Kiadis announces publication in Blood highlighting proof-of-concept to enhance potency of anti-CD38 antibodies with Kiadis’ K-NK004, recently licensed by Sanofi

CD38^KO 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 (CD38^KO) in ex vivo expanded peripheral blood K-NK cells, with 82% knock out efficiency. These CD38^KO K-NK cells were completely resistant to anti-CD38 antibody-induced fratricide. In addition, as compared to wild type NK cells, the CD38^KO 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 CD38^KO 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 CD38^KO 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 CD38^KO K-NK cells are resistant to killing by anti-CD38 antibodies, and demonstrates how CD38^KO 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.

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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 CD38^KO K-NK004-cellen zijn volledig resistent tegen dit nadelige effect van anti-CD38-antilichamen. De CD38^KO K-NK-cellen bleven veel langer beschikbaar in diermodellen, in vergelijking met natuurlijke NK-cellen. De publicatie laat zien dat combinatie van CD38^KO 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 CD38^KO 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 CD38^KO K-NK-cellen resistent zijn tegen doding door anti-CD38-antilichamen en laat zien hoe CD38^KO 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.