CELC US Equity☆

UNITED

STATES

SECURITIES

AND EXCHANGE COMMISSION

Washington,

D.C. 20549

FORM

10-K

(Mark

One)

For

the fiscal year ended December 31, 2025

or

For

the transition period from _______________________ to ___________________

Commission

File Number: 001-38207

Celcuity

Inc.

(Exact

name of registrant as specified in its charter)

(Address of principal executive offices) (Zip Code)

Registrant’s

telephone number, including area code: (763)392-0767

Securities

registered pursuant to Section 12(b) of the Act:

Title of each class Trading Symbol(s) Name of each exchange on which registered

Common Stock, $0.001 par value per share CELC The Nasdaq Stock Market LLC

Securities

registered pursuant to Section 12(g) of the Act:

None

Indicate

by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. ☒ Yes ☐ No

Indicate

by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. ☐ Yes ☒

No

Indicate

by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)

has been subject to such filing requirements for the past 90 days. ☒ Yes ☐ No

Indicate

by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule

405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant

was required to submit such files). ☒ Yes ☐ No

Indicate

by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting

company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,”

“smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.:

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☐

If

an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying

with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate

by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness

of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 262(b)) by the registered

public accounting firm that prepared or issued its audit report. ☐

If

securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant

included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate

by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation

received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate

by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). ☐ Yes ☒ No

The

aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant, based on $13.35, the closing

price of the shares of common stock on June 30, 2025 (the last business day of the registrant’s most recently completed second

fiscal quarter) as reported by The Nasdaq Capital Market on such date, was approximately $457,485,677.

As

of March 17, 2026, there were 48,336,675 shares of the registrant’s common stock outstanding.

DOCUMENTS

INCORPORATED IN PART BY REFERENCE

Portions

of the registrant’s definitive proxy statement relating to its 2026 Annual Meeting of Stockholders are incorporated by reference

into Part III of this Annual Report on Form 10-K.

2025

Annual Report on Form 10-K

Table

of Contents

Page

PART I

Item 1. Business 7

Item 1A. Risk Factors 30

Item 1B. Unresolved Staff Comments 51

Item 1C. Cybersecurity 51

Item 2. Properties 53

Item 3. Legal Proceedings 53

Item 4. Mine Safety Disclosures 53

PART II

Item 6. Reserved 54

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 64

Item 8. Financial Statements and Supplementary Data 65

Item 9A. Controls and Procedures 91

Item 9B. Other Information 91

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 91

PART III

Item 10. Directors, Executive Officers and Corporate Governance 92

Item 11. Executive Compensation 92

Item 14. Principal Accountant Fees and Services 92

PART IV

Item 15. Exhibits and Financial Statement Schedules 92

Signatures 93

SPECIAL

NOTE REGARDING FORWARD-LOOKING STATEMENTS

The

Private Securities Litigation Reform Act of 1995 provides a “safe harbor” for forward-looking statements. This

Annual Report on Form 10-K (this “Annual Report”) contains forward-looking statements regarding us, our business prospects

and our results of operations that are subject to certain risks and uncertainties that could cause our actual business, prospects and

results of operations to differ materially from those that may be anticipated by such forward-looking statements. Factors that could

cause or contribute to such differences include, but are not limited to, those described in Part I, Item 1A, “Risk Factors”

and elsewhere in this Annual Report. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak

only as of the date of this Annual Report. We expressly disclaim any intent or obligation to update or revise any forward-looking statements,

whether as a result of new information, future events or otherwise. Readers are urged to carefully review and consider the various disclosures

made by us in this Annual Report and in our other reports filed with the Securities and Exchange Commission (the “SEC”) that

advise interested parties of the risks and uncertainties that may affect our business.

All

statements, other than statements of historical facts, contained in this Annual Report, including statements regarding our plans, objectives

and expectations for our business, operations and financial performance and condition, are forward-looking statements. In some cases,

you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,”

“could,” “estimate,” “expect,” “intend,” “may,” “might,” “ongoing,”

“plan,” “potential,” “predict,” “should,” “target,” “will,” “would,”

or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. Forward-looking

statements involve known and unknown risks, uncertainties and other factors that may cause our results, performance or achievements to

be materially different from the information expressed or implied by the forward-looking statements in this Annual Report. Additionally,

our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures

or investments that we may make. Forward-looking statements may include, among other things, statements relating to:

● our revenue expectations;

● our expectations as to the use of proceeds from our financing activities;

● our plans with respect to potentially raising capital; and

These

statements involve known and unknown risks, uncertainties and other factors that may cause our results or our industry’s actual

results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these

forward-looking statements. Certain risks, uncertainties and other factors include, but are not limited to, our limited operating history;

our potential inability to develop, validate, obtain regulatory approval for and commercialize gedatolisib on a timely basis or at all;

the uncertainties and costs associated with clinical studies and with developing and commercializing pharmaceuticals; the complexity

and difficulty of demonstrating the safety and sufficient magnitude of benefit to support regulatory approval of gedatolisib and other

products we may develop; challenges we may face in developing and maintaining relationships with pharmaceutical company partners, including

our current and any future suppliers of our product candidate; the uncertainty and costs associated with clinical trials; the uncertainty

regarding market acceptance by physicians, patients, third-party payors and others in the medical community, and with the size of market

opportunities available to us; difficulties we may face in managing growth, such as hiring and

retaining a qualified sales force and attracting and retaining key personnel; changes in government regulations; tightening credit markets

and limitations on access to capital; stock market volatility or other factors that may affect our ability to access capital on favorable

terms or at all; and obtaining and maintaining intellectual property protection for gedatolisib and time and expense associated with

enforcing our intellectual property rights against third parties, and defending third-party claims of intellectual property infringement,

investigations or litigation threatened or initiated against us. See “Risk Factors” in Part I, Item 1A of this Annual

Report for additional risks, uncertainties and other factors applicable to us.

SUMMARY

OF RISK FACTORS

Below

is a summary of the material factors that make an investment in our common stock speculative or risky. This summary does not address

all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, and other risks that we face,

can be found in the “Risk Factors” section of Part I, Item 1A of this Annual Report and should be carefully considered, together

with other information in this Annual Report and our other filings with the SEC before making investment decisions regarding our common

stock.

● We are dependent on our ability to attract and retain key personnel;

● The successful development of our products is highly uncertain;

● We face significant competition from other pharmaceutical companies;

PART

I

ITEM

1. Business

Overview

Unless

otherwise provided in this Annual Report, references to the “Company,” “we,” “us,” and “our”

and similar references refer to Celcuity Inc., a Delaware corporation. We own various unregistered trademarks and service marks, including

our corporate logo. Solely for convenience, the trademarks, trade names and service marks in this Annual Report, including those owned

by third parties, may be referred to without the ®,TM or SM symbols, but such references should

not be construed as any indicator that the owner of such trademarks, trade names and service marks will not assert, to the fullest extent

under applicable law, their rights thereto. We do not intend the use or display of other companies’ trademarks, trade names and

service marks to imply an endorsement or sponsorship of us by any other companies.

We

are a clinical-stage biotechnology company focused on the development of targeted therapies for the treatment of multiple solid

tumor indications. Our 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

January 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- ABC after progression on CDK4/6

therapy. Fast Track designation is granted by the FDA for products that are intended for the treatment of serious or life-threatening

diseases or conditions and which demonstrate the potential to address an unmet medical need.

In

July 2022, gedatolisib was granted Breakthrough Therapy designation for HR+/HER2- ABC after progression on CDK4/6 therapy. Breakthrough

Therapy designation is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended

to treat a serious or life-threatening condition. The criteria for Breakthrough Therapy designation requires preliminary clinical evidence

that demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapy.

In

December 2022, we dosed the first patient in our Phase 3, open-label, randomized, two-part clinical trial, VIKTORIA-1. This trial is evaluating

the efficacy and safety of gedatolisib in combination with fulvestrant, with and without palbociclib, in adults with HR+/HER2- ABC who

have received prior treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor. Two studies based on PIK3CA

mutation status are included in the trial. According to confirmed PIK3CA mutation status, patients were manually assigned either

to a cohort evaluating patients who have PIK3CA WT tumors or to a cohort evaluating patients who have PIK3CA MT tumors.

The two cohorts were randomized separately. The cohort evaluating PIK3CA WT patients reported detailed study results in the third

and fourth quarters of 2025. The cohort evaluating patients with PIK3CA MT tumors has completed enrollment, and topline data is

expected to be available in the second quarter of 2026.

In

February 2024, we dosed our first patient in our Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with

darolutamide in patients with mCRPC. Initial preliminary data for the Phase 1 portion of the trial were reported in the fourth

quarter of 2025.

During

the third quarter of 2024, we commenced site selection and activation activities to support a Phase 3, open-label, randomized

clinical trial, VIKTORIA-2, 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. The first patient was dosed in July 2025. For

the CDK4/6 inhibitor, investigators may choose either ribociclib or palbociclib. This multi-center, international trial enrolled 35

evaluable 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.

In

August 2025, the FDA granted our request to submit our NDA for gedatolisib under the FDA’s Real-Time Oncology Review (“RTOR”)

program based on data from the PIK3CA WT cohort of the Phase 3 VIKTORIA-1 clinical trial. We made our first NDA pre-submission

in September 2025 and completed our submission of the NDA in November 2025. The FDA accepted our NDA on January 16, 2026, designating

it for Priority Review, with a target user fee goal date of July 17, 2026, pursuant to the Prescription Drug User Fee Act (“PDUFA”)

VII.

The

PI3K/AKT/mTOR (PAM) Pathway

Dysregulation

of the PAM signaling pathway is observed in many types of cancer, including breast and prostate cancer. The important role the PAM pathway

plays in cancer has led to significant investment in the development of many different PI3K and mTOR inhibitors for solid tumors.

Activities

associated with PI3K involve complex essential cell regulatory mechanisms, including feedforward and feedback signaling loops.

Overactivation of the pathway is frequently present in human malignancies and plays a key role in cancer progression. Four catalytic

isoforms of class I PI3K preferentially mediate signal transduction and tumor cell survival based on the type of malignancy and the

genetic or epigenetic alterations an individual patient harbors. Due to the multiple subcellular locations, activities, and

importance of the different PI3K complexes in regulating many types of cancer cell proliferation, control of PI3K activity is an

important target in cancer therapy.

mTOR

is a critical effector in cell-signaling pathways commonly dysregulated in human cancers. The mTOR signaling pathway integrates both

intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation, and survival. mTOR

is a serine/threonine protein kinase, a downstream effector of PI3K, and regulated by hormones, growth factors, and nutrients, that are

contained in two functionally distinct protein assemblies – mTORC1 and mTORC2. In cancer, dysfunctional signaling leads to various

constitutive activities of the mTOR complexes, making mTOR a good therapeutic target.

Developing

efficacious and well-tolerated therapies that target this pathway has been challenging. This reflects the inherent adaptability and complexity

of the PAM pathway, where numerous feedforward and feedback loops, crosstalk with other pathways, and compensatory pathways enable resistance

to PAM pathway inhibition. Another major hurdle for the development of PAM pathway inhibitors has been the inability to achieve optimal

drug-target blockade in tumors while avoiding undue toxicities in patients.

Gedatolisib

By

inhibiting multiple components of the PAM pathway, gedatolisib can overcome adaptive resistance mechanisms that inhibitors of single

PI3K/AKT/mTOR components do not address. As a result, we believe gedatolisib offers distinct advantages over currently approved and investigational

therapies that target PI3Kα, AKT or mTORC1 alone or together.

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 the

mTORC1 and mTORC2 complexes, as getatolisib 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.

To

compare the functional effect of inhibiting single versus multiple PAM pathway components, we evaluated gedatolisib, and component-selective

inhibitors for PI3Kα (alpelisib), AKT (capivasertib) and mTORC1 (everolimus) in a panel of breast cancer cell lines using a live

cell proliferation rate dose response analysis. The results of this analysis are presented in the table below.

Breast

Cancer Cell Line Proliferation Rate Dose Response Analysis

Average

values for 14 PIK3CA MT and 14 PIK3CA WT breast cancer cell lines

Note:

Growth rate (“GR”) was assessed using 28 cell lines by measuring live cells reducing potential with Real Time-Glo MT luciferase

assay before and after 72-hour drug treatment. GR50 (concentration required to inhibit growth rate by 50%) is a measure of potency. Max

cell growth inhibition (GR at highest drug concentration tested) is a measure of efficacy.

Source:

Rossetti S. et.al., npj Breast Cancer, 2024

On

average, gedatolisib was at least 300-fold more potent on average than the single component PAM inhibitors analyzed and only gedatolisib

induced a significant cytotoxic effect. In addition, gedatolisib’s potency and efficacy was comparable in cell lines with and without

PIK3CA mutations, in contrast to the single component PAM inhibitors.

● Better tolerated by patients than oral PI3K and mTOR drugs.

Gedatolisib

is administered intravenously (“IV”) on a four-week cycle of once a week for three weeks, then 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 still leads to challenging toxicities. The experience with the FDA approved oral PI3Kα inhibitor,

alpelisib, and mTORC1 inhibitor, everolimus, illustrates the challenge. In their Phase 3 pivotal trials, alpelisib and everolimus

were found to induce hyperglycemia in 79% and 69% of patients evaluated, respectively. In addition, 26% and 24% of patients

discontinued alpelisib and everolimus, respectively, due to treatment related adverse events. 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.

Clinical

Development

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.

Breast

Cancer Program

Breast

cancer is the most prevalent cancer in women, accounting for 30% of all female cancers and 7% of cancer-related deaths in the United

States. The National Cancer Institute estimated that approximately 316,950 new cases of breast cancer would be diagnosed in the United

States in 2025, and approximately 42,170 breast cancer patients would die of the disease.

Four

different breast cancer subtypes are currently identified using molecular tests that determine the level of HR and HER2 expression. The

most common subtype of ABC is HR+/HER2-. Approximately 70% of all breast cancer tumors express the estrogen receptor (“ER”),

which, upon activation, regulates the expression of various genes involved in tumor proliferation. Despite progress in treatment strategies,

HR+/HER2- advanced or metastatic breast cancer remains an incurable disease, with a median overall survival (OS) of three years and a

five-year survival rate of 34%.

Three

different classes of targeted therapies are currently used to treat HR+/HER2- tumors: endocrine-based therapies, CDK4/6 inhibitors, and

PAM inhibitors. Each of the CDK4/6 inhibitors and PAM inhibitors are generally used to respond to the related mechanisms of resistance

to endocrine therapy, namely, activation of the CDK4/6 and PAM pathways.

Nearly

80% of breast cancers have direct or indirect activation of the PAM pathway. The upregulation of the PAM pathway promotes hormone-dependent

and independent ER transcriptional activity, which contributes to endocrine resistance, leading to tumor cell growth, survival, motility,

and metabolism. Clinical studies have demonstrated that PAM inhibition can restore sensitivity to endocrine therapy (ET).

Additionally,

the PAM pathway, like other mitogenic pathways, can also promote the activities of cyclin D and CDK4/6 to drive proliferative cell cycling.

The available evidence indicates that resistance to CDK4/6 inhibition in patients with HR+/HER2- ABC is a transient adaptive mechanism,

most likely involving the PAM pathway. This data indicates that CDK4/6 signaling may be restored in CDK4/6 resistant tumors when PAM

inhibitors are applied. Thus, continuing CDK4/6 inhibitor treatment in combination with a PAM inhibitor in patients who progressed on

their prior CDK4/6 inhibitor, would both blockade the potentially reactivated CDK4/6 pathway and prevent adaptive activation of the PAM

pathway. This suggests the limited efficacy induced by current standard-of-care (SOC) therapies in patients who have progressed on a

CDK4/6 therapy reflects the mechanistic inadequacy of relying on partial PAM inhibition (e.g., alpelisib or everolimus) and no CDK4/6

inhibition to address this complex disease mechanism.

We

believe the complex connection between the PAM and CDK4/6 pathways can potentially enable gedatolisib to adaptively reactivate CDK4/6

signaling that reportedly occurs in CDK4/6 resistant tumors when the PAM pathway is comprehensively inhibited. By re-activating CDK4/6

signaling, we believe gedatolisib can restore the therapeutic effect of CDK4/6 inhibition when it is combined with a CDK4/6 inhibitor.

The contributory effect of a CDK4/6 inhibitor when combined with gedatolisib would thus largely reflect the interaction between the two

therapies that gedatolisib initiates.

Evidence

of gedatolisib’s anti-tumor activity in breast cancer cells was provided in a study evaluating the MCF7 xenograft model (ER+/HER2-/PIK3CA

mutant), where the combination of gedatolisib with palbociclib and fulvestrant caused 90% tumor regression with no tumor regrowth observed

for more than 60 days after the final dose.

Source:

Layman SABCS 2021

Clinical

Experience with Gedatolisib in Breast Cancer

The

favorability of preliminary results from a Phase 1b clinical trial (B2151009, further described below) which evaluated 138 patients

with HR+/HER2- ABC led us to focus our initial clinical development program on ABC.

On

January 13, 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- ABC after progression on

CDK4/6 therapy. Fast Track designation is granted by the FDA for products that are intended for the treatment of serious or life-threatening

diseases or conditions and which demonstrate the potential to address an unmet medical need. The designation offers the opportunity for

frequent interactions with the FDA to discuss the drug’s development plan and to ensure collection of appropriate data needed to

support drug approval, as well as eligibility for rolling submission of an NDA.

On

July 18, 2022, gedatolisib was granted Breakthrough Therapy designation for HR+/HER2- ABC after progression on CDK4/6 therapy. Breakthrough

Therapy designation is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended

to treat a serious or life-threatening condition. The criteria for Breakthrough Therapy designation require preliminary clinical evidence

that demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapies.

The benefits of Breakthrough Therapy designation include more intensive guidance from the FDA on an efficient development program, access

to a scientific liaison to help accelerate review time, and potential eligibility for Priority Review if relevant criteria are met. Our

breakthrough application was supported by data from a Phase 1b clinical trial that assessed the safety, tolerability and clinical activity

of gedatolisib in combination with palbociclib and fulvestrant in patients with HR+/HER2- ABC whose disease progressed during treatment

with a CDK4/6 therapy and an aromatase inhibitor.

Phase

3 HR+/HER2- ABC Clinical Trial (VIKTORIA-1)

In

2022, we initiated VIKTORIA-1, a Phase 3, open-label, randomized clinical trial to evaluate the efficacy and safety of gedatolisib in

combination with fulvestrant with or without palbociclib in adults with HR+/HER2- ABC whose disease has progressed after prior CDK4/6

therapy in combination with an aromatase inhibitor. This multi-center, international trial has completed enrollment of 754 subjects at

nearly 200 clinical sites across North America, Europe, Latin America, and Asia-Pacific. The first patient was dosed in December 2022.

The

clinical trial is separately evaluating subjects according to their PIK3CA status.

The

clinical trial primary endpoints are progression free survival (“PFS”), per RECIST 1.1 criteria, as assessed by blinded independent central review (“BICR”).

Two primary endpoints will be evaluated in subjects who are PI3KCA WT, and one primary endpoint will be evaluated in subjects

who are PI3KCA MT. In subjects who are PI3KCA WT, the PFS of gedatolisib in combination with palbociclib and fulvestrant

(Arm A) will be compared to fulvestrant monotherapy (Arm C), and the PFS in gedatolisib in combination with fulvestrant (Arm B) will

be compared to fulvestrant monotherapy (Arm C). In subjects who are PI3KCA MT, the PFS of gedatolisib in combination with palbociclib

and fulvestrant (Arm D) will be compared to alpelisib combined with fulvestrant (Arm E).

All

subjects will receive treatment according to the assigned study arm until objective progressive disease, unacceptable toxicity, death,

or withdrawal of consent, whichever occurs first. Subjects in Arm C will have the option to receive the treatment regimen provided in

Arm A or Arm B upon radiographically confirmed disease progression. Subjects will be followed for adverse events, safety laboratory testing,

tumor assessment by RECIST v1.1, quality of life, and overall survival.

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 European Society of Medical Oncology (“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

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

ABC:

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.

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.

With

these results, the gedatolisib regimens represent a potential new 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.

B2151009 Phase

1b HR+/HER2- ABC Clinical 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.

Source:

Layman SABCS 2021

● Safety analysis:

● 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

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

WT MT WT MT WT MT WT MT

(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

Phase

3 HR+/HER2- ABC Clinical Trial (VIKTORIA-2)

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 35 evaluable 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.

Prostate

Cancer Program

In

the United States, prostate cancer is the second leading cause of cancer death in men. Current estimates predict that one in eight men

will be diagnosed with prostate cancer in his lifetime. The National Cancer Institute estimated that in 2025 there would be over 313,780

new cases of prostate cancer in the United States and approximately 35,770 deaths from the disease. Although approximately 69% of patients

are diagnosed with localized prostate cancer, about 8% of patients present with metastatic disease with a 5-year survival rate of 38%.

Androgen deprivation therapy (“ADT”) via medical or surgical castration has been the mainstay treatment for metastatic prostate

cancer. However, prostate cancer cells develop resistance to ADT and progress to castration resistance, leading to poor prognosis and

a median overall survival of about three to five years.

Men

with mCRPC have a poor prognosis and a predicted survival rate of fewer than two years from the initial time of progression. Treatment

options for prostate cancer depend on many different factors, including the stage of the cancer. Castration-resistant prostate cancer

is defined by disease progression despite ADT and is often indicated by rising levels of PSA. Current standard of care for men with castration-resistant

prostate cancer provides that patients should initially receive a combination of ADT and either abiraterone, which works by decreasing

androgen levels, or enzalutamide, which works by blocking androgen binding to androgen receptors (“AR”). If the disease progresses

despite these second-generation hormonal therapies, chemotherapy is considered the next treatment option. Treatment with chemotherapy

is generally postponed for as long as possible due to the potential for severe side effects including neuropathies, nausea, diarrhea,

decreased mental capacity and increased risk of infections.

Preclinical

studies have demonstrated a potential association between the PAM pathway and AR signaling in prostate cancer cells developing resistance

to ADT. In these studies, the AR and PAM pathways were shown to cross-regulate each other. This is similar to the relationship demonstrated

in breast cancer with the estrogen receptor pathway and the PAM pathway. Additionally, 70% - 100% of mCRPC tumors have PAM related pathway

alterations.

Several

clinical studies have shown promising results by inhibiting the PAM pathway in combination with an AR inhibitor. In separate Phase 2

and Phase 3 trials, the AKT inhibitor, ipatasertib, showed improvement in radiographic PFS (“rPFS”) in patients with mCRPC

and tumors with phosphatase and tensin homolog (“PTEN”) loss when ipatasertib was combined with the AR inhibitor, abiraterone,

versus abiraterone alone. In a Phase 2 trial, the pan-PI3K inhibitor, samotolisib, reported median rPFS of 10.2 when combined with enzalutamide

versus 5.5 months for enzalutamide alone.

Evidence

of gedatolisib’s in vivo activity in prostate cancer was provided in a study evaluating the 22RV-1, PC3, and enzalutamide sensitive

model (“C4-2”) prostate cancer xenograft models. As seen in the figures below, gedatolisib induced greater than 80% tumor

growth inhibition, regardless of the xenograft model’s sensitivity to the AR inhibitor, enzalutamide and the cell lines’

PTEN or AR status. In addition, gedatolisib combined with enzalutamide induced significantly greater tumor growth inhibition than enzalutamide

alone in the C4-2.

Source:

Sen, ASCO-GU, 2023

Phase

1b/2 mCRPC Clinical Trial (CELC-G-201)

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 AR inhibitor. We

dosed our first patient 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, we enrolled 38 participants 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.

Updated

clinical results from the Phase 1 portion of the clinical trial were presented at the ESMO congress in October 2025. The Phase 1 data

set utilized an August 15, 2025 data cut-off. Median duration of follow-up was 9.0 months.

The

six-month 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.

Pfizer

Gedatolisib License Agreement

In

April 2021, we entered into a license agreement (the “Gedatolisib License Agreement”) with Pfizer pursuant to which we acquired

exclusive (including as to Pfizer) worldwide sublicensable rights to research, develop, manufacture, and commercialize gedatolisib for

the treatment, diagnosis and prevention of all diseases. Pursuant to the Gedatolisib License Agreement, we are obligated to use commercially

reasonable efforts to develop and seek regulatory approval for at least one product in the U.S. and if regulatory approval is obtained,

to commercialize such product in the U.S. and at least one international major market.

We

paid Pfizer a $5.0 million upfront fee upon execution of the Gedatolisib License Agreement and issued 349,406 shares of our common

stock to Pfizer pursuant to an Equity Grant Agreement. We are also required to make milestone payments to Pfizer upon achievement of

certain development and commercial milestone events, including a $5.0 million milestone payment we made in January 2026 following

FDA acceptance of our NDA submission, up to an aggregate of $335.0 million. We will pay Pfizer tiered royalties on sales of

gedatolisib at percentages ranging from the low to mid-teens, that may be subject to deductions for expiration of valid claims,

amounts due under third-party licenses and generic competition. Unless earlier terminated, the Gedatolisib License Agreement will

expire upon the expiration of all royalty obligations. The royalty period will expire on a country-by-country basis upon the later

of (a) 12 years following the date of First Commercial Sale of such Product in such country, (b) the expiration of all regulatory or

data exclusivity in such country for such Product, or (c) the date upon which the manufacture, use, sale, offer for sale or

importation of such Product in such country would no longer infringe, but for the license granted herein, a Valid Claim of a

Licensed Patent Right. Capitalized terms in this paragraph have the meanings set forth in the Gedatolisib License

Agreement.

We

have the right to terminate the Gedatolisib License Agreement for convenience upon 90 days’ prior written notice. Pfizer may not

terminate the agreement for convenience. Either we or Pfizer may terminate the Gedatolisib License Agreement if the other party is in

material breach and such breach is not cured within the specified cure period. In addition, either we or Pfizer may terminate the Gedatolisib

License Agreement in the event of specified insolvency events involving the other party.

Formulation,