Press Release

Kiadis announces new data demonstrating that K-NK cells persist and proliferate in vivo and that K-NK cells used across past and future trials have the same unique hyperfunctional phenotype

June 12, 2020 at 2:30 AM EDT
  • 3 presentations related to Kiadis’ K-NK cell therapy platform will be presented today at the 25th Congress of the European Hematology Association
  1. An oral presentation (abstract #S284) shows clinical data that K-NK cells persist and proliferate in vivo
  2. A poster presentation (abstract #EP1487) presents data that demonstrate uniformity of K-NK cells expanded with FC21 (as used in past clinical trials) or PM21 (industrial platform to be used in future clinical trials including NK-REALM), which are distinct from non-expanded NK cells in phenotype and are highly cytotoxic, with elevated secretion of cytokines
  3. An additional poster presentation (abstract #EP585) describes data from a phase I study of infusions of K-NK cells expanded ex vivo with FC21 following chemotherapy that show evidence of anti-microbial activity in patients with relapsed or refractory acute myeloid leukemia (R/R AML)

Amsterdam, The Netherlands, June 12, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company, announces that new data related to its K-NK cell therapy platform will be presented today at the virtual edition of the 25th European Hematology Association (EHA) Congress. Abstract #S284 is an oral presentation that shows clinical data from several phase I/II studies demonstrating that ex vivo expanded K-NK cells persist and proliferate in vivo for up to five weeks. The poster for abstract EP1487 presents data that demonstrate K-NK cells expanded with FC21 or PM21 are distinct from non-expanded NK cells in phenotype and gene expression signature and are highly cytotoxic, with elevated levels of cytokines. Finally, a poster (abstract #EP585) describes positive clinical outcomes in a subset of R/R AML patients treated with K-NK cells expanded with FC21 following chemotherapy that were enrolled in a phase I/II study with concomitant infections.

The EHA abstracts are now available at www.ehaweb.org. Details of the presentations are as follows:

Abstract #S284: Early-phase Clinical Trials of Adoptive Transfer of Hyperfunctional NK Cells Expanded Ex Vivo with IL-21 Demonstrate Functional, Phenotypic, and Haplotype-specific evidence of in vivo persistence

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. FC21-NK cells were administered to 59 patients in three clinical settings: allogeneic (haploidentical) FC21-NK cells in combination with haploidentical hematopoietic stem cell transplant (haplo-HSCT) for the treatment of high risk hematological malignancies, allogeneic FC21-NK cells administered after chemotherapy for the treatment of relapsed or refractory AML, and autologous FC21-NK cells administered for the treatment of patients with high-grade gliomas.

Persistence and in vivo proliferation of adoptively-transferred therapeutic lymphocytes have been closely correlated with clinical responses. The presence of haploidentical donor NK cells at day 7 after adoptive transfer is a surrogate marker of expansion and persistence associated with response.

FC21-NK cell persistence and proliferation was evaluated in 33 of 59 patients. In the context of allogenic FC21-NK cells administered in the haplo-HSCT setting, FC21-NK cells proliferate in vivo and persist up to three weeks after infusion. In the R/R AML setting, allogenic FC21-NK cells proliferate in vivo and persist up to five weeks post infusion. Lastly, autologous FC21-NK cells administered intratumorally in patients with high-grade gliomas persist and increase to a 10-fold accumulation in the cerebral spinal fluid over eight weeks of treatment period.

The data presented show that allogeneic FC21-NK cells can persist and proliferate in vivo up to five weeks without the support of exogenous cytokines.  

Dean Lee, MD, PhD, the senior author on this abstract as well as the following abstract, 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, “The data presented today further support that FC21-NK cells display a unique phenotype and hyperfunctional activity that have significant and clinically meaningful numeric proliferation, expansion, and functional persistence after adoptive transfer.”

Abstract #EP1487: Deep Characterization of MBIL21 Ex Vivo-expanded NK Cells Using Mass Cytometry and Functional Assays, Establishes Product Consistency Across Different Manufacturing Sites and Systems

Kiadis’ FC21 platform uses K562 feeder cells that express membrane bound IL-21 and 41BB ligand to generate NK cells that are hyperfunctional in phenotype and function with therapeutic potential. Over 300 doses of NK cells up to 108/kg/dose expanded with FC21 have been delivered to over fifty patients, without any major toxicities. The manufacturing process was improved through the development of a non-cellular membrane-particle preparation (PM21) to enhance safety, efficiency, scale, and product uniformity for commercialization, and scaled up to GMP, while still providing the same stimulus for expansion and activation as FC21. The expanded NK cell product from each of these expansion platforms was analyzed and compared to NK cells freshly-isolated from peripheral blood. Samples were cryopreserved and thawed before analysis. The GMP scale FC21-NK and PM21-NK samples analyzed included drug product as intended for use in past and future clinical trials.

The data presented show expanded NK cells with similar phenotype and functionality regardless of the expansion method used, whether with pre-clinical scale FC21, GMP scale FC21, or GMP scale PM21. NK cells expanded with FC21 or PM21 have a uniformly distinct signature from non-expanded (primary) NK cells, have high viability and are highly cytotoxic with unique cytokine profiles, after a freeze and thaw cycle.  

The similarity between the NK cells GMP produced for the past phase I/II HSCT trial and for the recently FDA approved phase II HSCT NK-REALM trial provide a bridge between studies and for future studies delivering PM21-NK cells.

Dr. Lee commented, “The data on this poster show that we are able to generate large numbers of highly active NK cells expanded with FC21 and PM21 using different manufacturing processes, different feeder cells, and different forms of the activator that result in cells that are functionally and phenotypically indistinguishable. This will allow for uniformity and potency across productions sites and platforms used in ongoing and future clinical trials.”

Abstract #EP585: Clinical and Radiologic Resolution of Infections During Treatment with MBIL-21-expanded CD56Bright/CD16Bright NK Cells in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)

In a phase I study (NCT02809092), multiple doses of NK cells expanded with FC21 were infused following standard fludarabine, cytarabine, and granulocyte-colony stimulating factor (FLAG) induction in patients with R/R AML. The objective of this analysis was to investigate preliminary safety and efficacy data in a subgroup of patients with R/R AML and concurrent severe infectious complications from this phase I study. Of 13 patients with R/R AML enrolled and treated in the study, three had concomitant infections or high-risk bacterial colonization and were included in this analysis.

The data presented show that two out of the three patients with serious concomitant infections demonstrated complete responses (CR) lasting 151 and 269 days after receiving FC21-NK infusions. Furthermore, both patients had complete resolution of infection and pulmonary symptoms while the third patient experienced significant clinical improvement with almost complete resolution of cholangitis. Multiple IV infusions of FC21-NK cells administered to patients with serious infectious complications were well tolerated and encouraging signs of antitumor and antimicrobial activity were observed.

Lucia Silla, MD, PhD, at Hospital de Clínicas de Porto Alegre (HCPA) commented, “This phase I study shows promising results that treatment with MBIL-21-expanded FC21-NK cells might be a possible alternative treatment that offers a less toxic regimen for patients with serious infectious complications who have completed chemotherapy and are frail with AML.”

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

 
Optimum Strategic Communications:
Mary Clark, Supriya Mathur
Tel: +44 203 950 9144
David Brilleslijper (Amsterdam)
Tel: +31 610 942 514
kiadis@optimumcomms.com

Dutch Translation/Nederlandse vertaling

Kiadis Pharma nv ('Kiadis') (Euronext Amsterdam en Brussel: KDS), een biofarmaceutisch bedrijf gericht op onderzoek in de klinische fase, zal vandaag op de digitale editie van het 25e congres van de European Hematology Association (EHA) nieuwe informatie over het K-NK-celtherapieplatform presenteren. Abstract #S284 is een mondelinge presentatie met klinische gegevens uit verschillende fase I-/II-onderzoeken die aantonen dat ex vivo geëxpandeerde K-NK-cellen tot maximaal vijf weken in vivo circuleren en verder expanderen. De poster voor abstract EP1487 toont gegevens waaruit blijkt dat met FC21 en PM21 geëxpandeerde K-NK-cellen zoals gebruikt in eerdere en toekomstige klinische studies een identiek fenotype en andere genexpressiekenmerken hebben. De gegevens tonen aan dat FC21-NK en PM21-NK anders zijn dan niet-geëxpandeerde NK-cellen, zeer cytotoxisch zijn en hogere niveaus cytokine produceren. Ten slotte worden met een poster (abstract #EP585) positieve klinische resultaten beschreven van een subgroep van R/R AML-patiënten in een fase I/II-onderzoek met gelijktijdige infecties. De patiënten werden behandeld met K-NK-cellen die met FC21 zijn geëxpandeerd na chemotherapie.

De EHA-abstracten zijn nu beschikbaar op www.ehaweb.org. Hier volgen nadere gegevens van de presentaties:

Abstract #S284: Klinische studies in een vroege fase over de adoptieve overdracht van hyperfunctionele NK-cellen die ex vivo zijn geëxpandeerd met IL-21 tonen aan dat er functionele, fenotypische en haplotypespecifieke bewijzen zijn van in-vivopersistentie.

Het FC21-platform van Kiadis gebruikt K562-feedercellen die membraangebonden IL-21- en 41BB-ligand presenteren om FC21-NK-cellen te genereren met een hyperfunctioneel fenotype en therapeutisch potentieel. Er werden in drie klinische omgevingen FC21-NK cellen toegediend aan 59 patiënten: allogene (haplo-identieke) FC21-NK-cellen in combinatie met haplo-identieke hematopoëtische stamceltransplantatie (haplo-HSCT) voor de behandeling van hoog risico hematologische maligniteiten, allogene FC21-NK-cellen die werden toegediend na chemotherapie voor de behandeling van recidiverende of refractaire AML, en autologe FC21-NK-cellen die werden toegediend aan patiënten met een hoog risico glioom.

Persistentie en in-vivogroei van adoptief overgedragen therapeutische lymfocyten zijn nauw gecorreleerd met klinische responsen. De aanwezigheid van haplo-identieke NK-donorcellen op de 7e dag na de adoptieve overdracht is een surrogaatmarker voor expansie en met respons geassocieerde persistentie.

De persistentie en groei van FC21-NK-cellen werden bij 33 van de 59 patiënten geëvalueerd. In de context van allogene FC21-NK-cellen die werden toegediend in de haplo-HSCT-omgeving, blijven FC21-NK-cellen in vivo tot drie weken na de infusie aanwezig en doorgroeien. In de R/R AML-omgeving blijven de allogene FC21-NK-cellen in vivo tot vijf weken na de infusie aanwezig en doorgroeien. Autologe FC21-NK-cellen die intratumoraal werden toegediend bij patiënten met een hoog risico glioom vertonen een tienvoudige accumulatie in het hersenvocht gedurende een behandelingsperiode van acht weken.

Uit de gepresenteerde gegevens blijkt dat allogene FC21-NK-cellen in vivo tot vijf weken aanwezig kunnen blijven en doorgroeien zonder de ondersteuning van exogene cytokines.

Dean Lee, MD, PhD, de senior auteur van dit en het volgende abstract en hoogleraar kindergeneeskunde bij het Nationwide Children's Hospital zei: "De vandaag gepresenteerde gegevens leveren verder bewijs dat FC21-NK-cellen een uniek fenotype en hyperfunctionele activiteit vertonen met significante en klinisch betekenisvolle numerieke groei, expansie en functionele persistentie na infusie."

Abstract #EP1487: Diepgaande karakterisering van MBIL21 ex vivo geëxpandeerde NK-cellen met massacytometrie en functionele tests zorgt voor consistentie van het product in verschillende productiesites en -systemen

Het FC21-platform van Kiadis gebruikt K562-feedercellen die membraangebonden IL-21- en 41BB-ligand presenteren om NK-cellen te genereren met een hyperfunctioneel fenotype en therapeutisch potentieel. Meer dan 300 doses NK-cellen tot 108/kg/dosis geëxpandeerd met FC21 werden toegediend aan meer dan vijftig patiënten, zonder ernstige toxiciteiten. Het productieproces werd verbeterd door de ontwikkeling van een preparaat van niet-cellulaire membraandeeltjes (PM21) ter verbetering van de veiligheid, efficiëntie, schaal en productuniformiteit voor commercialisering. Daarnaast werd het proces opgeschaald naar GMP, waarbij dezelfde stimulans voor expansie en activering als bij FC21 werd behouden. Het geëxpandeerde NK-celproduct van elk van deze expansieplatforms werd geanalyseerd en vergeleken met NK-cellen die direct uit perifeer bloed werden geïsoleerd. . De analyzes zijn uitgevoerd met ingevroren en weer ontdooit product dat geproduceerd was met productieprocess zoals dat gebruikt in historisch en toekomstige klinische studies.

De gepresenteerde gegevens tonen geëxpandeerde NK-cellen met een vergelijkbaar fenotype en vergelijkbare functionaliteit ongeacht de gebruikte expansiemethode, zoals preklinische schaal FC21, GMP-schaal FC21 of GMP-schaal PM21. NK-cellen die zijn geëxpandeerd met FC21 of PM21 hebben een uniform kenmerk dat anders is dan niet-geëxpandeerde (primaire) NK-cellen en hebben na invriezing en ontdooing een hoge viability, zijn zeer cytotoxisch, en hebben unieke hoge expressie van cytokines.

De overeenkomst tussen de K-NK-cellen die GMP zijn geproduceerd voor het vorige fase I-/II-HSCT-onderzoek en geproduceerd gaan worden voor de onlangs door het FDA goedgekeurde fase II-HSCT NK-REALM-onderzoek slaat een brug tussen de resultaten uit het verleden en de toekomstige onderzoeken met K-NK-cellen.

Dr. Lee merkte op: "De gegevens op deze poster tonen aan dat we grote aantallen zeer actieve met FC21 en PM21 geëxpandeerde NK-cellen kunnen genereren met verschillende productieprocessen, feedercellen en activatorvormen, waardoor de cellen wat betreft functie en fenotype niet van elkaar te onderscheiden zijn. Dit maakt uniformiteit en potentieel mogelijk tussen productielocaties en platformen die gebruikt worden in lopende en toekomstige klinische studies."

Abstract #EP585: Klinische en radiologische genezing van infecties tijdens behandeling met MBIL-21 geëxpandeerde CD56Bright/CD16Bright-NK-cellen bij patiënten met recidiverende of refractaire acute myeloïde leukemie (R/R AML)

In een fase I-onderzoek (NCT02809092) werden meerdere doses van met FC21 geëxpandeerde NK-cellen toegediend na standaardinductie van fludarabine, cytarabine en granulocyt-koloniestimulerende factor (FLAG) bij patiënten met R/R AML. Het doel van deze analyse was om de voorlopige resultaten met FC21-NK cellen te onderzoeken in een subgroep van patiënten met ernstige infectieuze complicaties . Van de 13 patiënten met R/R AML die in de studie werden opgenomen en behandeld, hadden er drie gelijktijdig een infectie of een hoog risico op bacteriële kolonisatie.

Uit de gepresenteerde gegevens blijkt dat twee van de drie patiënten met een ernstige gelijktijdige infectie complete responsen (CR) vertoonden gedurende 151 en 269 dagen na toediening van FC21-NK-infusies. Bovendien verdwenen de infectie- en longziektesymptomen bij beide patiënten volledig, terwijl bij de derde patiënt een significante klinische verbetering optrad met bijna volledige genezing van cholangitis. De verschillende IV-infusies van FC21-NK-cellen die aan patiënten met ernstige infectieuze complicaties werden toegediend, werden goed verdragen.

Lucia Silla, MD, PhD, bij Hospital de Clínicas de Porto Alegre (HCPA) zei: "De resultaten van dit fase I-onderzoek zijn veelbelovend en tonen aan dat behandeling met MBIL-21 geëxpandeerde FC21-NK-cellen een behandeling kan zijn voor zwakke patiënten met AML die chemotherapie hebben ondergaan en ernstige infectieuze complicaties hebben."

Openbaarmakingen: Dr. Lee was medeoprichter van CytoSen vóór de overname door Kiadis in 2019 en is momenteel voorzitter van de wetenschappelijke adviesraad (SAB) van Kiadis. Hij heeft aandelen in Kiadis en heeft van Kiadis een financiële vergoeding ontvangen voor consulting, voor zijn werk voor de adviesraad van het bedrijf en voor intellectuele eigendom die door NCH gelicentieerd werd aan Kiadis. Hij kan toekomstige inkomsten ontvangen in verband met de 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 Therapies
Kiadis’ NK-cell programs consist of off-the-shelf and haplo donor cell therapy products 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 therapy 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 therapy for the treatment of solid tumors. 

About Kiadis
Founded in 1997, Kiadis is building a fully integrated biopharmaceutical company committed to developing innovative therapies 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.

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