What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2023-02-07 compared with 2022-02-08 · 203 added, 242 removed, 643 unchanged (41% of the section changed)

1 unchanged sentence

Our global headquarters is located in Wilmington, Delaware, where we conduct global clinical development and commercial operations.

We also conduct clinical development and commercial operations from our country offices across Europe, including our European headquarters in Morges, Switzerland, our Japanese office in Tokyo and our Canadian headquarters in Montreal.

We also conduct clinical development and commercial operations from our European headquarters in Morges, Switzerland and our other offices across Europe, as well as our Japanese office in Tokyo and our Canadian headquarters in Montreal.

As described in more detail below, we operate in two therapeutic areas that are defined by the indications of our approved medicines and the diseases for which our clinical candidates are being developed.

One therapeutic area is Hematology/Oncology, which is comprised of Myeloproliferative Neoplasms (MPNs), Graft-Versus-Host Disease (GVHD), as well as solid tumors and hematologic malignancies.

The other therapeutic area is Inflammation and Autoimmunity (IAI), which includes our newly established Dermatology commercial franchise.

One therapeutic area is Hematology/Oncology, which comprises Myeloproliferative Neoplasms (MPNs), Graft-Versus-Host Disease (GVHD), and solid tumors and hematologic malignancies.

The other therapeutic area is Inflammation and Autoimmunity (IAI), which includes our Dermatology commercial franchise.

We are also eligible to receive milestones and royalties on molecules discovered by us and licensed to third parties.

Hematology and Oncology

Our hematology and oncology franchise is comprised of four approved products, which are JAKAFI (ruxolitinib), MONJUVI (tafasitamab-cxix)/MINJUVI (tafasitamab), PEMAZYRE (pemigatinib) and ICLUSIG (ponatinib), as well as numerous clinical development programs.

Our hematology and oncology franchise comprises four approved products, which are JAKAFI (ruxolitinib), MONJUVI (tafasitamab-cxix)/MINJUVI (tafasitamab), PEMAZYRE (pemigatinib) and ICLUSIG (ponatinib), as well as numerous clinical development programs.

JAKAFI (ruxolitinib)

1 unchanged sentence

It was approved by the U.S.

Food and Drug Administration (FDA) in November 2011 for the treatment of adults with intermediate or high-risk myelofibrosis (MF), in December 2014 for the treatment of adults with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea, in May 2019 for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older and in September 2021 for the treatment of chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older .

Myelofibrosis and polycythemia vera are both myeloproliferative neoplasms (MPNs), a type of rare blood cancer, and GVHD is an adverse immune response to an allogeneic hematopoietic stem cell transplant (HSCT).

Food and Drug Administration (FDA) in November 2011 for the treatment of adults with intermediate or high-risk myelofibrosis (MF);

in December 2014 for the treatment of adults with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea;

in May 2019 for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older;

and in September 2021 for the treatment of chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older .

MF and PV are both myeloproliferative neoplasms (MPNs), a type of rare blood cancer, and GVHD is an adverse immune response to an allogeneic hematopoietic stem cell transplant (HSCT).

Under our collaboration agreement with our collaboration partner Novartis Pharmaceutical International Ltd., Novartis received exclusive development and commercialization rights to ruxolitinib outside of the United States for all hematologic and oncologic indications and sells ruxolitinib outside of the United States under the name JAKAVI.

65 unchanged sentences

The most common hematologic adverse reactions (incidence > 35%) were anemia and thrombocytopenia.

The most common nonhematologic adverse reactions (incidence ≥ 20%) were infections (pathogen not specified) and viral infection.

The most common non-hematologic adverse reactions (incidence ≥ 20%) were infections (pathogen not specified) and viral infection.

In addition, the FDA updated labeling for JAKAFI to include warnings of increased risk of major adverse cardiovascular events, thrombosis, and secondary malignancies related to another JAK-inhibitor treating rheumatoid arthritis, a condition for which JAKAFI is not indicated.

1 unchanged sentence

We have retained all development and commercialization rights to JAKAFI in the United States and are eligible to receive development and sales milestones as well as royalties from product sales outside the United States.

We hold patents that cover the composition of matter and use of ruxolitinib, which patents, including applicable extensions, expire in mid-2028.

We hold patents that cover the composition of matter and use of ruxolitinib.

These patents, including applicable extensions, currently expire in late-2028.

We have been granted pediatric exclusivity which adds six months to the expiration for all ruxolitinib patents presently listed in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

MONJUVI (tafasitamab-cxix) / MINJUVI (tafasitamab)

26 unchanged sentences

PEMAZYRE is the first FDA-approved treatment for this indication, which was approved under accelerated approval based on overall response rate and duration of response (DOR).

In March 2021, PEMAZYRE was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with unresectable biliary tract cancer (BTC) with an FGFR2 fusion gene, worsening after

cancer chemotherapy.

Also in March 2021, PEMAZYRE was approved by the European Commission (EC) for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

7 unchanged sentences

FIGHT-302, a Phase III trial of pemigatinib for the first-line treatment of patients with cholangiocarcinoma and FGFR2 fusions or rearrangements, is ongoing.

We have retained all rights to PEMAZYRE globally, other than those granted to Innovent Biologics, Inc.

to develop and commercialize pemigatinib in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.

In March 2022, PEMAZYRE was approved by the National Medical Products Administration (NMPA) of the People ’ s Republic of China for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth receptor 2 (FGFR2) fusion or rearrangement as confirmed by a validated diagnostic test that have progressed after at least one prior line of systemic therapy.

In August 2022, PEMAZYRE was approved by the FDA as the first and only targeted treatment for myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

MLNs with FGFR1 rearrangement are extremely rare and aggressive blood cancers.

ICLUSIG (ponatinib)

9 unchanged sentences

Clinical Programs in Hematology and Oncology

Ruxolitinib and itacitinib

As part of our ongoing LIMBER (Leadership In MPNs BEyond Ruxolitinib) clinical development initiative, which is designed to improve and expand therapeutic options for patients with myeloproliferative neoplasms, we are evaluating combinations of ruxolitinib with other therapeutic modalities, as well as developing a once-a-day formulation of ruxolitinib for potential use as monotherapy and combination therapy.

Bioavailability and bioequivalence data were published for ruxolitinib’s once-daily (QD) extended release (XR) formulation at the European Hematology Association (EHA) 2021 Virtual Congress in June 2021.

The FDA accepted the New Drug Application (NDA) for QD ruxolitinib with a Prescription Drug User Fee Act (PDUFA) target action date of March 23, 2023.

Based on positive Phase II data, we opened two pivotal trials of ruxolitinib in combination with parsaclisib (PI3Kδ) in first-line MF (LIMBER-313) and in MF patients with a suboptimal response to ruxolitinib monotherapy (LIMBER-304), and both trials are ongoing.

Additional Phase II trials combining ruxolitinib with investigational agents from our portfolio such as INCB57643 (BET) and INCB00928 (ALK2) in patients with MF are in preparation, and additional discovery and development initiatives are also ongoing within the LIMBER program, which are evaluating both internally-discovered compounds, including itacitinib (JAK1), and candidates from collaboration partners.

Itacitinib is a selective JAK1 inhibitor being evaluated in GRAVITAS-309, a Phase II/III trial of itacitinib in patients with steroid-naïve chronic GVHD.

The FDA has granted itacitinib orphan drug status for GVHD.

Additional Phase II trials combining ruxolitinib with investigational agents from our portfolio such as INCB57643 (BET) and INCB00928 (ALK2) in patients with MF are ongoing, and additional discovery and development initiatives are also ongoing within the LIMBER program, which are evaluating internally-discovered compounds, and candidates from collaboration partners.

In September 2021, we and Syndax Pharmaceuticals, Inc.

3 unchanged sentences

A 68% overall response rate and broad clinical benefit across multiple organs were observed at doses being assessed in AGAVE-201, a global pivotal trial evaluating axatilimab monotherapy in patients with chronic GVHD in the third line setting.

Additional trials of axatilimab are planned in patients with chronic GVHD, including a Phase II trial in combination with a JAK inhibitor in patients with steroid-refractory cGVHD.

Additional trials of axatilimab are planned in patients with chronic GVHD, including a Phase II trial in combination with ruxolitinib in patients with newly-diagnosed cGVHD.

In May 2022, Syndax announced that axatilimab was granted fast-track designation by the FDA for the treatment of patients with chronic GVHD after failure of two or more lines of systemic therapy.

Tafasitamab is an anti-CD19 antibody and is being investigated as a therapeutic option in B cell malignancies in a number of ongoing and planned combination trials.

1 unchanged sentence

firstMIND is a Phase Ib safety trial of tafasitamab as a first-line therapy for patients with DLBCL, and frontMIND, a placebo-controlled Phase III trial evaluating tafasitamab in combination with lenalidomide added to rituximab plus chemotherapy (R-CHOP) as a first-line therapy for patients with DLBCL, is ongoing.

A placebo-controlled Phase III trial (inMIND) of tafasitamab added to lenalidomide plus rituximab (R 2 ) in patients with relapsed or refractory follicular or marginal zone lymphomas is ongoing, as is a proof-of-concept study (topMIND) evaluating tafasitamab in combination with parsaclisib (PI3Kδ) in patients with relapsed or refractory B-cell malignancies.

We are also preparing to initiate a proof-of-concept study of tafasitamab, lenalidomide and plamotamab in patients with r/r DLBCL.

A placebo-controlled Phase III trial (inMIND) of tafasitamab added to lenalidomide plus rituximab (R 2 ) in patients with relapsed or refractory follicular or marginal zone lymphomas is ongoing.

A proof-of-concept study of tafasitamab, lenalidomide and plamotamab in patients with r/r DLBCL is also ongoing.

In January 2021, the FDA granted orphan drug designation to tafasitamab as a treatment for patients with follicular lymphoma.

3 unchanged sentences

The program initially included three Phase II trials – FIGHT-201 in patients with bladder cancer, FIGHT-202 in patients with cholangiocarcinoma, and FIGHT-203 in patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement.

Based on data generated from these ongoing trials, we have initiated additional trials.

Based on data generated from these trials, we have initiated additional trials including FIGHT-302, a Phase III study in first-line cholangiocarcinoma.

FIGHT-207, a solid tumor-agnostic trial evaluating pemigatinib in patients with driver-alterations of FGF/FGFR, is now closed to recruitment.

Based on findings from this study, we have identified populations that may potentially benefit from treatment with pemigatinib and intend to initiate Phase II studies in glioblastoma and non-small cell lung cancer.

Based on findings from this study, we have identified populations that may potentially benefit from treatment with pemigatinib and have initiated two Phase II trials – FIGHT-209 in patients with glioblastoma and FIGHT-210 in patients with non-small cell lung cancer.

Pemigatinib has Breakthrough Therapy designation as a treatment for patients with myeloid/lymphoid neoplasms (MLN) with FGFR1 rearrangement who have relapsed or are refractory to initial chemotherapy.

5 unchanged sentences

Results from four cohorts were presented at the American Society of Hematology (ASH), including in r/r follicular lymphoma (CITADEL-203), in BTK-naïve r/r marginal zone lymphoma (CITADEL-204) and in both BTK-naïve and BTK-experienced r/r mantle cell lymphoma (CITADEL-205).

In October 2021, we announced the FDA acceptance of a NDA seeking approval of parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma.

The submission was based on data from several Phase 2 studies (CITADEL-203, -204 and -205) evaluating parsaclisib as a treatment for relapsed or refractory NHLs (follicular, marginal zone and mantle cell).

In January 2022, we announced that we withdrew the NDA seeking approval of parsaclisib for the three indications in NHL.

In October 2021, we announced the FDA acceptance of an NDA seeking approval of parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma.

The submission was based on data from several Phase II studies (CITADEL-203, -204 and -205) evaluating parsaclisib as a treatment for relapsed or refractory non-Hodgkin lymphomas (follicular, marginal zone and mantle cell).

In January 2022, we announced that we withdrew the NDA seeking approval of parsaclisib for the three indications in non-Hodgkin lymphoma.

The decision to withdraw the NDA followed discussions with FDA regarding confirmatory studies that we determined cannot be completed within a reasonable time period to support an accelerated approval.

We have an ongoing EMA submission under review for MZL.

A Phase II trial of parsaclisib in patients with autoimmune hemolytic anemia (AIHA), a rare red blood cell disorder, is ongoing.

In June 2021, data from the Phase II trial were presented at EHA.

In July 2022, we withdrew the Marketing Authorization Application (MAA) seeking approval of parsaclisib in marginal zone lymphoma following discussions with the European Medicines Agency (EMA) regarding the confirmatory study needed to support the approval which we determined were not feasible.

Parsaclisib is being evaluated as a treatment for autoimmune hemolytic anemia (AIHA), a rare red blood cell disorder.

In June 2021, data from a Phase II trial were presented at EHA.

The majority of patients achieved a response with parsaclisib over the initial 12-week treatment period and treatment with parsaclisib was generally well tolerated.

Based on these results, we initiated a Phase III trial in warm AIHA.

Based on these results, we initiated a Phase III trial (PATHWAY) in warm AIHA.

The FDA has granted orphan drug designation to parsaclisib as a treatment for patients with AIHA.

4 unchanged sentences

Potentially registration-enabling trials in microsatellite instability-high (MSI-H) endometrial cancer and Merkel cell carcinoma are ongoing.

The Phase III POD1UM-303 trial of retifanlimab in combination with platinum-based chemotherapy as a first-line treatment for patients with SCAC is underway.

In July 2021, we announced that the FDA issued a complete response letter (CRL) for the BLA of retifanlimab for the treatment of squamous cell carcinoma of the anal canal (SCAC).

In October 2021, we announced that we withdrew the Marketing Authorization Application (MAA) seeking approval of retifanlimab in SCAC.

The Phase III POD1UM-304 trial is evaluating retifanlimab in combination with platinum-based chemotherapy as a first-line treatment for patients with non-small cell lung cancer (NSCLC), and in October 2020, our collaboration partner Zai Lab announced dosing of the first patient in China.

The Phase III POD1UM-303 trial of retifanlimab in combination with platinum-based chemotherapy as a first-line treatment for patients with squamous cell carcinoma of the anal canal (SCAC) is underway.

In July 2021, we announced that the FDA issued a complete response letter (CRL) for the BLA of retifanlimab for the treatment of SCAC.

In October 2021, we announced that we withdrew the MAA seeking approval of retifanlimab in SCAC.

The Phase III POD1UM-304 trial is evaluating retifanlimab in combination with platinum-based chemotherapy as a first-line treatment for patients with non-small cell lung cancer (NSCLC).

Retifanlimab has been granted Fast Track designation for the treatment of certain patients with advanced or metastatic MSI-H or DNA mismatch repair (dMMR) endometrial cancer, for the treatment of certain patients with locally advanced or metastatic SCAC and for the treatment of Merkel cell carcinoma (MCC).

The FDA and EMA have granted orphan drug designation to retifanlimab as a treatment for patients with locally advanced or metastatic SCAC and the FDA has granted orphan drug designation to retifanlimab as a treatment for patients with MCC.

In November 2021, we highlighted Phase I clinical safety and efficacy data for our oral PD-L1 program which included two compounds, INCB99280 and INCB99318.

Tumor shrinkage was observed for both oral PD-L1 inhibitors and both were generally well tolerated.

We plan to evaluate INCB99280 in Phase II as monotherapy and in combination with other antitumor agents.

Further dose escalation and dose expansion trials are ongoing with INCB99318.

In November 2022, (i) updated safety and preliminary efficacy data for INCB99280 and INCB99318 was presented at the Society for Immunotherapy of Cancer, and (ii) we and Mirati Therapeutics, Inc.

announced a clinical trial collaboration and supply agreement to investigate the combination of INCB99280 and adagrasib, a KRASG12C selective inhibitor, in patients with KRASG12C-mutated solid tumors.

Indication and status

Once-a-day ruxolitinib (JAK1/JAK2)

Myelofibrosis, polycythemia vera and GVHD:

clinical pharmacology studies

ruxolitinib + parsaclisib

(JAK1/JAK2 + PI3Kδ)

ruxolitinib XR (QD) (JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD:

NDA under review

ruxolitinib + parsaclisib (JAK1/JAK2 + PI3Kδ)

Myelofibrosis:

2 unchanged sentences

Phase III (suboptimal responders to ruxolitinib) (LIMBER-304)

ruxolitinib + INCB57643

(JAK1/JAK2 + BET)

ruxolitinib + INCB57643 (JAK1/JAK2 + BET)

Myelofibrosis:

Phase II in preparation

ruxolitinib + INCB00928

(JAK1/JAK2 + ALK2)

ruxolitinib + zilurgisertib (JAK1/JAK2 + ALK2)

Myelofibrosis:

Phase II in preparation

ruxolitinib + CK0804 1

(JAK1/JAK2 + CB-Tregs)

ruxolitinib + CK0804 1 (JAK1/JAK2 + CB-Tregs)

Myelofibrosis:

PoC in preparation

itacitinib (JAK1)

Treatment-naïve chronic GVHD:

Phase II/III (GRAVITAS-309)

Phase I (LIMBER-TREG108)

ruxolitinib + axatilimab (JAK1/JAK2 + anti-CSF-1R) Chronic GVHD (newly diagnosed):

Phase I/II in preparation

axatilimab (anti-CSF-1R) 2

7 unchanged sentences

Phase III (inMIND)

r/r B-cell malignancies:

PoC with parsaclisib (PI3Kδ) (topMIND)

r/r B-cell malignancies:

PoC with lenalidomide and plamotamab in preparation 4

pemigatinib (FGFR1/2/3)

Phase III (FIGHT-302)

Myeloid/lymphoid neoplasms (MLN):

pemigatinib (FGFR1/2/3) Myeloid/lymphoid neoplasms (MLN):

Phase II (FIGHT-203);

approved by FDA

Phase III (FIGHT-302)

Glioblastoma:

Phase II in preparation

parsaclisib (PI3Kδ)

Autoimmune hemolytic anemia:

Phase II (FIGHT-209)

Phase II (FIGHT-210)

parsaclisib (PI3Kδ) Warm autoimmune hemolytic anemia:

Phase III (PATHWAY)

6 unchanged sentences

Phase III (POD1UM-304)

INCB99280 (Oral PD-L1) Solid tumors:

KRASG12C-mutated solid tumors:

Phase I/Ib in combination with adagrasib, in preparation

INCB99318 (Oral PD-L1)

Solid tumors:

Development collaboration with Cellenkos, Inc.

1 unchanged sentence

tafasitamab development in collaboration with MorphoSys.

Clinical collaboration with MorphoSys and Xencor, Inc.

to investigate the combination of tafasitamab plus lenalidomide in combination with Xencor’s CD20xCD3 XmAb bispecific antibody, plamotamab.

retifanlimab licensed from MacroGenics.

Earlier-Stage Development Programs in Hematology and Oncology

We also have a number of other earlier-stage clinical programs in hematology and oncology, as detailed in the table below.

INCB123667 (CDK2)

In the cell cycle, the serine threonine kinase, CDK2, regulates the transition from the G1 phase (cell growth) to the S-phase (DNA replication).

INCB123667 is a novel, potent and selective oral small molecule inhibitor of CDK2 which has been shown to suppress tumor growth as monotherapy and in combination with standard of care, in Cyclin E amplified tumor models, in vivo.

In July 2022, we initiated a Phase I dose-escalation and dose-expansion study evaluating INCB123667 in adults with selected advanced or metastatic solid tumors.

INCA32459 (LAG-3xPD-1)

In collaboration with Merus N.V.

we have developed INCA32459, a novel LAG3xPD-1 bispecific antibody that is currently being evaluated in clinical studies.

INCA33989 (mCALR)

In December 2022, new research detailing the development and mechanism of action of INCA033989, an Incyte-discovered, investigational novel anti-mutant calreticulin (CALR)-targeted monoclonal antibody, was featured in the Plenary Scientific Session at the 64th American Society of Hematology (ASH) Annual Meeting.

INCA033989 binds with high affinity to mutant CALR and inhibits oncogenesis, the process of cells becoming cancerous, in cells expressing this oncoprotein.

CALR mutations are responsible for disease development in approximately 25-35% of patients with MF and ET.

INCA33989 is currently expected to enter clinical studies in 2023.

Our earlier-stage clinical programs in hematology and oncology, are included in the table below.

We intend to describe these programs more fully if we obtain clinical proof-of-concept and establish that a program warrants further development in a specific indication or group of indications.

Small molecules

INCB81776 (AXL/MER), epacadostat (IDO1), INCB86550 (PD-L1), INCB99280 (PD-L1), INCB99318 (PD-L1), INCB106385 (A2A/A 2B )

Monoclonal antibodies 1

INCAGN1876 (GITR), INCAGN2385 (LAG-3), INCAGN1949 (OX40), INCAGN2390 (TIM-3), INCA00186 (CD73)

Modality Candidates

Small molecules INCB81776 (AXL/MER), INCB106385 (A2A/A2B), INCB123667 (CDK2)

Monoclonal antibodies INCAGN1876 (GITR) 1 , INCAGN2385 (LAG-3) 1 , INCAGN2390 (TIM-3) 1 , INCA00186 (CD73), INCA33989 (mCALR)

Bispecific antibodies INCA32459 (LAG-3xPD-1) 2

Discovery collaboration with Agenus Inc.

Development collaboration with Merus

Inflammation and AutoImmunity (IAI)

2 unchanged sentences

OPZELURA (ruxolitinib) cream

Atopic Dermatitis .

In September 2021, we announced that the FDA approved OPZELURA (ruxolitinib) cream, a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

9 unchanged sentences

The most common (≥1%) treatment-emergent adverse reactions in patients treated with OPZELURA were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increased, urticaria, folliculitis, tonsillitis and rhinorrhea.

Clinical Programs in Dermatology

Ruxolitinib cream is a potent, selective inhibitor of JAK1 and JAK2 that provides the opportunity to directly target diverse pathogenic pathways that underlie certain dermatologic conditions, including atopic dermatitis, vitiligo and chronic hand eczema.

We are currently evaluating ruxolitinib cream in a Phase III trial, TRuE-AD3, in pediatric atopic dermatitis patients ages ≥2 years to < 12 years.

A Phase III trial evaluating ruxolitinib cream in chronic hand eczema is in preparation.

In May 2021, we announced positive topline results from the Phase III TRuE-V program evaluating ruxolitinib cream as a treatment for adolescent and adult patients with vitiligo.

Both TRuE-V1 and TRuE-V2 studies met the primary and key secondary endpoints, including patient reported outcomes.

The overall efficacy and safety profile of ruxolitinib cream was consistent with previously reported Phase II data, and no new safety signals were observed.

In October 2021, data from the Week 24 analysis of the Phase III TRuE-V program were presented at the European Academy of Dermatology and Venereology Congress (EADV).

In July 2022, we announced that the FDA approved OPZELURA for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.

OPZELURA was approved for continuous use and no limits to duration as a treatment for nonsegmental vitiligo.

Vitiligo is a chronic autoimmune depigmenting skin disease characterized by patches of the skin losing their pigment.

It is estimated that there are at least 1.5 million patients diagnosed with vitiligo in the United States, with the majority of patients (approximately 85%) suffering from nonsegmental vitiligo.

OPZELURA is the first and only FDA approved treatment for repigmentation of vitiligo lesions.

The approval of OPZELURA in vitiligo was based on two randomized, double-blind, vehicle-controlled Phase III studies (TRuE-V1 and TRuE-V2) evaluating the safety and efficacy of OPZELURA in adolescents and adults with nonsegmental vitiligo.

Treatment with 1.5% ruxolitinib cream twice daily (BID) resulted in greater improvement versus vehicle for the primary and all key secondary endpoints in both the TRuE-V1 and TRuE-V2 studies.

Results, which were consistent across both studies, showed that 29.9% of patients applying ruxolitinib cream achieved ≥75% improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75), the primary endpoint.

The overall safety profile of ruxolitinib cream in vitiligo was consistent with previous study data.

In the TRuE-V studies, patients using ruxolitinib cream did not report clinically significant application site reactions.

Treatment-emergent adverse events were consistent with previous studies, with no serious treatment-related adverse events reported.

In October 2021, we announced the validation of the European Marketing Authorization Application (MAA) for ruxolitinib cream as a potential treatment for adolescents and adults (age ≥12 years) with non-segmental vitiligo with facial involvement.

In December 2021, we announced that the U.S.

FDA accepted for Priority Review the sNDA for ruxolitinib cream as a potential treatment for adolescents and adults (age ≥ 12 years) with vitiligo.

The Prescription Drug User Fee Act (PDUFA) target action date is April 18, 2022.

Vitiligo is a long-term skin condition characterized by patches of the skin losing their pigment.

It is estimated that vitiligo affects 0.5-2% of the US population and, therefore, there are at least 1.5 million patients in the United States with this disorder.

There are no FDA approved treatments for repigmentation of vitiligo lesions.

We are also developing INCB54707, which is an oral small molecule selective JAK1 inhibitor.

INCB54707 is undergoing evaluation in patients with hidradenitis suppurativa (HS), a chronic skin condition where lesions develop as a result of inflammation and infection of the sweat glands.

In October 2020, initial results from the clinical program were presented and a randomized Phase IIb trial of INCB54707 is underway in patients with HS.

In March 2021, we initiated a Phase II trial evaluating INCB54707 in patients with vitiligo.

A Phase II trial evaluating INCB54707 in patients with prurigo nodularis is ongoing.

Results, which were consistent across both studies, showed that 29.9% of patients applying ruxolitinib cream achieved >75% improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75) at Week 24, the primary endpoint.

At Week 52, approximately 50% of patients achieved F-VASI75.

The most common (>1%) treatment-emergent adverse reactions in patients treated with OPZELURA were application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema and pyrexia.

Clinical Programs in Dermatology

Ruxolitinib cream

In October 2021, we announced the validation of the MAA for ruxolitinib cream as a potential treatment for adolescents and adults (age ≥12 years) with nonsegmental vitiligo with facial involvement.

In November 2022, we initiated two Phase II trials evaluating ruxolitinib cream in lichen planus and lichen sclerosus.

Lichen planus is a recurrent inflammatory condition affecting the skin and mucosal surfaces and can result in itchy, purple bumps on the skin.

Lichen sclerosus is a chronic inflammatory skin disease most commonly affecting women and can result in painful ulcers and intense itching.

In December 2022, we also initiated a Phase II trial evaluating ruxolitinib cream in mild to moderate hidradenitis suppurativa.

We are also developing povorcitinib (formerly INCB54707), which is an oral small molecule selective JAK1 inhibitor.

Povorcitinib is undergoing evaluation in patients with hidradenitis suppurativa (HS), a chronic skin condition where lesions develop as a result of inflammation and infection of the sweat glands.

In October 2020, initial results from the clinical program were presented and a randomized Phase IIb trial of povorcitinib is underway in patients with HS.

In March 2021, we initiated a Phase II trial evaluating povorcitinib in patients with vitiligo.

A Phase II trial evaluating povorcitinib in patients with prurigo nodularis is ongoing.

In August 2022, we presented results from the Phase II trial of povorcitinib in HS.

In December 2022, we initiated two Phase III trials (STOP-HS1 and STOP-HS2) in moderate to severe hidradenitis suppurativa.

Earlier-Stage Development Programs in Dermatology

In November 2022, we acquired Villaris Therapeutics, Inc., an asset-centric biopharmaceutical company focused on the development of novel antibody therapeutics for vitiligo.

Its lead asset, auremolimab (VM6) is a novel, humanized anti-IL-15Rβ monoclonal antibody designed to target and deplete autoreactive resident memory T cells (TRM) that has demonstrated efficacy as a treatment for vitiligo in preclinical models.

IND-enabling studies are underway, and clinical development for auremolimab is currently expected to begin in 2023.

Indication and status

2 unchanged sentences

Phase III pediatric study (TRuE-AD3)

Chronic hand eczema:

Phase III in preparation

Phase III (TRuE-V1, TRuE-V2);

primary endpoint met in both studies);

sNDA under Priority Review and MAA under review

INCB54707 (JAK1)

approved by FDA;

MAA under review

Lichen planus:

Lichen sclerosus:

Hidradenitis suppurativa:

ruxolitinib cream + NB-UVB (JAK1/JAK2 + phototherapy) Vitiligo:

(JAK1) Hidradenitis suppurativa:

Phase III (STOP-HS1, STOP-HS2)

Prurigo nodularis:

(anti-IL-15Rβ) Vitiligo:

Phase I in preparation

Novartis’ rights for ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.

Clinical Programs in Other IAI

A Phase II trial of INCB00928 is in preparation for patients with fibrodysplasia ossificans progressiva (FOP), a disorder in which muscle tissue and connective tissue are gradually replaced by bone.

In May 2022, we initiated a Phase II trial evaluating INCB00928 in patients with fibrodysplasia ossificans progressiva (FOP), a disorder in which muscle tissue and connective tissue are gradually replaced by bone.

The FDA has granted Fast Track designation and orphan drug designation to INCB00928 as a treatment for patients with FOP.

Indication and status

INCB00928 (ALK2)

Fibrodysplasia ossificans progressiva:

Phase II in preparation

INCB00928 (ALK2) Fibrodysplasia ossificans progressiva:

Collaborative Partnered Programs

15 unchanged sentences

In February 2017, we and Lilly announced that the European Commission approved baricitinib as OLUMIANT for the treatment of moderate-to-severe rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs).

In July 2017, the Japanese Ministry of Health, Labour and Welfare (MHLW) granted marketing approval for OLUMIANT for the treatment of rheumatoid arthritis (including the prevention of structural injury of joints) in patients with inadequate response to standard-of-care therapies.

In July 2017, the MHLW granted marketing approval for OLUMIANT for the treatment of rheumatoid arthritis (including the prevention of structural injury of joints) in patients with inadequate response to standard-of-care therapies.

In June 2018, the FDA approved the 2mg dose of OLUMIANT for the treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) inhibitor therapies.

5 unchanged sentences

In January 2020, we and Lilly announced that baricitinib met the primary endpoint in both BREEZE-AD4 and BREEZE-AD5, the results of which completed the placebo-controlled data program intended to support global registrations.

An sNDA for baricitinib has been submitted by

Lilly for the treatment of patients with moderate to severe AD.

A supplemental New Drug Application (sNDA) for baricitinib was submitted by Lilly for the treatment of patients with moderate to severe AD.

In April 2021, we and Lilly announced the FDA extended the review period for the sNDA for baricitinib for the treatment of moderate to severe AD by three months to allow time for additional data analyses.

5 unchanged sentences

In December 2020, baricitinib was approved by the MHLW for the treatment of patients with moderate-to-severe AD.

Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation.

In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the tissue lining the lungs and heart, and the brain.

Lilly has conducted a Phase II trial to evaluate the safety and efficacy of baricitinib in patients with SLE.

Baricitinib’s activity profile suggests that it inhibits cytokines implicated in SLE such as type I interferon (IFN), type II IFN-γ, IL-6, and IL-23 as well as other cytokines that may have a role in SLE, including granulocyte macrophage colony stimulating factor (GM-CSF) and IL-12.

In January 2022, Lilly announced the discontinuation of the Phase III development program for baricitinib in SLE based on top-line efficacy results from two pivotal Phase III trials (SLE-BRAVE-I and –II).

The primary endpoint of SRI-4 response was reached in SLE-BRAVE-I but was not reached in SLE-BRAVE-II and key secondary endpoints were not met in either study.

Alopecia Areata .

5 unchanged sentences

The two studies showed statistically significant improvement in scalp hair regrowth across both baricitinib dosing groups when compared to placebo.

Regulatory applications for baricitinib as a treatment for alopecia areata have been submitted in the U.S., Europe and Japan.

In March 2022, we and Lilly announced positive 52 week results from BRAVE-AA1 and BRAVE-AA2 at the American Academy of Dermatology (AAD) annual meeting showing 40% of adults saw at least 80% scalp coverage.

In June 2022, the FDA approved 2mg, and 4mg doses of OLUMIANT for the treatment of adults with severe alopecia areata, becoming the first and only systemic treatment in the indication.

In June 2022, OLUMIANT was approved as a treatment for alopecia areata in Europe and Japan.

Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation.

In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the tissue lining the lungs and heart, and the brain.

Lilly has conducted a Phase II trial to evaluate the safety and efficacy of baricitinib in patients with SLE.

The primary endpoint of SRI-4 response was reached in SLE-BRAVE-I but was not reached in SLE-BRAVE-II and key secondary endpoints were not met in either study.

In May 2020, we amended our agreement with Lilly to enable Lilly to commercialize baricitinib for the treatment of COVID-19.

3 unchanged sentences

The EUA now provides for the use of baricitinib for treatment of COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

In June 2022, we and Lilly announced the FDA approved baricitinib as OLUMIANT for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or ECMO.

Capmatinib is a potent and highly selective MET inhibitor.

1 unchanged sentence

Under our agreement, Novartis received worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Capmatinib is being evaluated

in patients with hepatocellular carcinoma, non-small cell lung cancer and other solid tumors, and may have potential utility as a combination agent.

Capmatinib is being evaluated in patients with hepatocellular carcinoma, non-small cell lung cancer and other solid tumors, and may have potential utility as a combination agent.

MET is a clinically validated receptor kinase cancer target.

10 unchanged sentences

In June 2020, we and Novartis announced that the MHLW approved TABRECTA for METex14 mutation-positive advanced and/or recurrent unresectable NSCLC.

In April 2022, we and Novartis announced a positive opinion from the CHMP based on data from the Phase II GEOMETRY mono-1 study showing an overall response rate (ORR) of 51.6% in a cohort evaluating second-line patients only and 44% in all previously-treated patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to MET exon 14 skipping.

In June 2022, we and Novartis announced the European Commission approval of capmatinib as TABRECTA as monotherapy treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year globally.

1 unchanged sentence

Though rare, this mutation is an indicator of especially poor prognosis and poor responses to standard therapies, including immunotherapy.

Graft-versus-host disease.

In March 2022, we and Novartis announced a positive opinion from the CHMP for ruxolitinib in acute and chronic GVHD, based on data from the Phase III REACH2 and REACH3 trials.

GVHD is a life-threatening complication of stem cell transplants, with no established standard of care in Europe for patients who do not adequately respond to first-line steroid treatment.

In May 2022, we and Novartis announced the EC approval of ruxolitinib as JAKAVI for the treatment of acute or chronic GVHD in patients aged 12 years and older who have inadequate response to corticosteroids or other systemic therapies.

Indication and status

1 unchanged sentence

Atopic dermatitis:

Phase III (BREEZE-AD);

approved in European Union and Japan

approved in Europe and Japan

Severe alopecia areata:

Phase III (BRAVE-AA1, BRAVE-AA2);

submissions in U.S., EU, and Japan

approved in the United States, Europe and Japan

capmatinib (MET) 2

NSCLC (with MET exon 14 skipping mutations):

approved in United States and Japan;

MAA under review

approved in the United States, Europe and Japan

ruxolitinib (JAK1/JAK2) 3

Acute and chronic GVHD:

MAA and J-NDA under review

approved in Europe;

J-NDA under review

baricitinib licensed to Lilly.

4 unchanged sentences

We also evaluate opportunities for acquiring products or rights to products and technologies that are complementary to our business from other companies and medical research institutions.

Below is a brief description of our significant business relationships and collaborations and related license agreements that expand our pipeline and provide us with certain rights to existing and potential new products and

technologies.

Additional information regarding our collaboration agreements, including their financial and accounting impact on our business and results of operations, can be found in Note 7 of notes to the consolidated financial statements included in Item 8 of this report.

11 unchanged sentences

In December 2018, we entered into a Research Collaboration and Licensing Agreement with Innovent Biologics, Inc.

Under the terms of this agreement, Innovent received exclusive development and commercialization rights to pemigatinib and our clinical-stage product candidates itacitinib and parsaclisib in hematology and oncology indications in mainland China, Hong Kong, Macau and Taiwan.

In July 2019, we entered into a Collaboration and License Agreement with a subsidiary of Zai Lab Limited.

Under the terms of this agreement, Zai Lab’s subsidiary received development and exclusive commercialization rights to retifanlimab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.

We retained an option to assist in the promotion of retifanlimab in Zai Lab’s licensed territories.

Under the terms of this agreement, Innovent received exclusive development and commercialization rights to pemigatinib and our clinical-stage product candidate parsaclisib in hematology and oncology indications in mainland China, Hong Kong, Macau and Taiwan.

In August 2021, we entered into a Collaboration and License Agreement with a subsidiary of InnoCare Pharma Limited.

Under the terms of this agreement, InnoCare’s subsidiary received development and exclusive commercialization rights to tafasitamab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.

In April 2022, we entered into a Strategic Alliance Agreement with Maruho Co., Ltd.

Under the terms of this agreement, Maruho received development, manufacturing and exclusive commercialization rights to ruxolitinib cream, and other potential future topical formulations of ruxolitinib, in autoimmune and inflammatory dermatologic diseases in Japan.

CMS Aesthetics Limited

In December 2022, we entered into a Collaboration and License Agreement with CMS Aesthetics Limited, a subsidiary of China Medical System Holdings Limited.

Under the terms of the agreement, CMS received an exclusive license to develop and commercialize, and a non-exclusive license to manufacture, ruxolitinib cream, and potentially other future topical formulations of ruxolitinib, in autoimmune and inflammatory dermatologic diseases, including vitiligo and atopic dermatitis, for patients in mainland China, Hong Kong, Macau, Taiwan and Southeast Asia.

In-License Agreements

1 unchanged sentence

and its wholly-owned subsidiary, 4-Antibody AG (now known as Agenus Switzerland Inc.), which we collectively refer to as Agenus.

Under this agreement, the parties have agreed to collaborate on the discovery of novel immuno-therapeutics

using Agenus’ antibody discovery platforms.

Under the terms of this agreement, as amended in February 2017, we received exclusive worldwide development and commercialization rights to four checkpoint modulators directed against GITR, OX40, LAG-3 and TIM-3.

In addition to the initial four program targets, we and Agenus have the option to jointly nominate and pursue additional targets within the framework of the collaboration, and in November 2015, three more targets were added, two of which were removed from the collaboration under the February 2017 amendments.

Takeda (ARIAD)

In June 2016, we acquired from ARIAD Pharmaceuticals, Inc.

all of the outstanding shares of ARIAD Pharmaceuticals (Luxembourg) S.à.r.l., the parent company of ARIAD’s European subsidiaries responsible for the development and commercialization of ICLUSIG in the European Union and other countries.

We obtained an exclusive license to develop and commercialize ICLUSIG in Europe and other select countries.

ARIAD was subsequently acquired by Takeda Pharmaceutical Company Limited in 2017.

In December 2016, we entered into a Collaboration and License Agreement with Merus N.V.

Under this agreement, the parties have agreed to collaborate on the discovery of novel immuno-therapeutics using Agenus’ antibody discovery platforms.

In December 2016, we entered into a Collaboration and License Agreement with Merus.

Under this agreement, which became effective in January 2017, the parties have agreed to collaborate with respect to the research, discovery and development of bispecific antibodies utilizing Merus’ technology platform.

2 unchanged sentences

We continue to collaborate with Merus and leverage the Merus platform to develop a pipeline of novel agents, as we continue to hold worldwide exclusive development and commercialization rights to up to ten additional programs.

In January 2017, we entered into a Collaboration and License Agreement with Calithera Biosciences, Inc.

Under this agreement, we received an exclusive, worldwide license to develop and commercialize small molecule arginase inhibitors, including INCB01158 (CB-1158), which is currently in Phase II clinical trials, for multiple myeloma.

In October 2017, we entered into a Global Collaboration and License Agreement with MacroGenics.

5 unchanged sentences

In January 2020, we entered into a Collaboration and License Agreement with MorphoSys AG and MorphoSys US Inc., a wholly-owned subsidiary of MorphoSys AG, covering the worldwide development and commercialization of MOR208 (tafasitamab), an investigational Fc engineered monoclonal antibody directed against the target molecule CD19.

Under the terms of this agreement, we received exclusive commercialization rights outside of the United States, and

MorphoSys and we have co-commercialization rights in the United States, with respect to tafasitamab.

Under the terms of this agreement, we received exclusive commercialization rights outside of the United States, and MorphoSys and we have co-commercialization rights in the United States, with respect to tafasitamab.

In September 2021, we entered into a Collaboration and License Agreement with Syndax covering the worldwide development and commercialization of SNDX-6352 (axatilimab), Syndax’s anti-CSF-1R monoclonal antibody.

In March 2021, axatilimab was granted Orphan Drug Designation by the FDA for the treatment of chronic GVHD and a second designation in April 2021 for treatment of idiopathic pulmonary fibrosis.

The Agreement became effective in December 2021 with the expiration of the initial waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

Under the terms of this agreement, we received exclusive commercialization rights outside of the United States, and Syndax has co-commercialization rights in the United States with respect to axatilimab.

In December 2019, coronavirus disease of 2019, or COVID-19, was first reported in Wuhan, China.

In March 2020, the World Health Organization declared COVID-19 a pandemic.

We and our collaboration partners Lilly and Novartis initiated a number of clinical trials to address COVID-19.

In April 2020, we announced the initiation of a Phase III clinical trial (RUXCOVID) to evaluate the efficacy and safety of ruxolitinib plus standard-of-care (SoC), compared to SoC therapy alone, in patients not on mechanical ventilation and who have COVID-19 associated cytokine storm.

We sponsored this collaborative study in the United States and our collaboration partner Novartis International Pharmaceutical Ltd.

sponsored the study outside of the United States.

In December 2020, we announced initial results from RUXCOVID, where treatment with ruxolitinib plus SoC did not prevent complications compared to SoC treatment alone in patients with COVID-19 associated cytokine storm.

The RUXCOVID study has been completed and the data will be further analyzed to determine any potential impact on other studies of ruxolitinib in patients with COVID-19, including our Expanded Access Program in the United States, which allows eligible patients with severe COVID-19 associated cytokine storm to receive ruxolitinib.

In March 2021, results from a second Phase III clinical trial to evaluate the efficacy and safety of ruxolitinib plus SoC, compared to SoC therapy alone, in COVID-19 patients on mechanical ventilation and who have acute respiratory distress syndrome (ARDS), a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs were announced.

Ruxolitinib failed to reduce mortality due to any cause through Day 29 although in the U.S.

study population (91% of total study patients), there was a clinically and statistically significant improvement in mortality in each of the 5mg and 15mg ruxolitinib arms.

In April 2020, Lilly announced that it has entered into an agreement with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to study baricitinib as an arm in NIAID's Adaptive COVID-19 Treatment Trial (ACTT-2).

The study is investigating the efficacy and safety of baricitinib as a potential treatment for hospitalized patients diagnosed with COVID-19 in the United States, and Lilly is also planning an expansion to include Europe and Asia.

In September 2020, we and Lilly announced initial results from ACTT-2, where baricitinib in combination with remdesivir reduced the time to recovery in comparison with remdesivir alone.

Additional data announced in October 2020 showed that baricitinib plus remdesivir resulted in a numerical decrease in mortality through Day 29 compared to remdesivir alone, with a more pronounced reduction seen in more severely ill patients.

In November 2020, we and Lilly announced that the FDA issued an Emergency Use Authorization (EUA) for the distribution and emergency use of baricitinib to be used in combination with remdesivir in hospitalized adult and pediatric patients two years of age or older with suspected or laboratory confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

In December 2020, we and Lilly announced that data from ACTT-2 supportive of the EUA were published in the New England Journal of Medicine.

In July 2021, we and Lilly announced that the FDA broadened the EUA for baricitinib to allow for treatment with or without remdesivir.

The EUA now provides for the use of baricitinib for treatment of COVID-19 in hospitalized adults and pediatric patients

two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

In April 2021, we and Lilly announced that the primary endpoint was not met in COV-BARRIER, the Phase III randomized, double-blind, placebo–controlled study to evaluate the efficacy and safety of baricitinib in hospitalized adults not on mechanical ventilation and who have COVID-19.

There was, however, a 38% reduction in mortality by Day 28 in patients treated with baricitinib in addition to SoC.

In August 2021, we and Lilly announced new data from an additional cohort of 101 adult patients from the COV-BARRIER trial.

In this sub-study, patients with COVID-19 on mechanical ventilation or extracorporeal membrane oxygenation (ECMO) who received baricitinib plus standard of care were 46% less likely to die by Day 28 compared to patients who received placebo plus standard of care.

Incyte’s Approach to Drug Discovery and Development

Our productivity in drug discovery is primarily a result of our core competency in medicinal chemistry which is tightly integrated with, and supported by, an experienced team of biologists and pharmaceutical scientists with expertise in multiple therapeutic areas.

In addition to our small molecules expertise, we have added a biologics discovery capability in-house and have expanded our discovery scope to include bispecific antibodies through a collaboration with Merus.

This discovery team operates in concert with an equally experienced drug development organization with expertise in clinical sciences, statistics, and regulatory affairs.

Our drug development organization manages our clinical programs and utilizes clinical research organizations (CROs), expert scientific advisory boards, and leading consultants and suppliers as appropriate to ensure our clinical trials are conducted efficiently, effectively, and in accordance with regulatory and compliance guidelines.

To succeed in our objective to discover and advance novel therapeutics that address serious unmet medical needs, we have established a broad range of discovery capabilities in-house, including target validation, high-throughput screening, medicinal chemistry, computational chemistry, pharmacological and translational sciences, ADME (absorption, distribution, metabolism and excretion) and toxicology assessment.

To succeed in our objective to discover and advance novel therapeutics that address serious unmet medical needs, we have established a broad range of discovery capabilities in-house, including target validation, high-throughput screening, medicinal chemistry, computational chemistry, structural biology, pharmacological and translational sciences, ADME (absorption, distribution, metabolism and excretion) and toxicology assessment.

We augment these capabilities through collaborations with academic and contract laboratory resources with relevant expertise.

We are complementing these collaborations by establishing in-house pharmacology, ADME and CMC capabilities.

Driven by a target- and pathway-centric discovery process, our pipeline has grown and is currently focused primarily in the area of oncology.

Driven by a target- and pathway-centric discovery process, our pipeline has grown and is currently focused primarily in targeted oncology.

We conduct a limited number of discovery programs in parallel at any one time.

This focus allows us to allocate resources to our selected programs at a level that we believe is competitive with larger pharmaceutical companies.

We continually modify the resourcing of our discovery efforts with the goals of maximizing information content when and where we need it and ensuring that each program, regardless of stage, is executed in the most efficient and data-rich manner possible.

We resource our discovery efforts with the goals of maximizing information content when and where we need it and ensuring that each program, regardless of stage, is executed in the most efficient and data-rich manner possible.

We believe this approach has played a critical role in the development of our product portfolio.

Once our compounds reach clinical development, our objective is to rapidly progress the lead candidate into a proof-of-concept clinical trial to quickly assess the therapeutic potential of the clinical candidate itself as well as its underlying mechanism of action.

This information is then used to evaluate the compound’s development opportunities, identify the most appropriate indication or indications to pursue, and develop a clinical and regulatory plan to advance the molecule forward.

Once our compounds reach clinical development, our objective is to rapidly progress the lead candidate into a proof-of-concept clinical trial to assess quickly the therapeutic potential of the clinical candidate itself as well as its underlying mechanism of action.

This information is then used to evaluate the compound’s development opportunities, identify the most appropriate indication(s) to pursue, and develop a clinical and regulatory plan to advance the molecule.

Our development teams are responsible for ensuring that our clinical candidates are expeditiously progressed through clinical safety, proof-of-concept, and formal efficacy/pivotal trials.

Our development teams include employees with expertise in drug development, including clinical trial design, statistics, regulatory affairs, medical affairs, pharmacovigilance and project management.

We have also built internal process chemistry and formulation teams that work closely with external GMP contract manufacturers to support our drug development efforts.

We have also built internal chemistry, manufacturing and controls, and formulation teams that work closely with external GMP contract manufacturers to support our drug development efforts.

Incyte’s Commercial Strategy

1 unchanged sentence

We currently commercialize four compounds in the United States, three in Europe and one in Japan.

In November 2011, we received regulatory approval of JAKAFI (ruxolitinib) in the United States for the treatment of intermediate or high-risk myelofibrosis.

In December 2014, JAKAFI was approved for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

In May 2019, JAKAFI was approved for the treatment of steroid‐refractory acute GVHD in adult and pediatric patients 12 years and older.

In September 2021, JAKAFI was approved for the treatment of chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

As a result of these approvals, we have focused on increasing utilization of JAKAFI in these patient populations.

In April 2020, we received regulatory approval of PEMAZYRE (pemigatinib) in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 fusion or other rearrangement.

We are focused on increasing the utilization of molecular profiling in CCA to support identification of appropriate patients for PEMAZYRE.

In March 2021, PEMAZYRE was approved by the Japanese Ministry of Health, Labour and Welfare for the treatment of patients with unresectable biliary tract cancer with an FGFR2 fusion gene, worsening after cancer chemotherapy.

Also in March 2021, PEMAZYRE was approved by the European Commission for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

In January 2020, we and MorphoSys AG entered into a collaboration and license agreement to further develop and commercialize MorphoSys' proprietary anti-CD19 antibody tafasitamab globally.

In July of 2020, MONJUVI (tafasitamab-cxix), in combination with lenalidomide, was FDA approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

MONJUVI is being co-commercialized by us and MorphoSys in the United States.

In August 2021, the European Commission granted conditional marketing authorization for MINJUVI (tafasitamab) in combination with lenalidomide, followed by MINJUVI monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant.

In September 2021, we received regulatory approval of OPZELURA (ruxolitinib) cream in the United States for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

We established Incyte Dermatology as a new commercial franchise, which includes the marketing, medical, sales and operational infrastructure, to support the commercialization of OPZELURA in the United States.

ICLUSIG is approved in the European Union for the treatment of adult patients with CML who are resistant to dasatinib or nilotinib;

who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.

ICLUSIG is also indicated in adult patients with Philadelphia positive AML who are resistant to dasatinib;

who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.

We are focused on increasing the utilization of ICLUSIG in this patient population within our territory as appropriate.

We are continuing to expand our marketing, medical and operational infrastructure within the United States and outside of the United States to prepare for potential approval of other products.

For certain other compounds, including rights to ruxolitinib outside the United States and global rights to capmatinib, which have both been licensed to Novartis, and global rights to baricitinib, which have been licensed to Lilly, we have established and may in the future establish collaborations or strategic relationships to support development and commercialization in certain territories or therapeutic areas where we do not have or do not want to build expertise.

believe the key benefits to entering into such strategic relationships include the potential to expedite the development and commercialization of certain of our compounds, as well as the opportunity to receive upfront payments and future milestones and royalties in exchange for certain rights to those compounds.

These commercialized products are sold to specialty and retail pharmacies, specialty distributors and wholesalers in the United States in addition to retail pharmacies, hospital pharmacies, distributors and an exclusive wholesaler outside of the United States.

We continue to expand our marketing, medical and operational infrastructure within the United States and outside of the United States to support the commercial launch of recently approved products and to prepare for potential approval of other products.

For certain compounds, we have established and may in the future establish collaborations or strategic relationships to support development and commercialization in certain territories or therapeutic areas where we do not have or do not want to build expertise.

We believe the key benefits to entering into such strategic relationships include the potential to expedite the development and commercialization of certain of our compounds, as well as the opportunity to receive upfront payments and future milestones and royalties in exchange for certain rights to those compounds.

Refer to the “License Agreements and Business Relationships” section above for information regarding our collaborations and strategic relationships.

Patents and Other Intellectual Property

5 unchanged sentences

The following table sets forth the status of the patents and patent applications in the United States, the European Union, and Japan for our approved medicines and for those compounds in our portfolio that have been submitted to regulatory authorities seeking approval or are in registration-directed clinical trials:

Drug/Drug Candidate (Target)

Status of U.S.

Drug/Drug Candidate (Target) Status of U.S.

Composition of Matter Patent Estate

7 unchanged sentences

Granted and pending (2028) 9

baricitinib (JAK)

Granted and pending (2030) 5

Granted and pending (2032)

Granted and pending (2033)

itacitinib (JAK)

Granted and pending (2032) 4

Granted and pending (2031) 4

capmatinib (MET)

Granted and pending (2027) 5

Granted and pending (2027) 4

baricitinib (JAK) Granted and pending (2030) 5

Granted and pending (2032) Granted and pending (2033)

itacitinib (JAK) Granted and pending (2032) 4

Granted and pending (2031) 4

parsaclisib (PI3Kδ)

Granted and pending (2031) 4

capmatinib (MET) Granted and pending (2027) 5

Granted and pending (2027) 5

Granted and pending (2032)

pemigatinib (FGFR)

parsaclisib (PI3Kδ) Granted and pending (2033) 4

Granted and pending (2032) 4

pemigatinib (FGFR) Granted and pending (2035) 5

Granted and pending (2033) 5

ponatinib (BCRABL)

Granted and pending (2036)

ponatinib (BCRABL) Granted and pending (2026)

retifanlimab (PD-1) 6

10 unchanged sentences

Granted and pending (2034) 4

Ruxolitinib cream formulation patents are issued in the United States, European Union and Japan with anticipated expiration dates of 2031 respectively, not including patent term extensions that will be sought upon regulatory approval.

Once-a-day (QD) ruxolitinib formulation patents are issued in the United States and the European Union, but pending in Japan with anticipated expiration dates of 2033 respectively, not including patent term extensions that will be sought upon regulatory approval.

Ruxolitinib cream formulation patents are issued in the United States, European Union and Japan with anticipated expiration dates of 2031 in each jurisdiction.

This does not include patent term extensions which we plan to seek upon further regulatory approval.

I n late 2022, we received an issued patent and allowed claims to the treatments of atopic dermatitis and vitiligo, respectively, with anticipated expiration dates of 2040.

Once-a-day (QD) ruxolitinib formulation patents are issued in the United States, the European Union and Japan, with anticipated expiration dates of 2033 in each of these jurisdictions, not including patent term extensions that we plan to seek upon regulatory approval.

Subject to the payment of maintenance fees.

Respective patent term extension/supplementary protection certificate (SPC) will be sought upon approval by the respective regulatory agency.

Patent term extension has been applied for and being sought.

We plan to seek respective patent term extension/supplementary protection certificate (SPC) upon approval by the respective regulatory agency.

Patent term extension/SPC has been applied for and being sought.

Retifanlimab licensed from MacroGenics.

1 unchanged sentence

Axatilimab licensed from Syndax.

Ruxolitinib phosphate salt patents are issued in the United States, European Union and Japan with anticipated expiration dates of mid-2028, not including patent term extensions.

Ruxolitinib phosphate salt patents are issued in the United States, European Union and Japan with anticipated expiration dates of late-2028 in the United States and mid-2028 in the European Union and Japan, not including patent term extensions.

Patents extend for varying periods according to the date of patent filing or grant and the legal term of patents in the various countries where patent protection is obtained.

1 unchanged sentence

We may seek to license rights relating to technologies, drug candidates or drug products in connection with our drug discovery and development programs and commercialization activities.

Under these licenses, such as our licenses

from Agenus, ARIAD/Takeda, Calithera, MacroGenics, MorphoSys, Merus, and Syndax, we may be required to pay up-front fees, license fees, milestone payments and royalties on sales of future products.

Under these licenses, such as our licenses from Agenus, ARIAD/Takeda, MacroGenics, MorphoSys, Merus, and Syndax, we may be required to pay up-front fees, license fees, milestone payments and royalties on sales of future products.

Although we believe our rights under patents and patent applications provide a competitive advantage, the patent positions of pharmaceutical and biotechnology companies are highly uncertain and involve complex legal and factual questions.

60 unchanged sentences

We cannot be sure that submission of an IND will result in the FDA allowing clinical trials to commence.

Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators and in accordance with Good Clinical Practice regulations covering the protection of human subjects.

Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators and in accordance with Good Clinical Practice (GCP) regulations covering the protection of human subjects.

These regulations require all research subjects to provide informed consent.

9 unchanged sentences

Under the SPA procedure, a sponsor may seek the FDA’s agreement on the design and size of a clinical trial intended to form the primary basis of an effectiveness claim.

If the FDA agrees in writing, its agreement may not be changed after the trial begins, except when agreed by FDA or in limited circumstances, such as when a substantial scientific issue essential to determining the safety and effectiveness of a drug candidate is identified after a

Phase III clinical trial is commenced and agreement is obtained with the FDA.

If the outcome of the trial is successful, the sponsor will ordinarily be able to rely on it as the primary basis for approval with respect to effectiveness.

50 unchanged sentences

Manufacturing facilities are always subject to inspection by the applicable regulatory authorities.

quality standards as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, or ICH, FDA and the European Medicines Agency.

We and our third-party manufacturers are subject to current Good Manufacturing Practices, or GMP, which are extensive regulations governing manufacturing processes, including but not limited to stability testing, record keeping and quality standards as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, or ICH, FDA and the European Medicines Agency.

Similar regulations are in effect in other countries.

19 unchanged sentences

Any applicable state or local regulations may hinder our ability to market, or increase the cost of marketing, our products in those states or localities.

The FDA’s policies may change and additional government regulations may be enacted which could impose additional burdens or limitations on our ability to market products after approval.

The FDA’s policies may change and additional government regulations may be enacted that could impose additional burdens or limitations on our ability to market products after approval.

Moreover, increased attention to the containment of health care costs in the United States and in foreign markets could result in new government regulations which could have a material adverse effect on our business.

1 unchanged sentence

Marketing Exclusivity

forms of an existing drug if new clinical investigations that were conducted or sponsored by the applicant are essential to the approval of the supplemental application.

The FDA may grant five years of exclusivity in the United States for the approval of NDAs for new chemical entities, and three years of exclusivity for supplemental NDAs, for among other things, new indications, dosages or dosage forms of an existing drug if new clinical investigations that were conducted or sponsored by the applicant are essential to the approval of the supplemental application.

Additionally, six months of marketing exclusivity in the United States is available if, in response to a written request from the FDA, a sponsor submits and the agency accepts requested information relating to the use of the approved drug in the pediatric population.

10 unchanged sentences

Certain countries outside of the United States have a process that requires the submission of a clinical trial application, or CTA, much like an IND prior to the commencement of human clinical trials.

In Europe, a CTA must be submitted for each trial to the competent national health authority and to independent ethics committees in each country in which a company plans to conduct clinical trials.

Once the CTA is approved in accordance with a country’s requirements, clinical trial development may proceed in that country and are conducted in accordance with GCP and other applicable regulatory requirements.

In the European Union, a CTA must be submitted for each trial to the competent health authority and to independent ethics committees by national procedure for a single country trial or by EMA submission portal CTIS for a multinational study.

Once the CTA is approved in accordance with the requirements in the concerned countries, clinical trial development may proceed in those countries and are conducted in accordance with GCP and other applicable regulatory requirements.

To obtain regulatory approval of an investigational drug under EU regulatory systems, we must submit a marketing authorization application (MAA).

This application is similar to the NDA in the United States, with the exception of, among other things, regional and/or country-specific document requirements.

Drugs can be authorized in the EU by using (i) the centralized authorization procedure, (ii) the mutual recognition procedure, (iii) the decentralized procedure or (iv) national authorization procedures.

Drugs can be authorized in the EU by using the centralized, mutual recognition, decentralized or national authorization procedures described below.

The European Medicines Agency implemented the centralized procedure for the approval of human drugs to facilitate marketing authorizations that are valid throughout the EU.

1 unchanged sentence

Under the centralized procedure, the maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use).

A positive opinion on the MAA by the CHMP then needs to be endorsed by the European Commission.

A positive opinion on the MAA by the CHMP then needs to be endorsed by the European Commission within approximately 67 days.

Accelerated assessment might be granted by the CHMP in exceptional cases, in which case the EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days (excluding clock stops) and the opinion issued thereafter.

23 unchanged sentences

In July 2018, we purchased land located in Yverdon, Switzerland for construction of a large molecule production facility to manufacture biologic drug substances for our drug candidates.

Construction activity commenced in July 2018 and we currently expect the facility to be GMP approved in the second half of 2022, after the inspection and approval from the competent authorities.

Construction activity commenced in July 2018, and inspection from competent authorities was finalized in March 2022, and in June 2022 Swissmedic authorities granted the GMP drug manufacturing license for this facility.

The Yverdon facility started to manufacture MONJUVI/MINJUVI drug substance during the fourth quarter of 2022.

The drug substance will be usable in patients after regulatory approval, which is currently expected in the first quarter of 2024 for the European market and in the fourth quarter of 2024 in the U.S.

Manufacturing of our Products

34 unchanged sentences

If delivery of material from their suppliers were interrupted for any reason or if they are unable to purchase sufficient quantities of raw materials used to manufacture our products and drug candidates, they may be unable to ship our products for commercial supply or to supply our drug candidates in development for clinical trials.

For example, currently raw materials used to manufacture ruxolitinib phosphate, the API in JAKAFI and OPZELURA, are supplied by

Chinese-based companies.

For example, currently raw materials used to manufacture ruxolitinib phosphate, the API in JAKAFI and OPZELURA, are supplied by Chinese-based companies.

As a result, an international trade dispute between China and the United States or any other actions by the Chinese government that would limit or prevent Chinese companies from supplying these materials would adversely affect our ability to manufacture and supply our products to meet market needs and have a material and adverse effect on our operating results.

17 unchanged sentences

We have continued to expand our recruitment searches to include organizations and websites dedicated to Black candidates.

We have partnered with Jopwell, to aid connections with Black and other underrepresented candidates for non-science jobs and we are participating in the reputable Scientific Mentoring & Diversity Program (SMDP) mentoring program that pairs primarily Black and Brown students, who are post baccalaureate and graduate students with mentors who work at biopharmaceutical companies.

We additionally post all of our open positions on the Historically Black Colleges and Universities career pages and participate in diversity career fairs with national organizations such as National Black MBA Association and National Sales Network in order to expand our recruitment reach.

We post all of our open positions on the Historically Black Colleges and Universities career pages and participate in diversity career fairs with national organizations such as National Black MBA Association and National Sales Network in order to expand our recruitment reach.

As part of our ESG goals in our 2022 incentive compensation plan, we also introduced a goal of ensuring that a minimum rate of 70% of all open positions being recruited in the United States have at least one Black or Hispanic candidate represented in the candidate pool.

We offer what we believe is a competitive compensation package, which allows 100% of global Incyte employees to participate in our annual incentive compensation plan as well as annual equity-based grants.

We seek to ensure our compensation package remains competitive by benchmarking against our peers several times annually as well as conducting twice per year compensation reviews to confirm that our employees are being compensated fairly, equitably and in accordance with our pay structures and job levels.

We seek to ensure our compensation package remains competitive by benchmarking against our peers several times annually as well as conducting annual compensation reviews to confirm that our employees are being compensated fairly, equitably and in accordance with our pay structures and job levels.

In addition, we offer what we believe is a competitive benefits package, which includes an option to participate in our Employee Stock Purchase Plan for both full-time and part-time employees working at least 20 hours per week.

4 unchanged sentences

We believe these professional opportunities enhance our colleagues’ skills, career aspirations and job satisfaction as well as provide personal enrichment.

As of December 31, 2021, we had 2,094 employees representing an 18% increase over our 1,773 employees as of the end of the prior year.

This growth is largely as result of preparations for the commercial launch of OPZELURA

(ruxolitinib) cream in the second half of 2021.

Among our employees, 989 are in research and development, 187 in medical affairs, 638 in sales and marketing and 280 in operations support, finance and administrative positions.

As of December 31, 2022, we had 2,324 employees, representing an increase of approximately 11% over our 2,094 employees as of the end of the prior year.

This growth is largely a result of continued expansion of our global commercial reach for the launch of OPZELURA (ruxolitinib) cream.

Among our employees, 1,099 are in research and development, 201 in medical affairs, 676 in sales and marketing and 348 in operations support and administrative positions.

Geographically, 72% of our employees were based in the United States and Canada, 25% in Europe and 3% employees were based in Asia.

In terms of gender diversity, 52% are female and 48% are male.

None of our employees are covered by collective bargaining agreements, and management considers relations with our employees to be good.

Our employees in Belgium and Spain are covered by collective agreements, and management considers relations with our employees to be good.

Available Information

3 unchanged sentences

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