Kiadis announces publication in Blood highlighting proof-of-concept
to enhance potency of anti-CD38 antibodies with Kiadis’ K-NK004,
recently licensed by Sanofi
CD38KO NK cell therapy has the potential to
maximize the efficacy of anti-CD38 against multiple myeloma
Amsterdam, The Netherlands, July 22,
2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext
Amsterdam and Brussels: KDS), a clinical stage
biopharmaceutical company developing innovative cell therapeutics
for life-threatening diseases, today announces publication of an
article in Blood, Journal of the American Society of Hematology.
The article describes the synergy of mbIL21 expanded NK cells
(FC21-NK) modified with a CD38 gene knockout together with an
anti-CD38 monoclonal antibody (mAb) for enhanced killing of
multiple myeloma cells.
The publication describes the use of the
CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded
peripheral blood K-NK cells, with 82% knock out efficiency. These
CD38KO K-NK cells were completely resistant to anti-CD38
antibody-induced fratricide. In addition, as compared to wild type
NK cells, the CD38KO K-NK cells showed superior persistence in
immune deficient mice pre-treated with anti-CD38 antibody, and
enhanced ADCC activity against CD38-expressing multiple myeloma
cell lines and primary multiple myeloma cells. Additionally,
analysis demonstrated that CD38KO K-NK cells have unique metabolic
reprogramming with higher mitochondrial respiratory capacity,
important in a hypoxic tumor micro-environment. Taken together,
these findings provide proof-of-concept that adoptive immunotherapy
using ex vivo expanded CD38KO K-NK cells has the potential to boost
anti-CD38 antibody activity in multiple myeloma.
Dean Lee, MD, PhD, co-author of the article,
Director of the Cellular Therapy and Cancer Immunology Program at
Nationwide Children’s Hospital and The Ohio State University
Comprehensive Cancer Center – Arthur G. James Cancer Hospital and
Richard Solove Research Institute commented, “This work was a great
opportunity to collaborate with Gabriel Ghiaur, MD, PhD, co-author
of the article and Assistant Professor of Oncology at The Sidney
Kimmel Comprehensive Cancer Center, Johns Hopkins University. By
combining the CRISPR/Cas9 technology with the FC21-NK cell platform
we were able to produce and test an engineered NK cell therapeutic
to address a recognized hurdle in immunotherapy of multiple
myeloma. The ease and efficiency of this approach increases its
potential to be translated to the clinic.”
Robert Friesen, chief scientific officer of
Kiadis commented, “We are excited to see the published results of
this scientific study, the proof-of-concept that targeted knockout
of CD38 in highly stimulated NK cells can be synergistically
applied to antibody treatments for the potential benefit of
patients with multiple myeloma.”
Arthur Lahr, chief executive officer of Kiadis,
added “This publication demonstrates that CD38KO K-NK cells are
resistant to killing by anti-CD38 antibodies, and demonstrates how
CD38KO K-NK cells improve potency of anti-CD38 antibodies. This
data drove Sanofi’s excitement to license KNK004 for combination
with Sarclisa®, to provide better treatment options for multiple
myeloma patients. This data showcases the scientific rationale
underpinning the collaboration with Sanofi, and should enhance the
understanding of the potential of this combination.”
A reprint of the article can be found here:
https://bit.ly/2BgEyDH
Disclosures: Dr. Lee was a
co-founder of CytoSen prior to its acquisition by Kiadis in 2019
and is currently chair of Kiadis’ scientific advisory board (SAB).
He holds stock in Kiadis, and has received financial compensation
from Kiadis for consulting, for serving on the Company’s SAB, and
for intellectual property licensed to Kiadis from Nationwide
Children’s Hospital. He may receive future income related to
successful commercialization of the technology.
Kiadis contacts
Kiadis: Maryann
Cimino, Sr. Manager, Corporate Affairs Tel: +1 (617) 710-7305
m.cimino@kiadis.com |
LifeSpring LifeSciences
Communication:Leon Melens (Amsterdam)Tel: +31 538 16
427lmelens@lifespring.nl Optimum Strategic
Communications: Mary Clark, Supriya Mathur Tel: +44 203
950 9144 kiadis@optimumcomms.com |
Dutch Translation/Nederlandse vertaling
Kiadis Pharma N.V. (‘Kiadis’),
een biofarmaceutische onderneming in de klinische fase gericht op
ontwikkeling van innovatieve Natural Killer Cell-therapieën voor
patiënten met levensbedreigende aandoeningen, maakt de publicatie
bekend van een artikel in het toonaangevende wetenschappelijke
tijdschrift Blood, Journal of the American Society of Hematology.
Het artikel beschrijft de synergetische werking van Kiadis’ K-NK004
cellen en een anti-CD38-monoklonaal antilichaam (mAb) voor een
betere doding van bloedkankercellen bij de ziekte van Kahler.
De publicatie beschrijft het gebruik van het
CRISPR/Cas9-systeem voor het verwijderen van het CD38 gen (een
zogenoemde ‘knock out’) uit ex vivo met FC21 geproduceerde
K-NK-cellen , met een knock-out efficiëntie van 82%. Normale NK
cellen worden door anti-CD38 antilichamen aangevallen en gedood,
maar deze gemodificeerde CD38KO K-NK004-cellen zijn volledig
resistent tegen dit nadelige effect van anti-CD38-antilichamen. De
CD38KO K-NK-cellen bleven veel langer beschikbaar in diermodellen,
in vergelijking met natuurlijke NK-cellen. De publicatie laat zien
dat combinatie van CD38KO K-NK004 cellen met anti-CD38 antilichaam
resulteert in verbeterde doding van tumorcellen in vergelijking met
anti-CD38 antilichaam alleen of anti-CD38 antilichaam met
natuurlijke NK cellen, bij zowel multipel myeloom-cellijnen als bij
primaire multipel myeloom-cellen. Samengevat tonen deze bevindingen
dat adoptieve immunotherapie met behulp van CD38KO K-NK004-cellen
de activiteit van anti-CD38-antilichamen bij multipel myeloom
significant kan verbeteren.
Dean Lee, MD, PhD, coauteur van het
artikel en directeur van het programma voor cellulaire therapie en
kankerimmunologie in het Nationwide Children’s Hospital en het
kankercentrum van de Ohio State University, zegt:
“Het onderzoek is het resultaat van samenwerking
met Gabriel Ghiaur, MD, PhD, coauteur van het artikel en
assistent-professor oncologie aan het Sidney Kimmel Comprehensive
Cancer Center, Johns Hopkins University. Door combinatie van de
CRISPR/Cas9-technologie met het FC21-NK-celplatform, waren we in
staat om een K-NK-celtherapie te produceren en te testen, om
immunotherapie te verbeteren tegen multipel myeloom, de ziekte van
Kahler. De eenvoud en de effectiviteit van deze aanpak brengen
toepassing in de kliniek snel dichterbij, wat kan bijdragen aan een
verbeterde standaardbehandeling van patiënten. ”
Robert Friesen, chief scientific officer
van Kiadis vult aan:
"We zijn zeer verheugd over het gepubliceerde
resultaat van deze wetenschappelijke studie die proof-of-concept
aantoont voor onze knock-out CD38 K-NK-cellen. De publicatie toont
aan dat CD38KO K-NK-cellen resistent zijn tegen doding door
anti-CD38-antilichamen en laat zien hoe CD38KO K-NK-cellen de
potentie van anti-CD38-antilichamen verbeteren. "
Arthur Lahr, chief executive officer van
Kiadis, voegde toe:
“De gegevens in deze publicaties zorgden ervoor
dat Sanofi enthousiast werd over ons K-NK004 product voor
combinatie met Sarclisa®, om behandelingsopties voor patiënten met
multipel myeloom te verbeteren. Deze studiegegevens vormden de
wetenschappelijke grondslag voor de recent gesloten afgesloten
licentie en samenwerking met Sanofi.”
Het artikel is hier te vinden:
https://bit.ly/2BgEyDH
Toelichting: Dr. Lee was een
van de oprichters van CytoSen voorafgaand aan de overname door
Kiadis in 2019 en is momenteel voorzitter van de Wetenschappelijke
Adviesraad (SAB) van Kiadis. Hij bezit aandelen in Kiadis en heeft
financiële compensatie van Kiadis ontvangen voor advies, voor zijn
zitting in de Wetenschappelijke Adviesraad van het bedrijf en voor
het aan Kiadis in licentie geven van intellectuele eigendom van
Nationwide Children’s Hospital. Mogelijk ontvangt hij toekomstige
inkomsten in verband met succesvolle commercialisering van de
technologie.
Dit persbericht vormt een vertaling van het
gepubliceerde Engelstalige persbericht. Bij eventuele verschillen
is de tekst van het Engelstalige persbericht altijd
bepalend.
About Kiadis’ K-NK-cell Based
Medicines
Kiadis’ NK-cell programs consist of
off-the-shelf and haplo donor cell-based medicines for the
treatment of liquid and solid tumors as adjunctive and stand-alone
therapies.
The Company’s NK-cell PM21 particle technology
enables improved ex vivo expansion and activation of anti-cancer
cytotoxic NK-cells supporting multiple high-dose infusions. Kiadis’
proprietary off-the-shelf NK-cell platform is based on NK-cells
from unique universal donors. The Kiadis off-the-shelf K-NK
platform can make NK-cell based product rapidly and economically
available for a broad patient population across a potentially wide
range of indications.
Kiadis is clinically developing K-NK003 for the
treatment of relapse/refractory acute myeloid leukemia. The Company
is also developing K-NK002, which is administered as an adjunctive
immunotherapeutic on top of HSCT and provides functional, mature
and potent NK-cells from a haploidentical family member. In
addition, the Company has pre-clinical programs evaluating NK-cell
based medicines for the treatment of solid tumors.
About Relapsed/Refractory Acute Myeloid
Leukemia (R/R AML)
Acute myelogenous leukemia (AML) is the most
common type of acute leukemia in adults and has the lowest survival
rate of all leukemias. AML relapse affects nearly half of all
leukemia patients who achieved remission after initial treatment
and can continue to occur several months to several years after
treatment with the majority of relapses occurring within two to
three years of the initial treatment. Patients with relapsed or
refractory leukemia have limited treatment options and poor
survival rates.
The goal of treatment for acute myeloid leukemia
(AML) is to put the leukemia into complete remission and to keep it
that way. Unlike conventional chemotherapy options, which primarily
target dividing cells, immunotherapeutic therapies aim at directing
an immune response against tumor cells. Natural Killer (NK) cells
are effector lymphocytes of the innate immune system capable of
exerting anti-AML activity. The K-NK cell platform is a cell-based
immunotherapy to treat patients with advanced blood cancer.
About Kiadis
Founded in 1997, Kiadis is building a fully
integrated biopharmaceutical company committed to developing
innovative cell-based medicines for patients with life-threatening
diseases. With headquarters in Amsterdam, The Netherlands, and
activities across the United States, Kiadis is reimagining medicine
by leveraging the natural strengths of humanity and our collective
immune system to source the best cells for life.
Kiadis is listed on the regulated market of
Euronext Amsterdam and Euronext Brussels since July 2, 2015, under
the symbol KDS. Learn more at www.kiadis.com.
Forward Looking Statements
Certain statements, beliefs and opinions in this
press release are forward-looking, which reflect Kiadis’ or, as
appropriate, Kiadis’ officers’ current expectations and projections
about future events. By their nature, forward-looking statements
involve a number of known and unknown risks, uncertainties and
assumptions that could cause actual results, performance,
achievements or events to differ materially from those expressed,
anticipated or implied by the forward-looking statements. These
risks, uncertainties and assumptions could adversely affect the
outcome and financial effects of the plans and events described
herein. A multitude of factors including, but not limited to,
changes in demand, regulation, competition and technology, can
cause actual events, performance, achievements or results to differ
significantly from any anticipated or implied development.
Forward-looking statements contained in this press release
regarding past trends or activities should not be taken as a
representation that such trends or activities will continue in the
future. As a result, Kiadis expressly disclaims any obligation or
undertaking to release any update or revisions to any
forward-looking statements in this press release as a result of any
change in expectations or projections, or any change in events,
conditions, assumptions or circumstances on which these
forward-looking statements are based. Neither Kiadis nor its
advisers or representatives nor any of its subsidiary undertakings
or any such person’s officers or employees guarantees that the
assumptions underlying such forward-looking statements are free
from errors nor does either accept any responsibility for the
future accuracy of the forward-looking statements contained in this
press release or the actual occurrence of the anticipated or
implied developments. You should not place undue reliance on
forward-looking statements, which speak only as of the date of this
press release.