CELC US Equity☆

Item 1A. Risk Factors 26

Item 1B. Unresolved Staff Comments 46

Item 1C. Cybersecurity 46

Item 2. Properties 47

Item 3. Legal Proceedings 47

Item 4. Mine Safety Disclosures 47

PART II

Item 6. Selected Financial Data 49

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 56

Item 8. Financial Statements and Supplementary Data 57

Item 9A. Controls and Procedures 77

Item 9B. Other Information 77

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 77

PART III

Item 10. Directors, Executive Officers and Corporate Governance 78

Item 11. Executive Compensation 80

Item 14. Principal Accounting Fees and Services 80

PART IV

Item 15. Exhibits, Financial Statement Schedules 81

Signatures 82

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,” “target,”

“ongoing,” “plan,” “potential,” “predict,” “project,” “should,”

“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;

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 and commercialize gedatolisib on a timely basis or at all; the uncertainties and costs associated

with clinical studies and with developing and commercializing biopharmaceuticals; 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; the complexity and timeline for development

of our CELsignia tests; the uncertainty regarding market acceptance of our products and services by physicians, patients, third-party

payors and others in the medical community, uncertainty with respect to the size of market opportunities available to us; uncertainty

regarding the pricing of drug products and molecular and other diagnostic products and services that compete or may compete with us;

uncertainty with insurance coverage and reimbursement for our products and services; the potential impact of public health matters on

our business and clinical study activities; difficulties we may face in managing growth, such as hiring and retaining key personnel;

changes in government regulations; costs to comply with evolving regulations; and obtaining and maintaining intellectual property protection

for our technology and time and expense associated with 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 the Company.

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 Securities and Exchange Commission before making investment

decisions regarding our common stock.

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

● We have not independently verified our estimated market opportunities;

● The price of our common stock may be volatile and fluctuate substantially.

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 potent, well-tolerated, small molecule reversible inhibitor, administered

intravenously, that selectively targets all Class I isoforms of phosphatidylinositol-3-kinase (PI3K) and the two mechanistic target of

rapamycin (mTOR) sub-complexes, mTORC1 and mTORC2. Gedatolisib’s mechanism of action and pharmacokinetic properties are highly

differentiated from other currently approved and investigational therapies that target PI3K or mTOR alone or together. We believe there

is significant potential for gedatolisib to address breast and prostate cancer tumors, and it has the potential to be used in other tumor

types where the PAM pathway is either: i) driving tumorigenesis directly; ii) cooperating with other dysregulated signaling pathways;

or iii) a mechanism of resistance to other drug therapies.

We

obtained exclusive global development and commercialization rights to gedatolisib in April 2021 under a license agreement with Pfizer,

Inc. As of December 31, 2023, 492 patients with solid tumors have received gedatolisib in eight completed clinical trials. Gedatolisib’s

safety, tolerability and pharmacokinetic profile were determined in a Phase 1 First-in-Human study. Of the 492 patients, 129 were treated

with gedatolisib as a single agent in three clinical trials. The remaining 363 patients received gedatolisib in combination with other

anti-cancer agents in five clinical trials. Additional patients received gedatolisib in combination with other anti-cancer agents in

nine investigator sponsored clinical trials.

Our

initial clinical development programs for gedatolisib are focusing on the treatment of patients with hormone receptor positive (HR+),

human epidermal growth factor receptor 2 negative (HER2-), or HR+/HER2-, advanced or metastatic breast cancer and patients with metastatic

castration resistant prostate cancer (mCRPC).

In

January 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- metastatic breast cancer 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 disease 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- advanced breast cancer 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 clinical trial, VIKTORIA-1. This trial is evaluating

the efficacy and safety of two regimens in adults with HR+/HER2- advanced breast cancer whose disease has progressed after prior CDK4/6

therapy in combination with an aromatase inhibitor: 1) gedatolisib in combination with palbociclib and fulvestrant; and 2) gedatolisib

in combination with fulvestrant. Over two hundred clinical sites in North America, Europe, South America, Asia, and Australia are participating

in the study.

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.

The

PI3K/AKT/mTOR Pathway

Dysregulation

of the PI3K/protein kinase B (AKT)/mTOR, or 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 PI3K pathway, where numerous feedforward and feedback loops, crosstalk with other pathways, and compensatory pathways enable resistance

to PI3K inhibition. Another major hurdle for the development of PI3K pathway inhibitors has been the inability to achieve optimal drug-target

blockade in tumors while avoiding undue toxicities in patients.

Gedatolisib

By

targeting multiple nodes of the PAM pathway, gedatolisib can overcome adaptive resistance mechanisms that inhibitors targeting single

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

therapies that target PI3K or mTOR alone or together.

Gedatolisib

is a pan-class I isoform PI3K inhibitor with low nanomolar potency for the p110α, p110β, p110γ, and p110δ isoforms.

Because gedatolisib inhibits all four PI3K isoforms and both mTOR complexes, it 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. By contrast,

node-specific inhibitors cross-activate uninhibited sub-units due to numerous feedforward and feedback loops between the PI3K isoforms,

AKT, and mTOR, which in turn induces compensatory resistance that reduces the efficacy of isoform specific PI3K, pan-AKT, or single mTOR

kinase complex inhibitors.

To

compare the functional effect of inhibiting single versus multiple PAM pathway nodes, we evaluated gedatolisib, and node-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 SABCS 2023

On

average, gedatolisib was 300-fold more potent than the single node 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 node PAM inhibitors.

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

Gedatolisib

is administered intravenously (IV) 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, despite showing promising efficacy. By contrast, gedatolisib stabilizes at lower

concentration levels in plasma compared to orally administered PI3K inhibitors, resulting in less toxicity, while maintaining concentrations

sufficient to inhibit PI3K/mTOR signaling.

Isoform-specific

PI3K inhibitors administered orally were developed to reduce toxicities in patients. While the range of toxicities associated with isoform-specific

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 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 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 10%

discontinued treatment.

Clinical

Development

As

of December 31, 2023, 492 patients with solid tumors have received gedatolisib in eight completed clinical trials. Gedatolisib’s

safety, tolerability and pharmacokinetic profile were determined in a Phase 1 First-in-Human study. Of the 492 patients, 129 were treated

with gedatolisib as a single agent in three clinical trials. The remaining 363 patients received gedatolisib in combination with other

anti-cancer agents in five clinical trials. Additional patients received gedatolisib in combination with other anti-cancer agents in

nine investigator sponsored clinical trials.

Breast

Cancer Program

Breast

cancer is the most prevalent cancer in women, accounting for 30% of all female cancers and 13% of cancer-related deaths in the United

States. The National Cancer Institute estimated that approximately 298,000 new cases of breast cancer would be diagnosed in the United

States in 2023, and approximately 43,200 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 advanced breast cancer (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, metastatic HR+/HER2- breast cancer (MBC) remains an incurable disease, with a median overall survival (OS) of three

years and a five-year survival rate of 34%.

Four

different classes of targeted therapies are currently used to treat HR+/HER2- tumors: endocrine-based therapies, CDK4/6 inhibitors, PI3K

inhibitors and mTOR inhibitors. Each of the CDK4/6 inhibitors, PI3K inhibitors and mTOR inhibitors are generally used to respond to the

related mechanisms of resistance to endocrine therapy, namely, activation of the CDK4/6, PI3K and mTOR pathways.

Over

70% 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 PI3K and mTOR inhibition can restore sensitivity to estrogen 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- advanced breast cancer is a transient

adaptive mechanism, most likely involving the PI3K/mTOR pathway. This data indicates that CDK4/6 signaling is restored in CDK4/6 resistant

tumors when PI3K/mTOR inhibitors are applied. Thus, continuing CDK4/6 inhibitor treatment in combination with a PI3K/mTOR inhibitor in

patients who progressed on their prior CDK4/6 inhibitor, would both blockade the reactivated CDK4/6 pathway and prevent adaptive activation

of the PI3K/mTOR 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 PI3K/mTOR inhibition (e.g., alpelisib or everolimus)

and no CDK4/6 inhibition to address this complex disease mechanism.

We

believe the complex connection between the PI3K/mTOR and CDK4/6 pathways can enable gedatolisib to adaptively reactivate CDK4/6 signaling

that reportedly occurs in CDK4/6 resistant tumors when the PI3K/mTOR pathway is completely blockaded. 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 our most recently completed clinical trial, a Phase 1b study which evaluated 138 patients with

HR+/HER2- advanced breast cancer (ABC), led us to focus on our initial clinical development program on advanced breast cancer.

On

January 13, 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- metastatic breast cancer

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 disease 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 a New Drug Application.

On

July 18, 2022, gedatolisib was granted Breakthrough Therapy Designation for HR+/HER2- advanced breast cancer 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 therapy. 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. Celcuity’s breakthrough application was supported by data from a Phase 1b study that assessed the safety,

tolerability and clinical activity of gedatolisib in combination with palbociclib and fulvestrant in patients with HR+/HER2- advanced

breast cancer whose disease progressed during treatment with a CDK4/6 therapy and an aromatase inhibitor.

Phase

1b HR+/HER2- ABC Clinical Trial Results

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- advanced breast cancer. 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- advanced breast cancer were dosed in the clinical trial. Five patients from this study continue

to receive study treatment, as of December 31, 2023, each of whom have received study treatment for more than five years.

Analysis

for the 103 patients enrolled in the expansion portion of the Phase 1b clinical trial showed:

○ 64% objective response rate (ORR)

○ 92% clinical benefit rate (CBR)

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:

Wesolowski 2022 SABCS

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- advanced breast cancer whose disease has progressed

after prior CDK4/6 therapy in combination with an aromatase inhibitor. This multi-center, international trial is expected to enroll approximately

701 total subjects at more than 200 clinical sites across North America, Europe, Latin America, and Asia. The first patient was dosed

in December 2022.

The

clinical trial will enable separate evaluation of 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 AEs, safety laboratory testing, tumour

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

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 American Cancer Society estimates that in 2024 there will be over 299,000

new cases of prostate cancer in the United States and approximately 35,250 deaths from the disease. Although the majority of patients

are diagnosed with localized prostate cancer, about 6% of patients present with metastatic disease with a 5-year survival rate of 29%.

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 3 to 5 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 androgen deprivation therapy, or 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 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 androgen receptor (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 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 enzalutamide sensitive model (C4-2).

Source: Sen, ASCO-GU, 2023

Phase

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

We

received approval from the US 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

study (CELC-G-201) that will enroll up to 54 participants with mCRPC who progressed after treatment with an androgen receptor inhibitor.

We dosed our first patient in this trial in February 2024.

In

the Phase 1b portion of the study, Celcuity expects that 36 participants will be randomly assigned to receive 600 mg darolutamide combined

with either 120 mg gedatolisib in Arm 1 or 180 mg gedatolisib in Arm 2. An additional 12 participants will then be enrolled in the Phase

2 portion of the study at the recommended phase 2 dose (RP2D) level to enable evaluation of 30 participants treated with the RP2D of

gedatolisib.

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 of gedatolisib. The primary objective of the Phase 2 portion of the

trial is to assess the radiographic progression-free survival (rPFS) at six months of patients who received the RP2D.

Pfizer

License Agreement

In

April 2021, we entered into a license agreement, or 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 to Pfizer $5.0 million of our common

stock. We are also required to make milestone payments to Pfizer upon achievement of certain development and commercial milestone events,

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.

Manufacturing

We

rely on third parties to manufacture gedatolisib. We expect to enter into agreements with contract manufacturing organizations, or CMOs,

to produce drug substance for gedatolisib. We require all of our CMOs to conduct manufacturing activities in compliance with current

good manufacturing practice, or cGMP, requirements. We anticipate that these CMOs will have the capacity to support both clinical supply

and commercial-scale production, but we do not have any formal agreements at this time to cover commercial production. We may also elect

to enter into agreements with other CMOs to manufacture supplies of drug substance and finished drug product.

Sales

and Marketing

If

any of our product candidates are approved, we intend to market and commercialize them in the U.S. and select international markets,

either alone or in partnership with others. Cancer patients are managed by oncologists, medical geneticists and urologists, and therefore

we believe can be reached with a targeted sales force.

Competition

for Gedatolisib

The

pharmaceutical industry is characterized by rapid evolution of technologies and intense competition. While we believe that our product

candidates, technology, knowledge, experience and scientific resources provide us with competitive advantages, we face competition from

major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions,

among others. Any product candidates that we successfully develop and commercialize will compete with approved treatment options, including

off-label therapies, and new therapies that may become available in the future. Key considerations that would impact our ability to effectively

compete with other therapies include the efficacy, safety, method of administration, cost, level of promotional activity and intellectual

property protection of our products. Many of the companies against which we may compete have significantly greater financial resources

and expertise than we do in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory

approvals and marketing approved products.

There

are several PI3K, AKT, and mTOR inhibitors approved by the FDA, including Piqray and Afinitor from Novartis AG, Aliqopa from Bayer Corporation,

Copiktra from Verastem, Inc., Zydelig from Gilead Sciences, Inc. and Trucap from AstraZeneca plc. We are aware that other companies are,

or may be, developing products for this indication, including BridgeBio Inc., Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Kazia

Therapeutics Limited, Infinity Pharmaceuticals, Inc., Relay Therapeutics, Revolution Medicines Inc., Scorpion Therapeutics, Inc., and

Takeda Pharmaceutical Company Limited. There may be additional companies with programs suitable for addressing these patient populations

that could be competitive with our efforts but that have not yet disclosed specific clinical development plans. Smaller or early-stage

companies, including oncology-focused therapeutics companies, may also prove to be significant competitors, particularly through collaborative

arrangements with large and established companies. These companies may also compete with us in recruiting and retaining qualified scientific

and management personnel, establishing clinical trial sites, enrolling patients in clinical trials and acquiring technologies complementary

to, or necessary for, our programs. The availability of reimbursement from government and private payors will also significantly impact

the pricing and competitiveness of our products. Our competitors may obtain FDA or other regulatory approvals for their products more

rapidly than we may obtain approvals for our product candidates, which could result in our competitors establishing a strong market position

before we are able to commercialize our product candidates.

CELsignia

We

founded our company to develop our proprietary CELsignia diagnostic platform and relied on the capability of this technology to identify

our lead drug candidate, gedatolisib. CELsignia characterizes the specific activity of various oncogenic signaling pathways, including

the PAM pathway, in living patient tumor cells.

We

are supporting the advancement of new potential indications for three different targeted therapies, controlled by other pharmaceutical

companies, that would rely on a CELsignia companion diagnostic test to select patients. Our first analytically validated and commercially

ready test using our CELsignia platform, the CELsignia HER2 Pathway Activity Test for breast cancer, diagnoses two new sub-types of HER2-negative

breast cancer that traditional molecular diagnostics cannot detect. Our internal studies show that approximately 15-20% of HER2-negative

breast cancer patients have abnormal HER2 signaling activity similar to levels found in HER2-positive breast cancer cells. As a result,

these HER2-negative patients have undiagnosed HER2-driven breast cancer and would be likely to respond to the same anti-HER2 targeted

therapies only HER2-positive patients receive today. We have two interventional clinical trials underway to evaluate the efficacy of

HER2 targeted therapies in breast cancer patients selected with our CELsignia HER2 Pathway Activity Test.

Our

second CELsignia test for breast cancer evaluates independent c-Met signaling activity and its involvement with HER family signaling

in HER2-negative breast cancer tumor cells. Our internal studies show that approximately 20%-25% of HER2-negative breast cancer patients

have abnormal c-Met signaling activity that is co-activated with abnormal HER family signaling. These studies suggest that this sub-group

of HER2-negative breast cancer patients may best respond to treatment with a combination of HER family and c-Met inhibitors. We have

one interventional clinical trial underway to evaluate the efficacy of HER2 and c-Met targeted therapies, in previously treated metastatic

HER2-negative breast cancer patients selected with our CELsignia Multi-Pathway Activity Test, or CELsignia MP Test.

Our

third CELsignia test for breast cancer evaluates PI3K signaling in HER2-negative breast cancer tumor cells.

CELsignia

Clinical Trials

We

are currently collaborating on three Phase 2 clinical trials to evaluate the efficacy of our collaboration partners’ targeted therapies

in patients selected with one of our CELsignia tests. The goal of these trials is to support the development of three potential new drug

indications to treat patient groups found responsive by our CELsignia test to their approved targeted therapies. These clinical trials

include:

CELsignia’s

Competition

At

present, we are not aware of any other companies that offer diagnostic tests that use a patient’s live tumor cells to identify

the signaling pathway driving a patient’s cancer. There are several companies focused on developing genomic or proteomic analyses

of a patient’s diseased cells. Initial efforts identified protein targets or genetic mutations, oftentimes referred to as “biomarkers,”

that are associated with a disease process to enable development of drugs more closely tailored to specific patient populations.

As

tools for human genome analysis have become less expensive, a number of companies have also recently launched more complex genomic test

panels and gene expression signatures tests. These tests rely on a static measurement of molecular properties and mathematical analysis

to identify statistically significant correlations between the selected molecular properties and a clinical condition or outcome of populations

of patients with the “same” disease.

These

genetic tests often have limited predictive success because they only identify some, but not all, of, the molecular and cellular conditions

required for a drug therapy to function in a patient. They may identify the presence of the genes associated with a disease, but they

cannot determine how the gene products function in the context of a particular individual.

Providers

of genomic or proteomic tests include diagnostic kit manufacturers, hospitals, and independent laboratories. We do not plan to develop

tests where a molecular biomarker can identify drug responsive patients, so our current tests will not compete directly against the tests

provided by these other companies.

Diagnostics

competitors that have molecular method-based tests include, but are not limited to, Foundation Medicine, Caris Life Sciences, NeoGenomics,

LabCorp, Quest, Nanostring, Paradigm, Biocept, Exosome Diagnostics, Guardant Health, Roche Diagnostics, Qiagen, Myriad, and Genomic Health.

Principal

Suppliers for CELsignia

We

purchase commercially available reagents and instruments from a variety of suppliers. Our principal reagent suppliers include Bio-Techne

Corporation, Selleck Chemicals, Sigma-Aldrich, and VWR International. Our principal instrument suppliers include Agilent Technologies,

Integra Biosciences, Invitrogen, and Thermo Fisher Scientific. These items are purchased on a purchase order basis pursuant to the applicable

supplier’s standard terms and conditions. The items purchased from these suppliers are standard products sold widely to the biotechnology

industry. All items purchased are typically available within several days after an order is placed.

Intellectual

Property

Our

success depends in part on our ability to obtain and maintain proprietary protection for our product candidates, manufacturing and process

discoveries and other know-how, to operate without infringing the proprietary rights of others, and to prevent others from infringing

our proprietary rights. We plan to protect our proprietary positions using a variety of methods, which include protecting current U.S.

and foreign patents related to proprietary technology, inventions and improvements and prosecuting additional U.S. and foreign patents

that we determine are important to the development and implementation of our business. For example, we, our licensors, or our collaborators

currently have, or are pursuing, patents covering the composition of matter for our drug product candidates and we plan to generally

pursue patent protection covering methods-of-use for one or more clinical programs. We also rely on trade secrets, trademarks, know-how,

continuing technological innovation and potential in-licensing opportunities to develop and maintain our proprietary position.

Gedatolisib

Patents

We

entered into the Gedatolisib License Agreement with Pfizer in April 2021, pursuant to which we acquired exclusive worldwide rights

under Pfizer patents and know-how to develop, manufacture and commercialize gedatolisib. We have exclusive licenses under the

Gedatolisib License Agreement to patent rights in the U.S. and numerous foreign jurisdictions relating to gedatolisib. The patent

rights in-licensed under the Gedatolisib License Agreement include 11 granted patents in the U.S. and more than 290 patents granted

in foreign jurisdictions including Australia, Canada, China, France, Germany, Spain, United Kingdom and Japan. The U.S. patents

covering gedatolisib as a composition of matter have a statutory expiration date in May 2029. A U.S. composition of matter patent

that covers the lactic acid form of gedatolisib expires in December 2035. A pending U.S. application covering the cyclodextrin

formulation of gedatolisib that is currently in clinical development expires in June 2039, in each case, not including patent

term adjustment or any patent term extension, and relevant foreign counterparts.

CELsignia

Patents

With

respect to CELsignia, we have seven issued U.S. patents and more than 30 issued international patents covering our diagnostic

approach using cell signaling analysis in living patient cells to guide treatment of patients with targeted therapies and cell

sample preparation methods. The earliest expiration date of the patents is 2032. In addition, we have developed significant

proprietary know-how and trade secrets for the various cell sample preparation and cellular analysis methods we have

developed.

Trade

Secrets

In

addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position. We typically rely on trade

secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. We

protect trade secrets and know-how by establishing confidentiality agreements and invention assignment agreements with our employees,

consultants, scientific advisors, contractors and partners. These agreements generally provide that all confidential information developed

or made known during the course of an individual or entity’s relationship with us must be kept confidential during and after the

relationship. These agreements also generally provide that all inventions resulting from work performed for us or relating to our business

and conceived or completed during the period of employment or assignment, as applicable, shall be our exclusive property. In addition,

we take other appropriate precautions, such as physical and technological security measures, to guard against misappropriation of our

proprietary information by third parties.

Government

Regulation

Approval

of Gedatolisib and Other Drug Products

Government

authorities in the U.S. at the federal, state and local level and in other countries and jurisdictions, including the EU, extensively

regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage,

record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of drug

products, such as gedatolisib and other drugs that may be used in combination with or compete with gedatolisib. Generally, before a new

drug can be marketed, considerable data demonstrating its quality, safety and efficacy must be obtained, organized into a format specific

for each regulatory authority and submitted for review and approved by the regulatory authority. The regulatory approval process is time-consuming

and requires significant capital expenditures.

U.S.

Approval Process

Overview

of FDA Approval Process

In

the U.S., pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act, or the FDC

Act, and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture,

storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling,

and import and export of pharmaceutical products. Failure to comply with applicable U.S. requirements may subject a company to a variety

of administrative or judicial sanctions, such as FDA refusal to approve pending New Drug Applications, or NDAs, warning or untitled letters,

product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and

criminal prosecution. The process required by the FDA before a drug may be marketed in the United States generally involves the following:

● submission to the FDA of an NDA for a new drug;

The

lengthy process of seeking required approvals and the continuing need for compliance with applicable statutes and regulations require

the expenditure of substantial resources and approvals are inherently uncertain.

Preclinical

and Clinical Stages

Preclinical

tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as animal trials to assess the characteristics

and potential safety and efficacy of the product. The conduct of the preclinical tests must comply with federal regulations and requirements,

including good laboratory practices. The results of preclinical testing are submitted to the FDA as part of an IND along with other information,

including information about product chemistry, manufacturing and controls and a proposed clinical trial protocol. Long term preclinical

tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted. A 30-day waiting period

after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has neither commented

on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin.

The

clinical stage of development involves the administration of the investigational product to healthy volunteers or disease-affected patients

under the supervision of qualified investigators, generally physicians not employed by, or under control of, the trial sponsor, in accordance

with Good Clinical Practices, or GCPs. Clinical trials are conducted under protocols detailing, among other things, the objectives of

the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety

and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of an investigational

new drug application, or IND. Furthermore, each clinical trial must be reviewed and approved by an Institutional Review Board, or IRB,

for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical

trials are minimized and are reasonable in relation to anticipated benefits. The IRB also monitors the clinical trial until completed.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

A

registrational trial is a clinical trial that adequately meets regulatory agency requirements for the evaluation of a drug candidate’s

efficacy and safety such that it can be used to justify the approval of the drug. Generally, registrational trials are Phase 3 trials

but may be Phase 2 trials if the trial design provides a reliable assessment of clinical benefit, particularly in situations where there

is an unmet medical need.

Post-approval

trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to

gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow

up. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of a Biologics License

Application, or BLA.

Progress

reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse

events occur. The FDA or the sponsor may suspend or terminate a clinical trial at any time, or the FDA may impose other sanctions on

various grounds, including a finding that the research patients are being exposed to an unacceptable health risk. Similarly, an IRB can

suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with

the requirements of the IRB or if the drug has been associated with unexpected serious harm to patients.

There

also are requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries. Information

about most clinical trials must be submitted within specific timeframes for publication on the www.clinicaltrials.gov website. Information