR=0.39; 95% CI: 0.25-0.67; p = 0.0003) for patients treated with the gedatolisib triplet and not reached for the gedatolisib doublet (HR=0.37; 95% CI: 0.24-0.66; p = 0.0003) versus 4.0 months for fulvestrant. Additionally, for the first eight cycles of treatment, the patients' assessment of their well-being remained stable relative to their assessment prior to starting treatment with gedatolisib.

With these results, the gedatolisib regimens represent a new potential standard of care for patients with HR+/HER2-, PIK3CA WT ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.

Results from cohort 2 of the VIKTORIA-1 Phase 3 clinical trial, the PIK3CA MT cohort, are expected to be available in the second quarter of 2026.

VIKTORIA-2 Phase 3 Trial

In July 2025, we dosed the first patient in VIKTORIA-2, a Phase 3, multi-center, open-label, randomized, clinical trial designed to evaluate the efficacy and safety of gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- endocrine treatment resistant ABC. For the CDK4/6 inhibitor, investigators may choose either ribociclib or palbociclib. This multi-center, international trial enrolled 35evaluable subjects in the safety run-in portion of the study to evaluate the safety of gedatolisib when combined with ribociclib and fulvestrant. The safety run-in was completed in the first quarter of 2026. In the Phase 3 portion of the study, approximately 638 subjects are expected to be randomized and assigned to Cohort 1 (PIK3CA WT) or Cohort 2 (PIK3CA MT) based on their PIK3CA status. Subjects in each cohort are expected to be randomized on a 1:1 basis to either Arm A (gedatolisib with fulvestrant and ribociclib or palbociclib) or Arm B (fulvestrant and ribociclib or palbociclib). We intend to provide an update on our final Phase 3 study design in the second quarter of 2026. It is expected that approximately 200 clinical sites across North America, Europe, and Asia-Pacific will participate, including many sites included in the VIKTORIA-1 clinical trial.

CELC-G-201 Phase 1b/2 Trial

We received approval from the FDA in mid-2023 to proceed with the clinical development of gedatolisib in combination with Nubeqa^® (darolutamide), an approved androgen receptor inhibitor, for the treatment of patients with mCRPC. We have since initiated a Phase 1b/2 clinical trial, CELC-G-201, that will enroll up to 54 participants with mCRPC who progressed after treatment with an androgen receptor inhibitor. The first patient was dosed in this trial in February 2024.

The primary objectives of the Phase 1b portion of the trial include assessment of the safety and tolerability of gedatolisib in combination with darolutamide and determination of the recommended Phase 2 dose ("RP2D") of gedatolisib. The primary objective of the Phase 2 portion of the trial is to assess the radiographic PFS at six months of patients who received the RP2D.

In the Phase 1b portion of the clinical trial, 38 patients with mCRPC were randomly assigned to receive 600 mg of darolutamide twice daily combined with either 120 mg of gedatolisib in Arm 1 or 180 mg of gedatolisib in Arm 2. In both arms, gedatolisib was administered once weekly for three weeks, then one week off. Additionally, all patients received prophylactic treatment for stomatitis.

On June 30, 2025, we announced preliminary data for the CELC-G-201 Phase 1b trial, utilizing a May 30, 2025 data cut-off. Based on these data, we amended the clinical trial protocol to enable exploration of additional doses in the Phase 1b portion of this clinical trial to determine the RP2D. Once RP2D is determined, an additional 12 participants will then be enrolled in the Phase 2 portion of the study at the RP2D level to enable evaluation of 30 participants treated with the RP2D of gedatolisib.

On October 18, 2025, at the ESMO congress, we presented updated clinical results for the CELC-G-201 Phase 1b trial based on an August 15, 2025 data cut-off. Among the 38 patients enrolled, 61% had received one line of prior systemic therapy and 39% had received at least two or more lines of prior therapy. Median duration of follow-up was 9.0 months.

The six-month radiographic progression-free survival ("rPFS") rate and median rPFS for patients from both arms combined was 67 % and 9.1 months, respectively. For patients treated with 120 mg gedatolisib, the six-month rPFS rate was 74% and median rPFS was 9.5 months. For patients treated with 180 mg gedatolisib, the six-month rPFS rate was 61% and the median rPFS was 7.4 months.

The combination of gedatolisib and darolutamide was generally well tolerated in the trial with mostly low-grade TRAEs. No dose limiting toxicities were observed in either arm. The only Grade 3 TRAEs for patients from both arms combined included rash (5.3%), stomatitis (2.6%), and pruritus (2.6%); no Grade 3 hyperglycemia was reported. Additionally, no Grade 4 or 5 TRAEs were observed, and no patients discontinued study treatment due to a TRAE.

In the amended Phase 1/1b portion of the clinical trial, up to six patients are planned to be enrolled in each of three arms and treated with different doses. Upon completion of Phase 1, up to an additional 40 patients will be randomly assigned to up to four Phase 1b cohorts to determine the RP2D. Dose levels will be selected based on the results from the Phase 1 clinical trial. In the Phase 2 dose expansion study, which will include subjects from the Phase 1/1b clinical trial, up to 18 additional subjects will be enrolled to achieve a total of approximately 30 subjects treated with the RP2D. All patients will also receive standard doses of darolutamide.

Investigator-Sponsored Trials

In an investigator-sponsored Phase 2 clinical trial, 44 patients with HER2+/PIK3CA mutated metastatic breast cancer were treated with gedatolisib plus standard doses of trastuzumab-pkrb. No prophylaxis for stomatitis was administered. The median number of prior anti-HER2 therapies enrolled patients received in the metastatic setting was four or more; 86% of patients had received at least three prior anti-HER2 therapies. The data cut-off was February 10, 2025.

Key efficacy and safety results, as presented at the American Society of Clinical Oncology meeting in June 2025, showed:

	●	The ORR among all patients enrolled was 43%.
	●	Median PFS was 6.0 months (95% CI, 5.0-7.7).
	●	Median overall survival was 24.7 months (95% CI; 17.3-NA).
	●	No patients discontinued gedatolisib due to a treatment-related AE.
	●	One (2.3%) patient experienced Grade 3 hyperglycemia.

An investigator sponsored trial has been initiated in collaboration with the Dana-Farber Cancer Institute and Massachusetts General Hospital to evaluate gedatolisib in combination with abemaciclib and letrozole in patients with endometrial cancer.

Recent Developments

	●	In January 2026, the FDA accepted for filing our NDA for gedatolisib in HR+/HER2- PIK3CA WT ABC. The FDA granted Priority Review and assigned a PDUFA goal date of July 17, 2026.
	●	In March 2026, efficacy and safety results from the PIK3CA WT cohort of the Phase 3 VIKTORIA-1 clinical trial of gedatolisib were published in the Journal of Clinical Oncology. The cohort consisted of patients with HR+/HER2-/PIK3CA WT ABC whose disease progressed while on or after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

Results of Operations

We have not generated any revenue from product sales or other sources to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not and have never been profitable and have incurred losses in each period since our inception in 2012. For the years ended December 31, 2025 and 2024, we reported a net loss of $177.0 million and $111.8 million, respectively. As of December 31, 2025, we had an accumulated deficit of $448.9 million. As of December 31, 2025, we had $441.5 million in cash, cash equivalents and short-term investments.

Components of Operating Results

Revenue

To date, we have not generated any revenue. Upon the execution of the Pfizer license agreement in April 2021, we acquired exclusive world-wide licensing rights to develop and commercialize gedatolisib. In 2022, we initiated VIKTORIA-1, a Phase 3 clinical trial, to support potential regulatory approval to market gedatolisib. Our Phase 3 clinical trial, VIKTORIA-2, and Phase 1b/2 clinical trial, CELC-G-201, are ongoing.

Pursuant to the FDA's RTOR program, in September 2025 we made the first pre-submission of our NDA to the FDA and completed the final NDA submission to the FDA on November 17, 2025. The FDA formally accepted our NDA submission on January 16, 2026, designated it for Priority Review, and has assigned a PDUFA target goal date of July 17, 2026. If we obtain regulatory approvals to market gedatolisib, we expect to generate revenue from sales of the drug commencing in the second half of 2026.

Research and Development

Since our inception, we have primarily focused on research and development of gedatolisib, a PI3K/mTOR targeted therapy. Research and development expenses primarily include:

	●	employee-related expenses related to our research and development activities, including salaries, benefits, recruiting, travel and stock-based compensation expenses;
	●	laboratory supplies;
	●	consulting fees paid to third parties;
	●	clinical trial costs;
	●	validation costs for gedatolisib; and
	●	facilities expenses.

General and Administrative

General and administrative expenses consist primarily of salaries, benefits and stock-based compensation related to our executive, finance and support functions. Other general and administrative expenses include professional fees for auditing, tax, and legal services associated with being a public company, director and officer insurance, software costs, investor relations and travel expenses for our general and administrative personnel.

Sales and Marketing

Expenses and costs related to marketing, supply chain, distribution, market access and other commercial operations related activities are being incurred in anticipation of the commercialization of gedatolisib. These expenses consist primarily of employee-related expenses, professional and consulting fees related to these functions and operations, software costs, and the acquisition of data required to support our market analysis for gedatolisib. We expect sales and marketing expenses to increase as we get closer to a potential FDA approval date.

Interest Expense

Interest expense to date is primarily related to the A&R Loan Agreement and the Notes (each as defined below).

Interest Income

Interest income consists of interest income earned on our cash, cash equivalents, and investment balances.

Results of Operations

Comparison of the Years Ended December 31, 2025 and 2024

The following table summarizes our results of operations (in thousands):

		Year Ended
		December 31,								Increase (Decrease)
		2025				2024				$				%
Statements of operations data:
Operating expenses:
Research and development		$	144,995			$	104,203			$	40,792				39	%
General and administrative			27,197				9,064				18,133				200
Total operating expenses			172,192				113,267				58,925				52
Loss from operations			(172,192	)			(113,267	)			(58,925	)			52
Other (expense) income:
Interest expense			(17,148	)			(10,280	)			(6,868	)			67
Interest income			12,298				11,768				530				5
Other (expense) income, net			(4,850	)			1,488				(6,338	)			(426	)
Net loss before income taxes			(177,042	)			(111,779	)			(65,263	)			58
Income taxes			-				-				-				-
Net loss		$	(177,042	)		$	(111,779	)		$	(65,263	)			58	%

Research and Development

During the year ended December 31, 2025, our research and development expenses were $145.0 million, representing an increase of $40.8 million, or 39%, compared to 2024. The increase was primarily due to a $26.7 million increase in employee-related and consulting expenses, of which $13.1 million related to commercial headcount additions and other launch activities. The remaining increase was primarily due to a $6.0 million increase in activities supporting our ongoing clinical trials, a $5.0 million development milestone payment under the license agreement with Pfizer, and a $3.1 million increase in other costs primarily related to commercial launch activities.

Conducting research and development is central to our business model. We plan to continue to increase our research and development expenses for the foreseeable future as we seek to continue to develop gedatolisib, including conducting the VIKTORIA-1 and VIKTORIA-2 Phase 3 clinical trials, and the CELC-G-201 Phase 1b/2 clinical trial.

General and Administrative

During the year ended December 31, 2025, our general and administrative expenses were $27.2 million, representing an increase of $18.1 million, or 200%, compared to 2024. The increase was primarily due to a $14.9 million increase in employee-related and consulting expenses, of which $10.4 million related to non-cash stock-based compensation. The remaining $3.2 million increase was primarily due to an increase in professional fees, expanding infrastructure costs and other administrative expenses.

We anticipate that our general and administrative expenses will continue to increase in future periods, reflecting both increased costs in connection with the potential future commercialization of gedatolisib, an expanding infrastructure, and increased professional fees associated with public company regulatory developments and requirements, and other compliance matters.

Interest Expense

Interest expense during the year ended December 31, 2025, was $17.1 million and represents an increase of $6.9 million, or 67%, compared to 2024. Interest expense in 2025 is attributable to the Notes and the A&R Loan Agreement, and in 2024 is attributable to the A&R Loan Agreement. The increase is primarily due to the incremental $61.7 million funding of the Term Loan C in May 2024, the issuance of $201.3 million aggregate principal amount of Notes in July 2025 and the $30.0 million distribution of the Term Loan D in September 2025. The $17.1 million of interest expense includes $4.2 million of non-cash interest expense.

Interest Income

Interest income during the year ended December 31, 2025 was $12.3 million and represents an increase of $0.5 million, or 5%, compared to 2024. The increase was primarily the result of a higher invested cash balance, partially offset by lower market interest rates.

Liquidity and Capital Resources

Liquidity

Since our inception, we have incurred losses and cumulative negative cash flows from operations. Through December 31, 2025, we have funded our operations primarily through private placements, registered offerings of our equity securities, convertible notes, and borrowings under loan agreements. From inception through December 31, 2025, we raised an aggregate of $506.8 million of net proceeds through sales of our securities, $194.9 million of net proceeds through the issuance of the Notes, and $130.0 million of gross proceeds through borrowings under loan agreements, not including payable-in-kind interest. As of December 31, 2025, our cash and cash equivalents and short-term investments were $165.7 million and $275.8 million, respectively, and we had an accumulated deficit of $448.9 million.

Capital Resources

To help meet our liquidity requirements, we have entered into various equity and financing arrangements. As of December 31, 2025, our material cash requirements for the operations of our business consisted primarily of the current and long-term liabilities noted on our balance sheets, as well as other commitments, including the following notable items:

	●	In July 2025, we issued and sold 2,172,368 Shares and Pre-Funded Warrants to purchase up to 400,000 shares of common stock pursuant to the Equity Underwriting Agreement with the Representatives of the Underwriters, resulting in net proceeds of $91.6 million (see Note 8. Stockholders' Equity).
	●	In August 2025, we issued $201.3 million aggregate principal amount of convertible notes, resulting in net proceeds of $194.9 million (see Note 10. Debt).
	●	During 2025 and 2024, investors exercised 5,282,375 and 1,827,357 warrants, net of shares withheld for exercise price, respectively, which generated $42.1 million and $14.7 million in cash, respectively (see Note 8. Stockholders' Equity).
	●	In February 2022, we entered into an Open Market Sale Agreement with Jefferies, as agent, pursuant to which we may offer and sell, from time to time, through Jefferies, shares of our common stock having an aggregate offering price of up to $50.0 million, which amount was subsequently increased to $400.0 million on January 9, 2026. In May 2024 and April 2024, we sold 149,700 and 285,714 shares of common stock, respectively, at an average selling price of $17.55 per share, generating net proceeds of $7.3 million after deducting commissions and other offering expenses of $0.3 million (see Note 8. Stockholders' Equity and Note 13. Subsequent Events).
	●	In May 2024, we issued and sold 3,871,000 shares of common stock pursuant to an underwriting agreement with Leerink Partners LLC, TD Securities (USA) LLC and Stifel, Nicolaus & Company, Incorporated, resulting in net proceeds of $56.3 million (see Note 8. Stockholders' Equity).
	●	In September 2025, we entered into the Third Amendment (the "Third Amendment") to the Amended and Restated Loan and Security Agreement (the "A&R Loan Agreement"); in July 2025, we entered into the Second Amendment to the A&R Loan Agreement; and in May 2025, we entered into the First Amendment to the A&R Loan Agreement. In May 2024, we entered into the A&R Loan Agreement, which amended and restated, in its entirety, the Loan and Security Agreement, dated April 8, 2021, as amended, between us and Innovatus, as collateral agent, and the Lenders named therein (the "Prior Loan Agreement").

In September 2025, we received funding of the $30.0 million Term D Loan (as defined in the Amended A&R Loan Agreement) upon achievement of the Term D Milestone (as defined in the Amended A&R Loan Agreement), resulting in net proceeds of $27.7 million. In connection with the funding of the Term D Loan, we issued warrants with an exercise price of $14.84 per share to purchase an aggregate of 50,537 shares of our common stock to Innovatus, Oxford, and certain of its affiliates. Subsequent to the Third Amendment, we may draw (i) up to $100.0 million under Term E Loan (as defined in the Amended A&R Loan Agreement) upon FDA approval of gedatolisib in second line wild-type ABC patients post CDK4/6 inhibitor therapy; (ii) up to three $40.0 million Term F Loans (as defined in the Amended A&R Loan Agreement), for a total of $120.0 million, upon achievement of certain trailing three months' product revenue thresholds; and (iii) up to $150.0 million Term G Loan (as defined in the Amended A&R Loan Agreement), which continues to be available only in the Lenders' sole discretion upon our request. The term loans include financial covenants related to liquidity and other financial measures and have a maturity date of November 1, 2029.

In May 2024, we received funding of the first $100 million under the A&R Loan Agreement, including tranche payments of $16.8 million (the "Term A Loan") and $21.5 million (the "Term B Loan") reflecting repayment of the principal amount of loans under the Prior Loan Agreement plus accrued payment-in-kind interest, in addition to $61.7 million of new borrowings (the "Term C Loan"), resulting in net proceeds of $59.2 million. In connection with the funding of the Term C Loan, we issued warrants with an exercise price of $14.84 per share to purchase an aggregate of 103,876 shares of our common stock to Innovatus and Oxford (see Note 10. Debt).

Liquidity and capital resource requirements

We expect that our research and development and general and administrative expenses will increase as we continue to develop gedatolisib, conduct the VIKTORIA-1 Phase 3 clinical trial, the CELC-G-201 Phase 1b/2 trial, and the VIKTORIA-2 Phase 3 clinical trial, conduct other studies and clinical trials, and pursue other business development activities. We would also expect to scale sales and marketing expenses as we prepare for commercial launch and then commercialize gedatolisib. We expect to use cash on hand, together with the funds received or to be received under the debt and equity financings described above, to fund our research and development expenses, clinical trial costs, capital expenditures, working capital, sales and marketing expenses, and general corporate expenses.

Based on our current business plan, we believe that our current cash, cash equivalents and short-term investments, together with available borrowings under the Amended A&R Loan Agreement, will provide sufficient cash to finance our operations through 2027.

Our expectations as to how long our current capital resources will be sufficient to fund our operations are based on assumptions that may not be accurate, and we could use our current capital resources sooner than we currently expect. In addition, we may seek to raise additional capital to finance capital expenditures and operating expenses over the next several years as we seek to obtain approval for and launch gedatolisib; expand our infrastructure, commercial operations and research and development activities; and take advantage of financing or other opportunities that we believe to be in the best interests of the Company and our stockholders. Additional capital may be raised through the sale of common or preferred equity or convertible debt securities, entry into debt facilities or other third-party funding arrangements. The sale of equity and convertible debt securities may result in dilution to our stockholders and those securities may have rights senior to those of our common stock. Agreements entered into in connection with such capital raising activities could contain covenants that would restrict our operations or require us to relinquish certain rights. Additional capital may not be available on reasonable terms, or at all.

Cash Flows

The following table summarizes the primary sources and uses of cash and cash equivalents (in thousands):

		Year Ended December 31,
		2025				2024
Net cash and cash equivalents (used in) provided by:
Operating activities		$	(153,280	)		$	(83,467	)
Investing activities			(64,084	)			(63,069	)
Financing activities			360,552				138,388
Net increase (decrease) in cash and cash equivalents		$	143,188			$	(8,148	)

Operating Activities

Net cash used in operating activities was $153.3 million during the year ended December 31, 2025, and consisted of a net loss of $177.0 million and working capital changes of $2.7 million, partially offset by non-cash expenses of $26.4 million. The $2.7 million decrease in working capital consisted of a $15.4 million increase in accrued expenses, partially offset by a $15.1 million increase in prepaid expenses and other current and non-current assets and a $3.0 million decrease in accounts payable. The $26.4 million of non-cash expenses consisted of $21.4 million of stock-based compensation expense, net non-cash interest income and expense of $4.8 million, and depreciation expense of $0.2 million.

Net cash used in operating activities was $83.5 million during the year ended December 31, 2024, and consisted of a net loss of $111.8 million, partially offset by working capital changes of $18.3 million and non-cash expenses of $10.0 million. The $18.3 million increase in working capital consisted of a $13.2 million increase in accrued expenses, a $4.3 million increase in accounts payable, and a $0.8 million decrease in prepaid expenses and other current and non-current assets. The $10.0 million of non-cash expenses consisted of $7.0 million of stock-based compensation expense, net non-cash interest income and expense of $2.9 million, and depreciation expense of $0.1 million.

Investing Activities

Net cash used in investing activities was $64.1 million during the year ended December 31, 2025, and consisted of $63.9 million of net purchases of short-term investments in U.S. treasury securities and $0.2 million in purchases of property and equipment.

Net cash used in investing activities was $63.1 million during the year ended December 31, 2024, and consisted of $62.8 million of net purchases of short-term investments in U.S. treasury securities and $0.3 million in purchases of property and equipment.

Financing Activities

Net cash provided by financing activities was $360.6 million during the year ended December 31, 2025, and consisted primarily of net proceeds of $195.0 million from the Note Offering, $91.6 million from the Equity Offering, and $27.7 million from the Term D Loan. In addition, cash provided by financing activities consisted of proceeds of $42.1 million from the exercise of common stock warrants and $4.2 million from the exercise of employee stock options and employee stock purchases.

Net cash provided by financing activities was $138.4 million during the year ended December 31, 2024, and consisted primarily of net proceeds of $59.2 million from the Term C Loan incremental funding, $56.3 million from an equity offering, and $7.3 million from the at-the-market offering. In addition, cash provided by financing activities consisted of proceeds of $14.7 million from the exercise of common stock warrants and $1.1 million from the exercise of employee stock options and employee stock purchases, partially offset by $0.2 million of secondary registration statement costs.

RECENT ACCOUNTING PRONOUNCEMENTS

From time-to-time new accounting pronouncements are issued by the Financial Accounting Standards Board or other standard setting bodies and adopted by us as of the specified effective date. Unless otherwise discussed in Note 2 to our financial statements included elsewhere in this Annual Report, we believe that the impact of recently issued standards that are not yet effective will not have a material impact on our financial position or results of operations upon adoption.

CRITICAL ACCOUNTING POLICIES AND USE OF ESTIMATES

Our management's discussion and analysis of financial condition and results of operations is based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States, or Generally Accepted Accounted Principles ("U.S. GAAP"). The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses during the reporting periods. These items are monitored and analyzed by us for changes in facts and circumstances, and material changes in these estimates could occur in the future. We base our estimates on historical experience and on various other factors that we believe are reasonable under the circumstances; the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Changes in estimates are reflected in reported results for the period in which they become known. Actual results may differ materially from these estimates.

Our significant accounting policies are more fully described in Note 2 to our financial statements included elsewhere in this Annual Report. Of our significant accounting policies, we believe that the following reflect the critical accounting estimates used in the preparation of our financial statements:

Stock-Based Compensation

Stock-based compensation expense represents the cost of the grant date fair value of equity awards recognized over the requisite service period of the awards (generally the vesting period) on a straight-line basis with forfeitures recognized as they occur.

We estimate the fair value of option grants using the Black-Scholes option-pricing model and the fair value of awards with market-based vesting conditions using the Monte Carlo simulation model. Estimating the fair value of equity awards using these valuation models is affected by assumptions regarding a number of variables, including the expected stock price volatility, the expected term of the award, the risk-free interest rate, expected dividends, and the price per share of our common stock on the grant date. Changes in these assumptions can materially affect the fair value and ultimately how much stock-based compensation expense is recognized. These inputs are subjective and generally require significant analysis and judgment to develop.

Clinical Trial Costs

We record prepaid or accrued clinical trial costs conducted by third-party service providers, which includes the conduct of clinical trials. These costs can be a significant component of our research and development expenses. We use progress reports from third-party service providers, including the respective invoicing, to record actual expenses, along with determining changes to prepaid or accrued clinical trial costs. With the ongoing clinical trials, our estimated expenses in future periods and actual services performed may vary from these estimates, and these estimates may become more significant. Changes in these estimates that result in material changes to our prepaid or accrued clinical trial costs could materially affect our results of operations and financial position.