Incyte Announces Preliminary Results of a Phase I/II Study of Combination Immunotherapy in Patients with Melanoma

  Incyte Announces Preliminary Results of a Phase I/II Study of Combination
  Immunotherapy in Patients with Melanoma

  *Clinical data suggest anti-tumor synergy between Incyte’s IDO1 inhibitor
    INCB24360 and ipilimumab described in an ASCO poster highlights session
  *Among immunotherapy-naïve patients receiving INCB24360 combined with
    ipilimumab, 42 percent had an objective response and 75 percent achieved
    disease control
  *IDO1 inhibitor-based combination therapy represents a promising and
    potentially synergistic approach to immuno-oncology

 Incyte to host a webcast for investors featuring key results from this trial
                     on Monday, June 2, at 6:45 p.m. CDT

2014 ASCO Annual Meeting

Business Wire

CHICAGO -- June 2, 2014

Incyte Corporation (Nasdaq: INCY) today announced that preliminary results
from an ongoing Phase I/II study of INCB24360, its oral indoleamine
2,3-dioxygenase 1 (IDO1) inhibitor, combined with ipilimumab in patients with
unresectable or metastatic melanoma were presented at the 50^th Annual Meeting
of the American Society of Clinical Oncology (ASCO), May 30 to June 3, 2014,
in Chicago. The poster reported initial findings showing that the combination
was generally well tolerated and produced evidence of clinical response.

In the study, 42 percent (5/12) of immunotherapy-naïve patients who received
ipilimumab with INCB24360 at 25 mg or 50 mg twice-daily demonstrated an
objective response (complete response + partial response) and 75 percent
(9/12) achieved disease control (complete response + partial response + stable
disease) as assessed using immune-related response criteria (irRC). One
patient with pulmonary metastases treated with ipilimumab and INCB24360 50 mg
twice-daily experienced a complete response. Immune-related adverse events
observed in these cohorts were generally mild-to-moderate (Grade 1 or Grade
2). Grade 3 or 4 immune related adverse events were qualitatively similar to
ipilimumab monotherapy and were generally manageable and reversible.

“In addition to seeing disease control among the 12 immunotherapy-naïve
patients, many of these patients also experienced substantial reduction in
tumor burden,” said Geoffrey T. Gibney, M.D., Moffitt Cancer Center, who
presented the study findings. “These preliminary data suggest INCB24360 may
improve patient outcomes with manageable toxicity when combined with
ipilimumab.”

“Immune-targeted combination therapy represents one of the most promising
approaches in oncology and our preclinical data suggested that combination of
an IDO1 inhibitor with checkpoint inhibitors could have significant anti-tumor
synergy,” said Hervé Hoppenot, President and Chief Executive Officer, Incyte.
“The synergistic activity observed between INCB24360 and ipilimumab increases
our confidence in the value of investigating other immunotherapy combinations
with INCB24360 in multiple tumor types.”

The poster for this presentation can be accessed at 2014 ASCO - INCB24360
poster.

About the Study

The ASCO presentation described results from the open-label, dose escalation
portion of the ongoing Phase I/II study evaluating the combination of a
standard regimen of ipilimumab with oral INCB24360. Study endpoints included
safety and tolerability, objective response rate (assessed using irRC and
RECIST 1.1 criteria every nine weeks), duration of response, overall and
progression-free survival, and IDO1 inhibition.

Additional Safety and Efficacy Findings

Initially, seven patients were enrolled in a cohort receiving ipilimumab with
INCB24360 300 mg twice-daily. Five of these patients developed clinically
significant (Grade 3 or 4) alanine aminotransferase (ALT) elevations and
enrollment was stopped. The ALT elevations observed in the patients receiving
the 300 mg dose were reversible with corticosteroids and treatment
discontinuation. Although all patients in the 300 mg twice-daily cohort were
discontinued before response could be fully evaluated, six of the seven
patients were alive after one year, including three who have not received
subsequent checkpoint inhibitor immunotherapy. The study was amended to
evaluate lower doses of INCB24360.

Seventeen patients were enrolled in the INCB24360 25 mg twice-daily and 50 mg
twice-daily cohorts. During the dose limiting toxicity (DLT) observation
periods, one patient in the 25 mg cohort who had extensive liver metastases
prior to entering the trial experienced a DLT (Grade 3 AST elevation), and two
patients in the 50 mg cohort experienced a DLT (Grade 3 diarrhea and Grade 3
ALT elevation). In both cohorts, immune-related treatment-emergent adverse
events were generally Grade 1 or Grade 2 and manageable with continued dosing
or temporary dose interruption.

Twelve patients who were treatment-naïve for advanced or metastatic disease
were enrolled in the INCB24360 25 mg twice-daily and 50 mg twice-daily
cohorts. Eight of these immunotherapy-naïve patients experienced a reduction
in tumor burden, and most reductions were durable with continued therapy. As
of the data cutoff, the majority of immunotherapy-naïve patients are
continuing on study therapy or have experienced a prolonged period without the
need for subsequent therapy.

Of the five patients who received prior immunotherapy for advanced or
metastatic disease, two (40 percent) achieved stable disease by irRC.

Duration of disease control ranged from 60 to more than 379 days (ongoing).

Pharmacodynamic effects with INCB24360 25 mg BID and 50 mg BID were similar to
those that were sufficient in preclinical models to achieve maximal
therapeutic effect. IDO1 inhibition in this study was consistent with that
observed in the phase I open-label study,^1 suggesting that there was no
pharmacodynamic interaction with ipilimumab.

About INCB24360

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has
been shown to induce regulatory T cell generation and activation, and allow
tumors to escape immune surveillance. INCB24360 is an orally bioavailable
small molecule inhibitor of IDO1 that has nanomolar potency in both
biochemical and cellular assays and has demonstrated potent activity in
enhancing T lymphocyte, dendritic cell and natural killer cell responses in
vitro, with a high degree of selectivity. INCB24360 has been shown to be
active in mouse models of cancer as a single agent and in combination with
cytotoxic and immunotherapy agents, and its ability to reduce tumor growth is
dependent on a functional immune system – consistent with its proposed
mechanism of action. A Phase I dose-escalation trial demonstrated that
INCB24360 results in greater than 90 percent inhibition of IDO1 activity at
generally well-tolerated doses.

In addition to the Phase I/II study in metastatic melanoma in combination with
ipilimumab (www.clinicaltrials.gov Identifier: NCT01604889), described in the
ASCO presentation, Incyte has also established three clinical research
agreements to study INCB24360 in combination with the investigational
anti-PD-1 immunotherapy checkpoint inhibitor MK-3475 (Merck), the
investigational anti-PD-L1 immune checkpoint inhibitor MEDI 4736 (MedImmune),
and the investigational anti-PD-1 immune checkpoint inhibitor nivolumab
(Bristol-Myers Squibb).

About the Webcast

Incyte will host an investor meeting, which will be webcast live at 6:45 p.m.
CDT on June 2, 2014, and can be accessed at www.incyte.com under Investor
Relations, Events and Webcasts. A replay of the event will be available for 60
days.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical company
focused on the discovery, development and commercialization of proprietary
small molecule drugs, primarily in oncology. For additional information on
Incyte, please visit the Company’s website at www.incyte.com.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth
in this press release, including without limitation statements with respect to
the potential efficacy, safety and therapeutic value of, and Incyte’s plans
for, INCB24360, including that INCB24360 may improve patient outcomes with
manageable toxicity when combined with ipilimumab, contain predictions and
estimates and are forward-looking statements within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act of 1995.
These forward-looking statements are based on Incyte’s current expectations
and subject to risks and uncertainties that may cause actual results to differ
materially, including unanticipated developments in and risks related to the
efficacy or safety of INCB24360, the results of further research and
development, the high degree of risk and uncertainty associated with drug
development, clinical trials and regulatory approval processes, other market
or economic factors, competitive and technological advances, and other risks
detailed from time to time in Incyte's filings with the Securities and
Exchange Commission, including its Quarterly Report on Form 10-Q for the
quarter ended March 31, 2014. Incyte disclaims any intent or obligation to
update these forward-looking statements.

Links to third party websites or pages are provided for convenience only. Each
website is subject to its own terms of use, and Incyte encourages you to
consult these policy statements. Incyte has no control over third party sites
and does not endorse or recommend these sites, and expressly disclaims any
responsibility for the accuracy of content or opinions set forth in any third
party website or your use of that information.

Reference

     Beatty GL, et al. Phase I study of the safety, pharmacokinetics, and
     pharmacodynamics of the oral inhibitor of indoleamine 2,3-dioxygenase
1.  (IDO1) INCB024360 in patients with advanced malignancies. Presented at:
     2013 Annual Meeting of the American Society of Clinical Oncology; May
     31-June 4, 2013; Chicago, IL.

Contact:

Incyte Corporation
Pamela M. Murphy
Vice President, Investor Relations & Corporate Communications
+1 302-498-6944
 
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