- Data demonstrates the potential for INCA033989 to modify
disease by directly inhibiting and eliminating oncogenic mutCALR
cells, while sparing healthy cells and restoring normal blood cell
production
- In high-risk patients with essential thrombocythemia (ET) with
a CALR mutation (mutCALR), 86% of INCA033989-treated patients at
doses 400 mg and above achieved a complete or partial hematologic
response with the majority (82%) realizing a complete response
- A reduction in peripheral blood mutCALR variant allele
frequency (VAF) was observed in 89% of evaluable patients
correlating with hematologic response
- Initial results demonstrate a favorable safety profile – no
dose limiting toxicities were reported, a maximum tolerated dose
was not reached and 98% of patients remained on treatment
- Incyte will host an in-person analyst and investor event
highlighting this data at EHA today, Sunday, June 15, 2025, from
6:00 - 7:30 a.m. EDT (12:00 -1:30 p.m. CEST)
Incyte (Nasdaq:INCY) today announced the first clinical data
from two studies evaluating the safety, tolerability and efficacy
of INCA033989, a novel, first in class, Incyte-discovered, targeted
monoclonal antibody in patients with mutant calreticulin
(mutCALR)-expressing myeloproliferative neoplasms (MPNs). These
data – featured today in the Late-Breaking Oral Session (#LB4002)
at the European Hematology Association 2025 (EHA2025) Congress in
Milan, Italy – focus on the dose escalation portion of the studies
in patients with high risk essential thrombocythemia (ET) who are
resistant/intolerant to prior cytoreductive therapy.
The studies evaluated the safety and efficacy of INCA033989 in
patients with ET as measured by hematologic response and reduction
in mutCALR variant allele frequency (VAF).
Results as of April 4, 2025, showed rapid and durable
normalization of platelet counts across all dose levels, with a
trend toward improved responses in higher doses (>400 mg), in patients with ET treated with
INCA033989. Notably, 86% of patients at doses 400 mg and above
achieved a complete or partial hematologic response, with the
majority (82%) of patients achieving complete response. Eighty-nine
(89) percent of evaluable patients (34/38) showed a reduction in
mutCALR VAF from baseline. A partial molecular response (>50%
VAF reduction) was observed in 21% of evaluable patients (8/38)
after only 3 cycles of treatment.
An exploratory study using single-cell DNA (scDNA) sequencing
showed that INCA033989 directly targets and reduces cells carrying
mutCALR. This reduction was seen in early blood-forming
(CD34-positive) cells and cells in the myeloid-erythroid (ME)
lineage. At the same time, there was a clear increase in healthy
(wild-type CALR) cells, suggesting that the treatment supports the
return of normal blood production. Bone marrow biopsies further
confirmed these effects showing fewer megakaryocytes with mutCALR
protein and a notable increase in megakaryocytes without mutCALR
protein. Together, these findings demonstrate the selectivity of
INCA033989, allowing for normalization of healthy hematopoiesis and
disease modification.
“The late-breaking data presented today highlight the impact of
INCA033989, a novel agent that selectively targets mutant CALR, to
inhibit and eliminate cancer-causing cells in patients with
essential thrombocythemia (ET), while sparing healthy cells and
normalizing healthy blood production," said Pablo J. Cagnoni, M.D.,
President, Head of Research and Development, Incyte. “These
findings, and the further development of INCA033989, offer the
potential to significantly transform the treatment of patients with
CALR-mutant myeloproliferative neoplasms (MPNs).”
The results (N=49) showed that INCA033989 was well tolerated
across all dose cohorts (24 to 2,500 mg), with no dose-limiting
toxicities observed. Only one (1) patient discontinued treatment,
and only one (1) dose reduction due to treatment-emergent adverse
events (TEAEs) was observed. No infusion interruptions due to TEAEs
were reported, and a maximum tolerated dose was not reached.
Forty-two (42) patients across the dose cohorts reported a TEAE.
The most common TEAEs were fatigue (26.5%) and upper respiratory
tract infection (20.4%), all of which were Grade ≤2. Thirteen (13)
patients had Grade >3 TEAEs, with
transient asymptomatic lipase increase as the most common (6%).
“mutCALR is the second most common oncogenic driver of MPNs, yet
the therapeutic landscape lacks a targeted agent for mutCALR
expressing MPNs. Currently, ET treatments aim to prevent vascular
complications and improve symptoms but are limited by toxicity and
tolerability issues,” said John Mascarenhas, M.D., Professor of
Medicine at the Icahn School of Medicine at Mt. Sinai and Director,
Center of Excellence for Blood Cancers and Myeloid Disorders, The
Tisch Cancer Institute. “These data support the hypothesis that
INCA033989 has the potential not only to normalize platelet counts
and provide rapid and durable hematologic responses – but to induce
molecular responses, which could potentially change the natural
history of the disease.”
Additional data from the INCA033989 study in patients with
myelofibrosis will be submitted for presentation at a future
medical meeting. Discussions with regulatory authorities are
planned with the goal to initiate a Phase 3 study by early
2026.
More information regarding the EHA2025 Congress and the data
from Incyte’s hematology/oncology portfolio being featured at the
meeting can be found on the EHA website:
https://ehaweb.org/congress/eha2025-congress.
Incyte Conference Call and Webcast
Incyte will host an in-person analyst and investor event on
Sunday, June 15, 2025, from 6:00 - 7:30 a.m. ET (12:00 - 1:30 p.m.
CEST) to discuss key mutCALR data presented at EHA.
The event will be webcasted and can be accessed via the Events
and Presentations tab of the Investor section of Incyte.com and it
will be available for replay for 30 days.
About Myeloproliferative Neoplasms
Myeloproliferative neoplasms (MPNs) are a closely related group
of blood cancers in which the bone marrow functions abnormally. The
bone marrow is where the body’s blood cells are made. MPNs are
progressive blood cancers that can strike anyone at any age, but
they are more common in older adults. Estimates of the prevalence
of MPNs vary, but analysis of claims data suggests there may be as
many as 200,000 people in the U.S. living with the most prevalent
MPNs: myelofibrosis, polycythemia vera or essential thrombocythemia
(ET).1
About Mutations in Calreticulin (mutCALR)
Calreticulin (CALR) is a protein involved in the regulation of
cellular calcium levels and normal protein folding. Somatic, or
non-inherited, DNA mutations in the CALR gene (mutCALR) can result
in abnormal protein function and lead to the development of
myeloproliferative neoplasms (MPNs),2 a closely related group of
clonal blood cancers in which the bone marrow functions abnormally,
overproducing blood cells.3,4 Among two types of MPNs, essential
thrombocythemia (ET) and myelofibrosis (MF), mutCALR drives 25-35%
of all cases.2,3 There are approximately 60,000 patients in the
U.S. and Europe with mutCALR positive ET.5
Incyte is at the forefront of developing novel therapies for
patients with mutCALR ET or MF that target only malignant cells,
sparing normal cells, including INCA033989, a first-in-class,
mutCALR-specific therapy.
About the INCA033989 Trial Program
The clinical trial program for INCA033989 includes two
multicenter, open-label Phase 1 studies, INCA33989-101
(NCT05936359) and INCA33989-102 (NCT06034002), enrolling ~225
patients outside of the U.S. and ~140 patients in the U.S.,
respectively. The studies are evaluating the safety, tolerability,
dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)
and/or recommended dose(s) for expansion (RDE) of INCA033989
administered as a monotherapy or in combination with ruxolitinib in
patients with myeloproliferative neoplasms (MPNs), including
essential thrombocythemia (ET) and myelofibrosis (MF). The intent
of Part 1A (dose escalation) is to identify the MTD and/or the RDE
of INCA033989 among patients with MF and ET. In Part 1A INCA033989
is administered intravenously every two weeks at a protocol defined
dose ranging from 24 mg. to 2,500 mg. In Part 1B (dose expansion),
INCA033989 is administered at the RDE(s) identified during Part
1A.
The primary endpoint of the studies focuses on safety and
tolerability as measured by: the number of participants with DLTs
up to 28 days, the number of participants with treatment-emergent
adverse events (TEAEs) up to 3 years and 60 days, and the number of
participants with TEAEs leading to dose modification or
discontinuation up to 3 years and 60 days. Secondary endpoints
include response rates, mean change of ET total symptom score from
baseline, percentage of MF patients achieving spleen volume
reduction, MF patient anemia response, mean change in
disease-related allele burden and various pharmacokinetics measures
up to 3 years and 60 days.
For more information on the study, please visit:
https://clinicaltrials.gov/study/NCT05936359 and
https://clinicaltrials.gov/study/NCT06034002.
About Incyte
A global biopharmaceutical company on a mission to Solve On.,
Incyte follows the science to find solutions for patients with
unmet medical needs. Through the discovery, development and
commercialization of proprietary therapeutics, Incyte has
established a portfolio of first-in-class medicines for patients
and a strong pipeline of products in Oncology and Inflammation
& Autoimmunity. Headquartered in Wilmington, Delaware, Incyte
has operations in North America, Europe and Asia.
For additional information on Incyte, please visit Incyte.com or
follow us on social media: LinkedIn, X, Instagram, Facebook,
YouTube.
Forward-Looking Statements
Except for the historical information set forth herein, the
matters set forth in this press release, including statements
regarding the presentation of data for Incyte’s anti-mutCALR
monoclonal antibody (INCA033989), the potential this monoclonal
antibody offers for patients, and expectations regarding ongoing
and future clinical trials contain predictions, estimates, and
other forward-looking statements.
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: further research and
development and the results of clinical trials possibly being
unsuccessful or insufficient to meet applicable regulatory
standards or warrant continued development; the ability to enroll
sufficient numbers of subjects in clinical trials and the ability
to enroll subjects in accordance with planned schedules;
determinations made by the FDA, EMA and other regulatory agencies;
Incyte’s dependence on its relationships with and changes in the
plans of its collaboration partners; the efficacy or safety of
Incyte’s products and the products of Incyte’s collaboration
partners; the acceptance of Incyte’s products and the products of
Incyte’s collaboration partners in the marketplace; market
competition; unexpected variations in the demand for Incyte’s
products and the products of Incyte’s collaboration partners; the
effects of announced or unexpected price regulation or limitations
on reimbursement or coverage for Incyte’s products and the products
of Incyte’s collaboration partners; sales, marketing, manufacturing
and distribution requirements, including Incyte’s and its
collaboration partners’ ability to successfully commercialize and
build commercial infrastructure for newly approved products and any
additional products that become approved; greater than expected
expenses, including expenses relating to litigation or strategic
activities; variations in foreign currency exchange rates; and
other risks detailed in Incyte’s reports filed with the Securities
and Exchange Commission, including its annual report on form 10-K
and our quarterly report on Form 10-Q for the quarter ended March
31, 2025. Incyte disclaims any intent or obligation to update these
forward-looking statements.
_____________________________ 1 Data on file
2 Raghavan, M., Wijeyesakere S.J., Peters
L.R., Del Cid N. (2013) Calreticulin in the immune system: ins and
outs. Trends in Immunology, 34(1):13-21. Link to source
(https://www.cell.com/trends/immunology/abstract/S1471-4906(12)00131-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1471490612001317%3Fshowall%3Dtrue)
3 Nangalia J. Massie C.E., Baxter E.J.,
Nice F.L., et al. (2013) Somatic CALR mutations in
myeloproliferative neoplasms with nonmutated JAK2. New England
Journal of Medicine, 369(25):2391-2405. Link to source
(https://www.nejm.org/doi/10.1056/NEJMoa1312542?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov)
4 Klampfl T., Gisslinger, H., Harutyunyan
A.S., et al. (2013) Somatic mutations of calreticulin in
myeloproliferative neoplasms. New England Journal of Medicine,
369(25):2379-2390. Link to source
(https://www.nejm.org/doi/10.1056/NEJMoa1311347?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov)
5 Epidemiology Source: DRG, Prevalence
2026.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250615304440/en/
Incyte Contacts:
Media media@incyte.com Investors ir@incyte.com
Incyte (NASDAQ:INCY)
Historical Stock Chart
Von Jun 2025 bis Jul 2025
Incyte (NASDAQ:INCY)
Historical Stock Chart
Von Jul 2024 bis Jul 2025
