Categories: News

Kiadis announces new data at the 2020 ASH Annual Meeting and Exposition

~Five presentations related to Kiadis’ K-NK cell therapy platform will be presented

at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition~

  • An oral presentation (abstract #68) presents data that show multiple infusions of FC21-NK cells in patients with relapsed and refractory acute myeloid leukemia (R/R AML) yielded impressive outcomes with no infusion reactions or toxicities
  •  A poster presentation (abstract #825) describes data demonstrating NKTR-255 significantly enhanced the ADCC of expanded NK cells with anti-CD20 type I and type II antibodies against CLL, FL and rituximab-resistant BL cells
  • A poster presentation (abstract #2151) provides details of a phase I pilot study in CML patients to evaluate safety and examine if adding K-NK003 to ongoing Tyrosine kinase inhibitors (TKI) therapy leads to achieving MRD negative status
  • A poster presentation (abstract #2341) provides the details of the ongoing phase II trial, NK-REALM, investigating the safety and efficacy of K-NK002 for the treatment of patients with high-risk AML or MDS undergoing haploidentical bone marrow transplantation
  • A poster presentation (abstract #2347) describes the phase I study testing the safety of FC21-expanded, off-the-shelf NK cells for treatment of R/R AML and MDS

Amsterdam, The Netherlands, December 6, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical-stage biopharmaceutical company developing innovative NK-cell-based medicines for the treatment of life-threatening diseases, announces that new data related to its K-NK cell therapy platform will be presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition being held virtually from December 5-8, 2020. Abstract #68 is an oral presentation with data showing that multiple infusions of ex vivo expanded haploidentical NK cells in R/R AML patients yielded unprecedented outcomes with no safety reactions or toxicities. The poster for abstract #825 presents data that demonstrate NKTR-255 significantly enhanced the ADCC of expanded NK cells with anti-CD20 type I and type II antibodies against Chronic Lymphocytic Leukemia (CLL), Follicular Lymphoma (FL), and rituximab-resistant BL cells. Three additional posters, abstracts #2151, #2341, and #2347, provide details of ongoing studies within the K-NK cell therapy programs.

The ASH abstracts are now available at https://ash.confex.com/ash/2020/webprogram/start.html

Details of the oral presentation are as follows:

Oral Presentation (#68) Title: Haploidentical MbIL-21 Ex Vivo Expanded NK Cells (FC21-NK) for Patients with Multiple Relapsed and Refractory Acute Myeloid Leukemia

Although allogeneic stem-cell transplantation remains the only curative treatment for patients with advanced acute myeloid leukemia (AML), only a minority of these patients achieve disease control prior to their transplant. Natural killer (NK) cells have potent anti-leukemic activity but are functionally deficient in AML. Adoptive NK-cell therapy using high-doses of functionally active NK-cells could overcome these limitations.

Kiadis’ FC21 platform uses K562 feeder cells that express membrane bound IL-21 and 41BB ligand to generate FC21-NK cells that are hyperfunctional in phenotype and function with therapeutic potential. This phase I clinical trial assessed the safety, feasibility and maximum tolerated dose (MTD) of haploidentical FC21-NK cells for patients with R/R AML. In this study, 12 patients with relapsed/refractory AML who averaged five previous therapies received FC21-NK cells. Haploidentical donors were selected based on KIR characteristics, when multiple donors were available, and the donor NK cells were expanded over three weeks and cryopreserved. Three dose levels between 106-108 cells/kg were planned and patients received cytoreductive chemotherapy with fludarabine, cytarabine and G-CSF. After chemotherapy, patients received NK cell infusions three times per week with up to six infusions.

Multiple infusions of FC21-NK cells yielded impressive outcomes with eight patients (66.7%) achieving CR/CRi at 30 days post-NK cell infusion with no infusion related toxicity or cytokine release syndrome observed. Seven patients had absolute neutrophil count recovery at 60 days. Five patients proceeded to haploidentical stem-cell transplant from the same donor and were transplanted in CR/CRi. Median overall survival and disease-free survival were 17.6 and 3.3 months and 28 and 20 months for the whole cohort and the patients receiving transplant, respectively. Responses were observed irrespective of dose and FC21-NK cells were shown to persist for at least five weeks after infusion.

In addition to the oral presentation, there will be four poster presentations. Details of the poster presentations are as follows:

Poster Presentation (#825) Title: Optimizing Ex-vivo Expanded NK Cell- Mediated Antibody-Dependent Cellular Cytotoxicity (ADCC) Combined With NKTR-255 in Chronic Lymphocytic Leukemia (CLL), Follicular Lymphoma (FL), and Burkitt Lymphoma (BL)

In this study, the effects of NKTR-255 on the ADCC of expanded NK cells with anti-CD20 type I and type II antibodies against CLL, FL and rituximab-resistant BL were investigated. The data presented show NKTR-255 significantly enhanced the ADCC of expanded NK cells with anti-CD20 type I and type II antibodies against CLL, FL and rituximab-resistant BL cells in vitro with enhanced IFN-g, granzyme B and perforin release. NKTR-255 also significantly enhanced granzyme and perforin release from expanded NK cells when combined with rituximab against MEC-1. Additionally, NKTR-255 significantly enhanced the in vitro cytotoxicity of expanded NK cells when combined with obinutuzumab against rituximab-resistant BL cells and also significantly enhanced IFN-g, granzyme and perforin release from expanded NK cells when combined with obinutuzumab against Raji-2R.

Poster Presentation (#2151) Title: A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy

This open label, non-randomized, prospective phase I pilot study will evaluate safety and examine whether the addition of K-NK003 to ongoing Tyrosine kinase inhibitors (TKI) therapy for CML patients with persistent molecular residual disease (MRD) enables patients to achieve MRD negative status. Patients will be treated with K-NK003 on day one of each 14-day cycle, for a total of six cycles, in conjunction with their ongoing TKI therapy. The primary endpoint is safety. The efficacy objective is to estimate the rate of optimal molecular responses (negative to at least MR4.5). Secondary and exploratory endpoints include the proportion of patients with a reduction in BCR-ABL transcripts and NK cell number and function.

Poster Presentation (#2341) Title: BMT CTN 1803: Haploidentical Natural Killer Cells (K-NK002) to Prevent Post-Transplant Relapse in AML and MDS (NK-REALM)

In this phase II, open-label, multicenter trial, (NCT04395092), the safety and efficacy of K-NK002 for the treatment of patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing haplo bone marrow transplantation (BMT) will be investigated. An initial six patient safety run-in phase (1×107 cells/kg) will precede enrollment into the full study of approximately 60 patients at the recommended phase II dose of (1×108 cells/kg). Three doses of K-NK002 will be administered by IV on Days -2, +7, and +28, relative to the haploBMT. For this study, the primary endpoint is cumulative incidence of relapse at one year post haploBMT in patients receiving at least one infusion of K-NK002. There are several secondary endpoints including safety and tolerability; overall survival; non-relapse mortality; relapse-free survival; GVHD-free survival; cumulative incidence of acute GVHD and chronic GVHD and overall incidence of toxicity.

Poster Presentation (#2347) Title: A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-Shelf, Third-Party Natural Killer Cells for Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

This phase I study, (NCT04220684), is designed to investigate the safety of FC21-expanded, Off-the-shelf (OTS) NK cells for treatment of patients with primary refractory or relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Patients aged ≥18 or ≤80 years are enrolled into two cohorts with patients under 60 years of age and able to tolerate intensive chemo and sensitive to Cytarabine receiving fludarabine and cytarabine and patients older than 60 years of age either unable or unwilling to tolerate intensive chemo or disease insensitive to cytarabine receiving fludarabine and decitabine. All patients subsequently receive a total of six infusions of NK cells administered thrice weekly for two weeks (between day 0-21). Three NK cell dose-levels: 1×107, 3×107 & 1×108 cells/kg/dose will be explored to determine the maximum tolerated dose. Primary objectives are to determine the recommended phase II dose and overall response rate (CR, CRi & MLFS). Secondary objectives will explore PFS, OS & MRD negativity, cell counts, infectious complications, and patients proceeding to transplant. Of the six patients treated to date, no infusion related reactions, neurotoxicity, cytokine release syndrome or forms of GVHD were observed. In addition, NK cells were shown to persist up to day 56. Enrollment in both cohorts is ongoing.

Dutch Translation/Nederlandse vertaling

Kiadis Pharma N.V. (‘Kiadis’) is een biofarmaceutisch bedrijf in de klinische fase dat innovatieve op NK-cellen gebaseerde geneesmiddelen ontwikkelt voor de behandeling van levensbedreigende ziekten, maakt bekend dat nieuwe gegevens met betrekking tot het K-NK-celtherapieplatform zullen worden gepresenteerd op de 62e American Society of Hematology (ASH) Annual Meeting and Exposition, die virtueel wordt gehouden van 5 tot 8 december 2020. Abstract #68 is een mondelinge presentatie van data waaruit blijkt dat meerdere infusies van ex vivo geëxpandeerde haplo-identieke NK-cellen bij R/R AML-patiënten niet eerder getoonde resultaten opleverden zonder reacties of toxiciteiten. De poster voor abstract #825 betreft de presentatie van data die aantonen dat NKTR-255 de ADCC van geëxpandeerde NK-cellen significant verbeterde met anti-CD20 type I en type II antilichamen tegen chronische lymfatische leukemie (CLL), folliculair lymfoom (FL) en rituximab-resistente BL cellen. Drie overige posters, abstracts #2151, #2341 en #2347, geven details over lopende onderzoeken binnen de K-NK-celtherapieprogramma’s.

De ASH abstracts zijn thans beschikbaar op https://ash.confex.com/ash/2020/webprogram/start.html

Details van de mondelinge presentatie:

Mondelinge presentatie (#68) Titel: Haplo-identieke MbIL-21 ex vivo geëxpandeerde NK-cellen (FC21-NK) voor patiënten met meerdere recidiverende en refractaire acute myeloïde leukemie (R/R AML)

Hoewel allogene stamceltransplantatie de enige genezende behandeling blijft voor patiënten met gevorderde acute myeloïde leukemie (AML), bereikt slechts een minderheid van deze patiënten voorafgaand aan hun transplantatie ziektecontrole. Natural Killer (NK)-cellen hebben een krachtige anti-leukemische werking, maar zijn functioneel deficiënt bij AML. Adoptieve NK-celtherapie met hoge doses functioneel actieve NK-cellen zou deze beperkingen kunnen overwinnen.

Het FC21-platform van Kiadis gebruikt K562-feedercellen die membraangebonden IL-21- en 41BB-ligand tot expressie brengen om FC21-NK-cellen te genereren die hyperfunctioneel zijn in fenotype en functioneren met therapeutisch potentieel. Deze fase I klinische studie evalueerde de veiligheid, haalbaarheid en maximaal getolereerde dosis (MTD) van haplo-identieke FC21-NK-cellen voor patiënten met R/R AML. In dit onderzoek kregen 12 patiënten met R/R AML, die gemiddeld vijf eerdere therapieën hadden ondergaan, FC21-NK-cellen. Haplo-identieke donoren werden geselecteerd op basis van KIR-kenmerken, wanneer er meerdere donoren beschikbaar waren. De donor-NK-cellen werden gedurende drie weken opgewerkt en gecryopreserveerd. Er waren drie dosisniveaus tussen 106 -108  cellen/kg gepland en patiënten kregen cytoreductieve chemotherapie met fludarabine, cytarabine en G-CSF. Na chemotherapie kregen patiënten driemaal per week NK-cel-infusies met maximaal zes infusies.

Meerdere infusies van FC21-NK-cellen leverden indrukwekkende resultaten op waarbij acht patiënten (66,7%) CR/CRi bereikten 30 dagen na NK-cel-infusie zonder dat er infusie-gerelateerde toxiciteit of cytokine-afgiftesyndroom werd waargenomen. Zeven patiënten hadden een herstel van het absolute aantal neutrofielen na 60 dagen. Vijf patiënten gingen over tot een haplo-identieke stamceltransplantatie van dezelfde donor en werden getransplanteerd in CR/CRi. De mediane totale overleving en ziektevrije overleving waren 17,6 en 3,3 maanden en 28 en 20 maanden voor respectievelijk alle patienten en de patiënten die een transplantatie kregen. Reacties werden ongeacht de dosis waargenomen en FC21-NK-cellen bleven gedurende ten minste vijf weken na infusie aanwezig.

Naast de mondelinge presentatie zijn er vier posterpresentaties. Details van de posterpresentaties zijn als volgt:

Posterpresentatie (#825) Titel: Optimalisatie van ex-vivo geëxpandeerde NK-cel-gemedieerde antilichaamafhankelijke cellulaire cytotoxiciteit (ADCC) gecombineerd met NKTR-255 bij chronische lymfatische leukemie (CLL), folliculair lymfoom (FL) en Burkitt lymfoom (BL)

In deze studie werden de effecten van NKTR-255 op de ADCC van geëxpandeerde NK-cellen met anti-CD20 type I en type II antilichamen tegen CLL, FL en rituximab-resistente BL onderzocht. De gepresenteerde gegevens laten zien dat NKTR-255 de ADCC van geëxpandeerde NK-cellen significant verbeterde met anti-CD20 type I en type II antilichamen tegen CLL, FL en rituximab-resistente BL-cellen in vitro met verbeterde IFN-g, granzyme B en perforine-afgifte. NKTR-255 verbeterde ook significant de afgifte van granzyme en perforine uit geëxpandeerde NK-cellen in combinatie met rituximab tegen MEC-1. Bovendien verhoogde NKTR-255 significant de in-vitro-cytotoxiciteit van geëxpandeerde NK-cellen in combinatie met obinutuzumab tegen rituximab-resistente BL-cellen en verbeterde het ook significant de afgifte van IFN-g, granzyme en perforine uit geëxpandeerde NK-cellen in combinatie met obinutuzumab tegen Raji-2R.

Posterpresentatie (#2151) Titel: een fase I-onderzoek naar het gebruik van Natural Killer-cellen (K-NK) voor patiënten met chronische myeloïde leukemie (CML) en moleculaire restziekte (MRD) na therapie met tyrosine-kinaseremmers (TKI)

Deze open-label, niet-gerandomiseerde, prospectieve fase I-pilotstudie zal de veiligheid evalueren en onderzoeken of de toevoeging van K-NK003 aan een lopende therapie met tyrosine-kinaseremmers (TKI) voor CML-patiënten met persisterende moleculaire restziekte (MRD) patiënten in staat stelt een negatieve MRD-status te bereiken. Patiënten zullen worden behandeld met K-NK003 op dag één van elke cyclus van 14 dagen, gedurende in totaal zes cycli, in combinatie met hun lopende TKI-therapie. Het primaire eindpunt is veiligheid. Voor wat betreft werkzaamheid is het doel om de snelheid van optimale moleculaire responsen in te schatten (negatief tot minimaal MR4.5). Secundaire en exploratoire eindpunten omvatten het aantal patiënten met een vermindering van BCR-ABL-transcripten en NK-cel-aantal en -functie.

Posterpresentatie (#2341) Titel: BMT CTN 1803: Haplo-identieke Natural Killer Cellen (K-NK002) ter voorkoming van terugval na transplantatie bij AML en MDS (NK-REALM)

In deze fase II, open-label, multicenter-studie (NCT04395092), worden de veiligheid en werkzaamheid van K-NK002 voor de behandeling van patiënten met hoog-risico acute myeloïde leukemie (AML) of myelodysplastisch syndroom (MDS) die een haplo-beenmergtransplantatie ondergaan (BMT) onderzocht. Een eerste veiligheidsfase in zes patiënten (1×107  cellen/kg) zal voorafgaan aan de start van het volledige onderzoek in ongeveer 60 patiënten met de aanbevolen fase II-dosis van (1 × 108  cellen / kg). Drie doses K-NK002 zullen intraveneus worden toegediend op dagen -2, +7 en +28, ten opzichte van de haploBMT. Voor deze studie is het primaire eindpunt de cumulatieve incidentie van terugkeer van de ziekte (relapse) één jaar na haploBMT bij patiënten die ten minste één infusie van K-NK002 kregen. Er zijn verschillende secundaire eindpunten, waaronder veiligheid en verdraagbaarheid; algemeen overleven; sterfte zonder terugval; ziekte-vrije overleving; GVHD-vrije overleving; cumulatieve incidentie van acute GVHD en chronische GVHD en algehele incidentie van toxiciteit.

Posterpresentatie (#2347) Titel: een fase I klinisch onderzoek naar de veiligheid van IL-21-uitgebreide, ‘off-the-shelf’ natural killercellen van derden voor recidiverende/refractaire acute myeloïde leukemie en myelodysplastisch syndroom

Deze fase I-studie (NCT04220684) is bedoeld om de veiligheid van FC21-geëxpandeerde, off-the-shelf (OTS) NK-cellen te onderzoeken voor de behandeling van patiënten met primaire refractaire of recidiverende acute myeloïde leukemie (AML) of myelodysplastisch syndroom (MDS). Patiënten van ≥18 of ≤80 jaar worden geïncludeerd in twee cohorten: patiënten jonger dan 60 jaar die intensieve chemotherapie kunnen verdragen en gevoelig zijn voor Cytarabine, die fludarabine en cytarabine krijgen; en patiënten ouder dan 60 jaar die geen intensieve chemotherapie kunnen of willen verdragen of ziekte ongevoelig voor cytarabine, die fludarabine en decitabine krijgen. Alle patiënten ontvangen vervolgens in totaal zes infusies van NK-cellen die driemaal per week worden toegediend gedurende twee weken (tussen dag 0-21). Drie NK-celdosisniveaus: 1×107, 3×107  & 1×108  cellen/kg/dosis zullen worden onderzocht om de maximaal getolereerde dosis te bepalen. Primaire doelstellingen zijn het bepalen van de aanbevolen fase II-dosis en het algehele responspercentage (CR, CRi en MLFS). Secundaire doelstellingen zullen PFS, OS & MRD-negativiteit, celaantallen, infectieuze complicaties en patiënten die overgaan tot transplantatie betreffen. Van de zes tot nu toe behandelde patiënten werden geen infusie-gerelateerde reacties, neurotoxiciteit, cytokine-release-syndroom of vormen van GVHD waargenomen. Bovendien bleken NK-cellen te persisteren tot dag 56. Recrutering in beide cohorten is aan de gang.

Dit persbericht vormt een samenvatting van het gepubliceerde Engelstalige persbericht. Bij eventuele verschillen is de tekst van het Engelstalige persbericht altijd leidend.

Contacts

Kiadis:
Maryann Cimino, Sr. Manager, Corporate Affairs
Tel: +1 (617) 710-7305
m.cimino@kiadis.com

 

LifeSpring Life Sciences Communication:
Leon Melens (Amsterdam)
Tel: +31 (20) 538 16 427
lmelens@lifespring.nl

Optimum Strategic Communications:
Mary Clark, Supriya Mathur
Tel: +44 (203) 950 9144
kiadis@optimumcomms.com

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 and infectious diseases. 
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. Furthermore, Kiadis is developing K-NK-ID101 for the treatment of Covid-19. In addition, the Company has pre-clinical programs evaluating NK-cell based medicines for the treatment of solid tumors and infectious diseases.

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 offices 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.

Staff

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