What changed in this filing

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Item 1. Business

2023-03-23 compared with 2022-03-23 · 265 added, 337 removed, 1245 unchanged (33% of the section changed)

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

are a clinical-stage biotechnology company seeking to extend the lives of cancer patients by pursing an integrated therapeutic (Rx) and

companion diagnostic (CDx) strategy.

Our therapeutic efforts are focused on developing potential first-in-class or best-in-class molecularly

targeted therapies that address the same cancer driver a CELsignia companion diagnostic can identify.

CELsignia is uniquely able to analyze

live patient tumor cells to identify new groups of cancer patients likely to benefit from targeted therapies.

This enables a CELsignia

CDx to support advancement of new indications for already approved targeted therapies.

We believe this integrated Rx and CDx strategy

will maximize the impact our drug development efforts have on the treatment landscape for cancer patients.

first drug candidate we are developing internally is gedatolisib, a potent, well-tolerated, small molecule dual inhibitor, administered

intravenously, that selectively targets all class I isoforms of PI3K and mammalian target of rapamycin (mTOR).

In April 2021,

we obtained exclusive global development and commercialization rights to gedatolisib under a license agreement with Pfizer, Inc.

initial clinical development program for gedatolisib will focus on the treatment of patients with hormone receptor positive (HR+),

HER2-negative, advanced or metastatic breast cancer.

Additional clinical development programs are expected to focus on other tumor

types that involve a hormonal signaling pathway, such as prostate, endometrial, or ovarian cancer.

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

Our lead therapeutic candidate is gedatolisib, a pan-PI3K/mTOR inhibitor.

Its mechanism of action and pharmacokinetic properties are

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

to our CDx development activities, our CELsignia diagnostic platform is uniquely able to analyze live patient tumor cells to identify

new groups of cancer patients likely to benefit from targeted therapies.

therapeutic candidate, gedatolisib, is a potent, well-tolerated, small molecule dual inhibitor, administered intravenously, that selectively

targets all Class I isoforms of PI3K and mammalian target of rapamycin (mTOR).

In April 2021, we obtained exclusive global development

and commercialization rights to gedatolisib under a license agreement with Pfizer, Inc.

Our initial clinical development program for

gedatolisib will focus on the treatment of patients with hormone receptor positive (HR+), HER2-negative, advanced or metastatic breast

In 2022, we dosed our first patient in our Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant

with or without palbociclib in patients with HR+/HER2- advanced breast cancer (ABC).

the development of a potential first-in-class targeted therapy for breast cancer, like gedatolisib, with our CELsignia platform is a

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We exclusively licensed global rights to gedatolisib from Pfizer in April

A Phase 1b trial evaluating patients with HR+/HER2- metastatic breast cancer was initiated in 2016 and subsequently enrolled

138 patients.

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 the favorable preliminary results reported to date from the Phase 1b trial, we are preparing to initiate a Phase 3 clinical trial

(VIKTORIA-1) evaluating gedatolisib and fulvestrant with or without palbociclib in patients with HR+/HER2-

advanced or metastatic breast cancer whose disease progressed on prior treatment with a CDK4/6 therapy and an aromatase inhibitor.

expect to initiate the (VIKTORIA-1) study in the first half of 2022.

A Phase 1b trial evaluating patients with ER+/HER2- metastatic breast cancer was initiated in 2016 and subsequently enrolled 138

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.

July 18, 2022, gedatolisib was granted Breakthrough Therapy Designation for HR+/HER2- advanced breast cancer after progression on CDK4/6

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.

2022, we activated VIKTORIA-1, a Phase 3, open-label, randomized clinical trial to evaluate 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

1) gedatolisib in combination with palbociclib and fulvestrant;

and 2) gedatolisib in combination with fulvestrant.

clinical sites in North America, Europe, South America, Asia, and Australia have been selected to participate in the study.

clinical site was activated in the third quarter of 2022.

The first dosage of a patient in the trial occurred in December 2022.

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

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cases are for HR+/HER2- breast cancer.

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

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

70% of breast cancers are HR+/HER2-, which is indicative of hormone dependency.

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 29%.

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

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.

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.

specifically relates to gedatolisib, activation of the PI3K/mTOR pathway has been implicated in a wide variety of human cancers, involving

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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.

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.

is a critical effector in cell-signaling pathways commonly dysregulated in human cancers.

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alpelisib or everolimus) and no CDK4/6 inhibition to address this complex disease mechanism.

believe the complex connection between PI3K/mTOR and CDK4/6 regulated cell cycling 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.

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.

of gedatolisib anti-tumor in vivo activity was provided in a study evaluating the combination of gedatolisib and a CDK4/6 inhibitor in

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interaction that may occur with isoform-specific PI3K inhibitors and the confounding interaction between PI3K isoforms and mTOR.

This compares to therapies that only inhibit a single class I isoforms (e.g., alpelisib, a PI3K-α inhibitor)

or only one mTOR kinase complex (e.g., everolimus, an mTORC1 inhibitor), which cross-activate uninhibited sub-units due to numerous

feedforward and feedback loops between the PI3K isoforms and mTOR, which in turn induces compensatory resistance that reduces the

efficacy of isoform specific PI3K or single mTOR kinase complex inhibitors.

This compares to therapies that only inhibit a single Class I isoforms (e.g., alpelisib, a PI3K-α inhibitor) or only one mTOR

kinase complex (e.g., everolimus, an mTORC1 inhibitor), which cross-activate uninhibited sub-units due to numerous feedforward and

feedback loops between the PI3K isoforms and mTOR, which in turn induces compensatory resistance that reduces the efficacy of isoform

specific PI3K or single mTOR kinase complex inhibitors.

tolerated by patients than oral PI3K and mTOR drugs.

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anti-cancer agents in nine investigator sponsored clinical trials.

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.

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

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appropriate data needed to support drug approval, as well as eligibility for rolling submission of a New Drug Application.

July 18, 2022, gedatolisib was granted Breakthrough Therapy Designation for HR+/HER2- advanced breast cancer after progression on CDK4/6

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.

Gedatolisib’s

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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, led us to focus our initial clinical development program on advanced breast cancer.

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.

1 First-in-Human Study

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received doses of gedatolisib and the MTD was determined to be 154 mg IV once weekly (n = 42).

Subsequent analysis determined that the

recommended Phase 2 dose could be increased to 180 mg IV once weekly.

the MTD, the majority of patients enrolled in the MTD group experienced only grade 1 treatment-related adverse events (AEs).

3 treatment-related adverse events were noted in 23.8% of patients, and the most frequently reported included mucosal inflammation and

stomatitis (7.1%), increased alternative lengthening of telomeres (ALT) (7.1%), and increased aspartate aminotransferase (AST) (4.8%).

Only 2% of patients experienced Grade 3 hyperglycemia.

No treatment-related AEs of grade 4 or 5 severity were reported at any

1b HR+/HER2- MBC Clinical Trial Results (preliminary)

2016, Pfizer initiated a Phase 1b trial dose-finding trial with an expansion portion for safety and efficacy to evaluate gedatolisib

when added to either the standard doses of palbociclib plus letrozole or palbociclib plus fulvestrant in patients with HR+/HER2- metastatic

breast cancer.

Based on results and analyses from subsequent

clinical trials, the maximum tolerated dose was determined to be 180 mg IV once weekly.

1b HR+/HER2- ABC Clinical Trial Results

2016, Pfizer initiated a Phase 1b dose-finding trial with an expansion portion for safety and efficacy to evaluate gedatolisib when added

to either the standard doses of palbociclib plus letrozole or palbociclib plus fulvestrant in patients with HR+/HER2- advanced breast

PI3K mutation status was not used as an eligibility criterion.

Patient enrollment for the trial is complete.

total of 138 patients with HR+/HER2- metastatic breast cancer were dosed in the clinical trial.

Twelve patients from this

study continue to receive study treatment, as of December 31, 2021, ten of whom have received study treatment for more than three

total of 138 patients with HR+/HER2- advanced breast cancer were dosed in the clinical trial.

Seven patients from this study continue

to receive study treatment, as of December 31, 2022, each of whom have received study treatment for more than four years.

patients were enrolled in two dose escalation arms to evaluate the safety and tolerability and determine the MTD of gedatolisib when

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Tumors v1.0, or RECIST v1.0.

MBC with progression and no prior endocrine-based systemic therapy or a CDK4/6 inhibitor in the metastatic setting.

endocrine-based therapy for metastatic disease (CDK4/6 treatment naive).

MBC with progression during one or two prior endocrine-based systemic therapy in the metastatic setting, with no prior therapy

ABC with progression and no prior endocrine-based systemic therapy or a CDK4/6 inhibitor in the metastatic setting.

endocrine-based therapy for advanced disease (CDK4/6 treatment naive).

ABC with progression during one or two prior endocrine-based systemic therapy in the advanced setting, with no prior therapy

with any CDK inhibitor.

Second- or third-line endocrine-based therapy for metastatic disease.

MBC with progression during one or two prior endocrine-based systemic therapies in the metastatic setting and following prior

ABC with progression during one or two prior endocrine-based systemic therapies in the advanced setting and following prior

therapy with a CDK inhibitor.

Second- or third-line endocrine-based therapy for metastatic disease.

MBC having progressed on a CDK inhibitor in combination with endocrine therapy as the most recent regimen for metastatic disease.

Second- or third-line endocrine-based therapy for metastatic disease.

preliminary analysis for the 103 patients enrolled in the expansion portion of the Phase 1b clinical trial, as of the database cutoff

date of May 10, 2021, showed:

Second- or third-line endocrine-based therapy for advanced disease.

ABC having progressed on a CDK inhibitor in combination with endocrine therapy as the most recent regimen for advanced disease.

Second- or third-line endocrine-based therapy for advanced disease.

for the 103 patients enrolled in the expansion portion of the Phase 1b clinical trial, as of a database cutoff date of June 29, 2022,

analysis for all arms in aggregate:

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as a 30% reduction from the baseline tumor assessment.

safety analysis:

all arms in aggregate, all patients experienced at least one Grade 1 or Grade 2 treatment-emergent adverse event.

The most commonly

reported adverse events regardless of grade and occurring in at least 30% of patients included stomatitis (81%), neutropenia (80%),

nausea (75%), fatigue (68%), dysgeusia (46%), vomiting (45%), anemia (40%), diarrhea (34%), decreased appetite (32%), leukopenia

all arms in aggregate, the Grade 3 and 4 treatment-emergent adverse events occurring in at least 20% of patients were neutropenia

(67%), stomatitis (27%) and rash (20%).

The Grade 3 and

4 treatment-emergent adverse events occurring in at least 20% of patients were neutropenia (63%), stomatitis (27%) and rash (20%).

Neutropenia is a known class effect of CDK4/6 inhibitors.

Stomatitis was reversible in most

patients with a steroidal mouth rinse.

All grades of treatment-related adverse events related to hyperglycemia was reported in 22%

Grade 3 or 4 hyperglycemia was reported in 7% of patients.

Gedatolisib was discontinued in 10% of patients.

Stomatitis was reversible in most patients with a steroidal mouth rinse.

All grades of treatment-related adverse events related to hyperglycemia was reported in 22% of patients;

Grade 3 or 4 hyperglycemia

was reported in 7% of patients.

Gedatolisib was discontinued in less than 10% of patients.

the patients in Arm D, who received the Phase 3 dosing schedule, Grade 3 and 4 treatment-emergent adverse events occurring in at

least 20% of patients were neutropenia (67%) and stomatitis (22%).

All grades of treatment-related adverse events related

to hyperglycemia was reported in 22% of patients;

least 20% of patients were neutropenia (67%), leukopenia (22%), and stomatitis (22%).

All grades of treatment-related adverse events

related to hyperglycemia was reported in 26% of patients;

Grade 3 or 4 hyperglycemia was reported in 7% of patients.

Gedatolisib was discontinued

in 4% of patients.

best overall response and progression free survival data for each arm is presented in the table below:

was discontinued in 4% of patients.

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

Total Expansion Arms

(N=103, full analysis set)

Prior Therapy

CDKi -pretreated

CDKi- pretreated

represents PR, except in Arm A, which had 1 CR.

n (Full, response evaluable)

Study Treatment

Gedatolisib schedule

3 wks on/1 wk off

ORR 1 (evaluable)

mPFS 2 , mos (range)

PFS % at 12 mos 2

ORR represents PR, except in Arm A, which had 1 CR = complete response.

Responses per RECIST 1.1;

2 unconfirmed PR

(2) Includes 2 unconfirmed PR

Abbreviations:

CBR = clinical

benefit rate;

1L= first line, 2L= second line;

NR = not reached;

Layman 2021 SABCS

ORR, objective response rate;

PFS, progression free

Wesolowski 2022 SABCS

Gedatolisib Clinical Trials

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of at least 30% in tumor volume by RECIST v1.1.

of a data cutoff date of October 30, 2020, nine of 16 patients achieved a partial response, an ORR of 56%, and four patients had stable

Thirteen of 16 patients thus received either a partial response or stable disease, resulting in a clinical benefit rate of 81%.

of a data cutoff date of October 30, 2021, 10 of 17 patients achieved a partial response, an ORR of 59%, and four patients had stable

Fourteen of 17 patients thus received either a partial response or stable disease, resulting in a clinical benefit rate of 82%.

Best responses are shown in the following chart.

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and for partial response (>30% tumor regression).

Best Response

Patient whose target lesion decreased by 63% but a new leptomeningeal seeding occurred.

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Gedatolisib Clinical Trials

Planned Phase 3 HR+/HER2-

MBC Clinical Trial (VIKTORIA-1)

are preparing to initiate 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

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

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 651 total subjects at approximately 175 clinical sites

across the U.S., Europe, and Asia.

We expect to initiate the VIKTORIA-1 clinical trial in the first

half of 2022.

This multi-center, international trial is expected to enroll 701

total subjects at approximately 200 clinical sites across North America, Europe, Latin America, and Asia.

The first clinical site was

activated in the third quarter of 2022.

The first patient was dosed in December 2022.

clinical trial will enable separate evaluation of subjects according to their PIK3CA status.

who meet eligibility criteria and do not have confirmed PI3KCA mutations (WT) will be randomly assigned (1:1:1) to receive

who meet eligibility criteria and do not have confirmed PIK3CA mutations (WT) will be randomly assigned (1:1:1) to receive

a regimen of either gedatolisib, palbociclib, and fulvestrant (Arm A), gedatolisib and fulvestrant (Arm B), or fulvestrant (Arm C).

Up to 351 subjects who are PIK3CA WT will be enrolled.

The three-arm design will also show the contribution of gedatolisib.

Subjects who meet eligibility criteria and have confirmed PI3KCA mutations (MT) will be randomly assigned (1:1) to

receive a regimen of either gedatolisib, palbociclib, and fulvestrant (Arm D) or alpelisib and fulvestrant (Arm E).

subjects who are PIK3CA MT will be enrolled.

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).

who meet eligibility criteria and have PIK3CA mutations (MT) will be randomly assigned (3:3:1) to receive a regimen of either

gedatolisib, palbociclib, and fulvestrant (Arm D), alpelisib and fulvestrant (Arm E), or gedatolisib and fulvestrant (Arm F).

to 350 subjects who are PIK3CA MT will be enrolled.

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).

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

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Arm A or Arm B upon radiographically confirmed disease progression.

Subjects will be followed for AEs, safety laboratory testing, tumor

Subjects will be followed for AEs, safety laboratory testing, tumour

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

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probability of obtaining regulatory approval to market gedatolisib.

we plan to initiate two Phase 2 clinical trials to evaluate gedatolisib in HR+/HER2- breast cancer patients selected with a CELsignia

PI3K Pathway Test.

One trial is expected to evaluate gedatolisib in combination with fulvestrant in up to 25 patients with metastatic

breast cancer.

The second trial is expected to evaluate up to 15 patients with early-stage breast cancer with gedatolisib in combination

with palbociclib and letrozole.

These clinical trials are expected to be initiated at sites which are already participating in a trial

that is screening patients with the CELsignia HER2 Pathway Test.

Screened patients who provide a tumor biopsy will receive a CELsignia

HER2 and PI3K Test.

Patients found to have hyperactive HER2 signaling will be eligible to receive treatment with an anti-HER2 therapy

and those with hyperactive PI3K signaling will be eligible to receive gedatolisib in combination with other targeted therapies.

enrollment is expected to begin for the two trials in late 2022.

we plan to initiate a Phase 2 clinical trial to evaluate gedatolisib in combination with palbociclib and letrozole in early-stage HR+/HER2-

breast cancer patients.

The tumors from all patients will be evaluated with a CELsignia PI3K Pathway Test.

License Agreement

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 and manufacture, and commercialize gedatolisib for the treatment,

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

diagnosis and prevention of all diseases.

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are several PI3K 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.

Copiktra from Verastem, Inc., Zydelig from Gilead Sciences, Inc.

and we are aware that other companies are, or may be, developing products

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Hoffmann-La Roche Ltd, Kazia Therapeutics Limited,

Infinity Pharmaceuticals, Inc., Revolution Medicines 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.

Infinity Pharmaceuticals, Inc., Relay Therapeutics, Revolution Medicines Inc., and Takeda Pharmaceutical Company Limited.

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.

competitors may obtain FDA or other regulatory approvals for their products more rapidly than we may obtain approvals for our product

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only HER2-positive patients receive today.

We have four interventional clinical trials underway to evaluate the efficacy of HER2

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

We have three interventional clinical trials underway to evaluate the efficacy of HER2 targeted

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

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

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

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.

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.

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

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Clinical Trials

are currently collaborating on five Phase II 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 five potential new drug

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

These clinical trials

are currently collaborating on four 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 four

potential new drug indications to treat patient groups found responsive by our CELsignia test to their approved targeted therapies.

These clinical trials include:

Clinical Trial to Evaluate Efficacy of Genentech’s HER2 Targeted Therapies.

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Herceptin (trastuzumab) and Perjeta (pertuzumab), and chemotherapy in breast cancer patients selected with our CELsignia test.

on NSABP’s updated estimates of patient enrollment rates to reflect the impact of COVID-19, including the recent variants,

interim results are expected to be available in the first half of 2023 and final results approximately nine months later.

is to demonstrate that patients who have an abnormal HER2 signaling pathway, as identified by our CELsignia test, respond to treatment

with a matching targeted therapy.

goal is to demonstrate that patients who have an abnormal HER2 signaling pathway, as identified by our CELsignia test, respond to

treatment with a matching targeted therapy.

Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy.

We are collaborating with Puma Biotechnology, Inc.

and West Cancer Center to conduct a Phase II single-arm interventional trial to evaluate the efficacy and safety of Puma’s

and West Cancer Center to conduct a Phase 2 single-arm interventional trial to evaluate the efficacy and safety of Puma’s

drug, Nerlynx (neratinib), and chemotherapy in breast cancer patients selected with our CELsignia test.

Based on West Cancer Center’s

updated estimates of patient enrollment rates to reflect the impact of COVID-19, including the recent variants, interim results are

expected to be available in the first half of 2023 and final results approximately nine months later.

The goal of the trial is to

demonstrate that triple-negative breast cancer patients who have a hyperactive HER2 signaling tumor, as identified by the CELsignia

The goal of the trial is

to demonstrate that triple-negative breast cancer patients who have a hyperactive HER2 signaling tumor, as identified by the CELsignia

test, respond to treatment with Nerlynx, a matching HER2 therapy.

Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy.

In December 2020, we announced a clinical trial collaboration

with Massachusetts General Hospital and Puma, a biopharmaceutical company, to conduct a Phase II clinical trial.

This open-label

Phase II trial will evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and Faslodex (fulvestrant), an AstraZeneca

drug, in previously treated metastatic EHR-positive (HR+), HER2-negative breast cancer patients selected with our CELsignia HER2

Pathway Activity Test.

Based on Massachusetts General Hospital’s estimates of patient enrollment rates, we expect to obtain

interim results 12-15 months after the protocol is activated and final results 12 to 15 months later.

The goal of the trial is to

demonstrate that previously treated HR+, HER2-negative metastatic breast cancer patients who have hyperactive HER2 signaling

tumors, as identified by the CELsignia test, respond to treatment with Nerlynx in combination with Faslodex, a hormonal therapy that

targets the estrogen receptor.

Clinical Trial to Evaluate Efficacy of Puma’s pan-HER Inhibitor and chemotherapy.

In October 2021, we announced a clinical

trial collaboration with University of Rochester Wilmot Cancer Center and Puma, to conduct a Phase II clinical trial.

This open-label

Phase II trial will evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and the chemotherapy capecitabine,

in previously treated metastatic HER2-negative breast cancer patients with brain metastases selected with our CELsignia HER2 Pathway

Activity Test.

Based on University of Rochester Wilmot Cancer Center estimates of patient enrollment rates, we expect to obtain interim

results 12-15 months after the protocol is activated and the final results 12 to 15 months later.

We expect enrollment to begin in

the second half of 2022.

The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients

with brain metastases who have hyperactive HER2 signaling tumors, as identified by the CELsignia test, respond to treatment with

Nerlynx in combination with capecitabine.

We are collaborating with University of Rochester

Wilmot Cancer Center and Puma to evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and the chemotherapy

capecitabine, in previously treated metastatic HER2-negative breast cancer patients with brain metastases selected with our CELsignia

HER2 Pathway Activity Test.

The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer

patients with brain metastases who have hyperactive HER2 signaling tumors, as identified by the CELsignia test, respond to treatment

with Nerlynx in combination with capecitabine.

Clinical Trial to Evaluate Efficacy of Novartis’s c-Met Inhibitor and Puma’s pan-HER Inhibitor.

In March 2021, we announced

a clinical trial collaboration with MD Anderson Cancer Center, Novartis AG, and Puma, to conduct a Phase I/II clinical trial.

open-label Phase I/II trial will evaluate the efficacy and safety of Novartis’ c-Met inhibitor, Tabrecta (capmatinib), and

Puma’s pan-HER inhibitor, Nerlynx (neratinib), in previously treated metastatic HER2-negative breast cancer patients selected

with our CELsignia MP Test.

Based on MD Anderson’s estimates of patient enrollment rates, we expect to obtain interim results

12-15 months after the protocol is activated and final results 12-15 months later.

The goal of the trial is to demonstrate that previously

treated HER2-negative metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling tumors, as identified by the

CELsignia test, respond to treatment with Tabrecta in combination with Nerlynx.

We are collaborating

with MD Anderson Cancer Center, Novartis AG, and Puma, to conduct a Phase 1/2 clinical trial.

This open-label Phase 1/2 trial will

evaluate the efficacy and safety of Novartis’ c-Met inhibitor, Tabrecta (capmatinib), and Puma’s pan-HER inhibitor, Nerlynx

(neratinib), in previously treated metastatic HER2-negative breast cancer patients selected with our CELsignia MP Test.

of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients who have hyperactive HER2

and c-Met signaling tumors, as identified by the CELsignia test, respond to treatment with Tabrecta in combination with Nerlynx.

Diagnostics Industry

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Multi-Pathway Activity Test

CELsignia MP Test is a qualitative LDT that measures HER2, c-Met, and PI3K signaling activity in breast and ovarian tumor cells obtained

from patients previously diagnosed with cancer to determine whether or not the patients have one of the following cancer sub-types:

CELsignia MP Test is a qualitative laboratory developed test or LDT that measures HER2, c-Met, and PI3K signaling activity in breast

and ovarian tumor cells obtained from patients previously diagnosed with cancer to determine whether or not the patients have one of

the following cancer sub-types:

HER2 signaling driven cancer.

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of using a CELsignia test as a companion diagnostic.

intend to position our unique and highly differentiated tests as practice changing advancements in patient care.

To inform key stakeholders

of the value of our solution in order to drive adoption and reimbursement, we expect to employ the following diverse commercialization

strategies over time:

our pharmaceutical partnership and their go-to-market initiatives for the drug with which our companion diagnostic is partnered;

with oncology thought leaders, KOLs, and leading institutions on clinical research, publications, and product development;

an experienced, oncology-focused sales force in the United States and international distribution channels that are supported by dedicated

company personnel;

into the everyday practice of clinicians through our medical affairs and client services efforts;

important medical and scientific data in peer-reviewed journals and present at major industry conferences, conduct clinical trials;

with patient advocacy groups, leading cancer philanthropic organizations, and medical societies to drive awareness of CELsignia tests

and the importance of incorporating functional cellular analysis into cancer treatment.

these efforts, we will seek to promote our CELsignia test’s unique capabilities throughout the oncology community—from patients,

to the physicians treating them, to the third-party payors for these treatments and to biopharmaceutical companies developing new treatments—all

with the goal of facilitating better-informed treatment decisions for the greatest number of patients.

CELsignia test would be launched upon the approval of a pharmaceutical company’s matching drug as a companion diagnostic.

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reimbursement will be an important factor in achieving broad clinical adoption of our CELsignia tests.

At the same time, we believe broad

clinical adoption will help drive favorable reimbursement decisions.

To achieve broad reimbursement coverage with commercial third-party

payors and government payors, including Medicare and Medicaid, we plan to demonstrate the economic and clinical value of our CELsignia

tests to payors by employing a multi-pronged strategy:

At the same time, we believe

broad clinical adoption will help drive favorable reimbursement decisions.

To achieve broad reimbursement coverage with commercial

third-party payors and government payors, including Medicare and Medicaid, we plan to demonstrate the economic and clinical value of

our CELsignia tests to payors by employing a multi-pronged strategy:

a high bar for analytical validation.

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

Principal Suppliers for CELsignia

Suppliers for CELsignia

purchase commercially available reagents and instruments from a variety of suppliers.

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term extension, and relevant foreign counterparts.

respect to CELsignia, we have three issued U.S.

patents, five issued international patents, five pending U.S.

patent applications, 23

pending non-U.S.

patent applications, and one pending PCT patent application, as well as numerous corresponding non-U.S.

patent applications

covering our diagnostic approach using cell signaling analysis in living patient cells to guide treatment of patients with targeted therapies.

respect to CELsignia, we have six issued U.S.

patents and 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 patents is 2033.

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Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured.

FDA will not approve the

product unless compliance with cGMP is satisfactory and the NDA contains data that provide substantial evidence that the drug is safe

and effective in the indication studied.

The FDA will not approve

the product unless compliance with cGMP is satisfactory and the NDA contains data that provide substantial evidence that the drug is

safe and effective in the indication studied.

the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter.

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in a resubmission of the NDA, the FDA will issue an approval letter.

FDA has committed to reviewing such resubmissions in two or six

months depending on the type of information included.

The FDA has committed to reviewing such resubmissions in two to

six months depending on the type of information included.

approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

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and actions in reviewing NDA supplements as it does in reviewing NDAs.

NDA approval of a new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by FDA in any other

NDA, that drug receives five years of marketing exclusivity during which FDA cannot receive any Abbreviated New Drug Application, or

ANDA, seeking approval of a generic version of that drug.

NDA approval of a new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by the FDA in any

other NDA, that drug receives five years of marketing exclusivity during which the FDA cannot receive any Abbreviated New Drug Application,

or ANDA, seeking approval of a generic version of that drug.

Certain changes to a drug, such as the addition of a new indication to the

package insert, are associated with a three-year period of exclusivity during which FDA cannot approve an ANDA for a generic drug that

includes the change.

package insert, are associated with a three-year period of exclusivity during which the FDA cannot approve an ANDA for a generic drug

that includes the change.

An ANDA may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed.

is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before the expiration

of the exclusivity period.

If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before

the expiration of the exclusivity period.

Term Extension

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review phase—the time between NDA submission and approval up to a maximum of five years.

The time can be shortened if FDA determines

The time can be shortened if the FDA determines

that the applicant did not pursue approval with due diligence.

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preclinical and clinical research in the EU are subject to significant regulatory controls.

Clinical Trials Directive 2001/20/EC, the Directive 2005/28/EC on GCP, and the related national implementing provisions of the individual

EU Member States govern the system for the approval of clinical trials in the EU.

Under this system, an applicant must obtain prior approval

from the competent national authority of the EU Member States in which the clinical trial is to be conducted.

Furthermore, the applicant

may only start a clinical trial at a specific trial site after the competent ethics committee has issued a favorable opinion.

trial application must be accompanied by, among other documents, an IMPD, or the Common Technical Document, with supporting information

prescribed by Directive 2001/20/EC, Directive 2005/28/EC, where relevant the implementing national provisions of the individual EU Member

States and further detailed in applicable guidance documents.

All suspected unexpected serious adverse reactions to the investigated

drug that occur during the clinical trial have to be reported to the competent national authority and the Ethics Committee of the Member

State where they occurred.

April 2014, the new Clinical Trials Regulation, (EU) No 536/2014 was adopted.

Currently, the regulation is anticipated not to come into

effect before December 2021.

The Clinical Trials Regulation will be directly applicable in all the EU Member States, repealing the current

Clinical Trials Directive 2001/20/EC.

Conduct of all clinical trials performed in the EU will continue to be bound by currently applicable

provisions until the new Clinical Trials Regulation becomes applicable.

The extent to which ongoing clinical trials will be governed

by the Clinical Trials Regulation will depend on when the Clinical Trials Regulation becomes applicable and on the duration of the individual

clinical trial.

If a clinical trial continues for more than three years from the day on which the Clinical Trials Regulation becomes

applicable the Clinical Trials Regulation will at that time begin to apply to the clinical trial.

new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the EU.

The main characteristics of

the regulation include:

a streamlined application procedure via a single-entry point, the “EU portal”;

a single set of documents

to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized

procedure for the assessment of applications for clinical trials, which is divided in two parts.

Part I is assessed by the competent

authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned).

Part II is assessed separately by each Member State concerned.

Strict deadlines have been established for the assessment of clinical

trial applications.

The role of the relevant ethics committees in the assessment procedure will continue to be governed by the national

law of the concerned EU Member State.

Clinical Trials Directive 2001/20/EC, the Directive 2005/28/EC on GCP, and the related national implementing provisions of the

individual EU Member States govern the system for the approval of clinical trials in the EU.

Under this system, an applicant must

obtain prior approval from the competent national authority of the EU Member States in which the clinical trial is to be conducted.

Furthermore, the applicant may only start a clinical trial at a specific trial site after the competent ethics committee has issued

a favorable opinion.

The clinical trial application must be accompanied by, among other documents, an Investigational Medicinal

Product Dossier or IMPD, or the Common Technical Document, with supporting information prescribed by Directive 2001/20/EC, Directive

2005/28/EC, where relevant the implementing national provisions of the individual EU Member States and further detailed in

applicable guidance documents.

All suspected unexpected serious adverse reactions to the investigated drug that occur during the

clinical trial have to be reported to the competent national authority and the Ethics Committee of the Member State where they

new Clinical Trials Regulation (EU) No 536/2014 came into effect in 2022.

The Clinical Trials Regulation will be directly applicable

in all the EU Member States, repealing the current Clinical Trials Directive 2001/20/EC.

The new Clinical Trials Regulation aims to simplify

and streamline the approval of clinical trials in the EU.

The main characteristics of the regulation include:

a streamlined application

procedure via a single-entry point, the “EU portal”;

a single set of documents to be prepared and submitted for the application

as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized procedure for the assessment of applications

for clinical trials, which is divided in two parts.

Part I is assessed by the competent authorities of all EU Member States in which

an application for authorization of a clinical trial has been submitted (Member States concerned).

Part II is assessed separately by

each Member State concerned.

Strict deadlines have been established for the assessment of clinical trial applications.

The role of the

relevant ethics committees in the assessment procedure will continue to be governed by the national law of the concerned EU Member State.

However, overall related timelines will be defined by the Clinical Trials Regulation.

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and efficacy.

If these third-party payors do not consider our products to be cost-effective compared to other available products or

treatments, they may not cover our products or, if they do, the level of payment may not be sufficient to allow us to sell our products

government, state legislatures and foreign governments have shown significant interest in implementing cost-containment

programs to limit the growth of government-paid healthcare costs, including price controls and restrictions on reimbursement.

of such controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit

payments for our testing products or drugs that require use of our testing products and could adversely affect our net revenue and results.

If these third-party payors do not consider our products to be cost-effective compared to other available tests, they may

not cover our products or, if they do, the level of payment may not be sufficient to allow us to sell our products at a profit.

government, state legislatures and foreign governments have shown significant interest in implementing cost-containment programs to limit

the growth of government-paid healthcare costs, including price controls and restrictions on reimbursement.

Adoption of such controls

and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for our

testing products or drugs that require use of our testing products and could adversely affect our net revenue and results.

expect to see continued focus by Congress and the Biden Administration on regulating pricing, which could result in legislative and regulatory

changes designed to control costs.

For example, in August 2022, the IRA was signed into law, which, among other things, requires manufacturers

of certain drugs to engage in price negotiations with Medicare (beginning in 2026), imposes rebates under Medicare Part B and Medicare

Part D to penalize price increases that outpace inflation (first due in 2023), and replaces the Part D coverage gap discount program

with a new discounting program (beginning in 2025).

We continue to evaluate the impact of the IRA on our business, operations and financial

condition and results as the full effect of the IRA on our business and the pharmaceutical industry remains uncertain.

In addition, changes

to the Medicaid program or the federal 340B drug pricing program, which imposes ceilings on prices that drug manufacturers can charge

for medications sold to certain health care facilities, could have a material impact on our business.

and reimbursement schemes vary widely from country to country.

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of COVID-19 on our Business

help protect the health and safety of our employees, suppliers and collaborators, we took proactive, aggressive action from the earliest

signs of the outbreak.

We enacted rigorous safety measures in our laboratory and administrative offices, including implementing social

distancing protocols, allowing working from home for those employees that do not need to be physically present in a lab to perform their

work, suspending travel, implementing temperature checks at the entrances to our facilities, extensively and frequently disinfecting

our workspaces and providing masks to those employees who must be physically present.

We expect to continue with these measures until

the COVID-19 pandemic is better contained and we may take further actions as government authorities require or recommend or as we determine

to be in the best interests of our employees, suppliers, and collaborators.

Trials and Collaborations

a result of the COVID-19 pandemic, governmental authorities have implemented and are continuing to implement numerous and constantly

evolving measures to try to contain the virus, such as travel bans and restrictions, limits on gatherings, quarantines, shelter-in-place

orders, and business shutdowns.

As we continue to advance our clinical trial collaborations, we are in close contact with our current

clinical sponsors, and principal investigators, as well as prospective pharmaceutical company and clinical collaborators, to assess the

ongoing impact of COVID-19 on our trial enrollment timelines and collaboration discussions.

In light of the COVID-19 pandemic, the focus

of healthcare providers and hospitals on fighting the virus, and consistent with the FDA’s updated industry guidance for conducting

clinical trials issued on March 18, 2020, we are experiencing delays in the enrollment of patients in our ongoing clinical trials.

now expect interim results from the FACT-1 and FACT-2 trials to be delayed until the first half of 2023 and final results approximately

nine months later.

As the impact of COVID-19 on our industry becomes clearer, we may need to reassess the timing of our anticipated clinical

Prospective clinical trial collaborations with pharmaceutical companies and sponsors may also be delayed but the impact on

the timing of finalizing agreements is not yet known.

and Development

our facility currently remains operational, the evolving measures to try to contain the virus have impacted and may further impact our

workforce and operations, as well as those of our vendors and suppliers.

Although there is uncertainty related to the anticipated impact

of the recent COVID-19 outbreak on our future results, we believe our existing balance of cash and cash equivalents will be sufficient

to meet our cash needs arising in the ordinary course of business for at least the next twelve months.

We continue to monitor the rapidly

evolving situation and guidance from federal, state and local public health authorities and may take additional actions based on their

recommendations.

In these circumstances, there may be developments outside our control requiring us to adjust our operating plan.

a result of the COVID-19 pandemic, we experienced delays in the enrollment of patients in our ongoing FACT-1 and FACT-2 clinical trials.

While the COVID-19 pandemic has significantly subsided, future outbreaks or variants of the virus may cause additional delays in our

clinical trial work.

were organized as a Minnesota limited liability company in 2011 and commenced operations in 2012.

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of December 31, 2022, we had 45 full-time employees, most of which were engaged in research and development activities.

our employees are currently represented by a labor union or covered by a collective bargaining agreement and we believe that our relations

with our employees are good.

None of our employees

are currently represented by a labor union or covered by a collective bargaining agreement and we believe that our relations with our

employees are good.

During 2022, our voluntary turnover rate was approximately 14%.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business