Kiadis Pharma presents pos­i­tive 1-year fol­low-up data of its piv­otal Phase II tri­al with ATIR101™

~ Significant reduc­tion in Transplant Related Mortality and improve­ment in Overall Survival observed in com­par­i­son to an obser­va­tion­al con­trol group ~

~ Zero patients devel­oped grade III-IV acute Graft-ver­sus-Host-Disease upon infu­sion of ATIR101™ ~

Amsterdam, The Netherlands, December 6, 2016, – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clin­i­cal stage bio­phar­ma­ceu­ti­cal com­pa­ny devel­op­ing inno­v­a­tive T-cell immunother­a­py treat­ments for blood can­cers and inher­it­ed blood dis­or­ders, today presents pos­i­tive one-year data with its lead prod­uct ATIR101™ from the sin­gle dose Phase II tri­al (NCT01794299/EudraCT 2012-004461-41) at the 58th Annual Meeting and Exposition of the American Society of Hematology (ASH) in San Diego, United States of America.
The data pre­sent­ed at ASH in ses­sion 711 by Dr. Denis-Claude Roy, Professor of Medicine at the University of Montreal, one of the prin­ci­pal inves­ti­ga­tors for the tri­al and pro­to­col chair, con­firms that ATIR101™ can be safe­ly infused and shows a sig­nif­i­cant reduc­tion in Transplant Related Mortality (TRM) (pri­ma­ry end­point) and a sig­nif­i­cant improve­ment in Overall Survival (OS) (sec­ondary end­point) in com­par­i­son to an obser­va­tion­al con­trol group of patients under­go­ing a T-cell deplet­ed hap­loiden­ti­cal donor trans­plan­ta­tion only. Combined with the lack of severe Graft-ver­sus-Host-Disease (GVHD) and lim­it­ed relapse, this trans­lates into favor­able GVHD-free, relapse-free sur­vival (GRFS) one-year post-trans­plan­ta­tion.
Manfred Rüdiger, PhD, Chief Executive Officer of Kiadis Pharma, com­ment­ed: “We are very excit­ed about the strong and com­pelling results from our Phase II tri­al. The data shows sub­stan­tial­ly improved Overall Survival rates and low Transplant Related Mortality. In addi­tion, with the infu­sion of ATIR101™, no inci­dents of life threat­en­ing grade III-IV GVHD were detect­ed, despite patients not receiv­ing any pro­phy­lac­tic immune-sup­pres­sants. Looking at the GRFS end­point, a com­pos­ite end­point used to present out­come data, our ATIR101™ approach com­pares very favor­ably with the post-trans­plant cyclophos­phamide pro­to­cols pio­neered in Baltimore. Having no grade III-IV GVHD and very low relapse rates makes us believe that ATIR101™ could become an attrac­tive alter­na­tive for patients who don’t have a match­ing donor. We will sub­mit a Marketing Authorization Application to the European Medicines Agency (EMA) for our data in the first quar­ter of 2017 and our next imme­di­ate step is the ini­ti­a­tion of our transat­lantic ran­dom­ized Phase III inter­na­tion­al con­trolled tri­al, com­par­ing our ATIR101™ approach direct­ly to the Baltimore approach.”

Dr. Denis-Claude Roy, Professor of Medicine at the University of Montreal, one of the prin­ci­pal inves­ti­ga­tors for the tri­al and pro­to­col chair, added: “With this lat­est data we can con­firm the safe­ty of ATIR101™, with­out any inci­dents of grade III-IV GVHD, sig­nif­i­cant reduc­tion in Transplant Related Mortality, low relapse rates and very good event free sur­vival, which we believe con­firms the effi­cien­cy of pho­tode­ple­tion-based elim­i­na­tion of allo-reac­tive T-cells. As a doc­tor, I am very excit­ed about this devel­op­ment and its poten­tial to change patient fates.”

Trial details
Twenty-three leukemia patients with a medi­an age of 41 years (range 21-64) were enrolled into and treat­ed on this tri­al from sites in Canada, Belgium, Germany and the United Kingdom. Patients were eli­gi­ble for an allo­gene­ic hematopoi­et­ic stem cell trans­plan­ta­tion (HSCT) but could not find a match­ing donor in time. Sixteen patients had acute myeloid leukemia (AML) and sev­en had acute lym­phoblas­tic leukemia (ALL). Patients were either in first or sec­ond com­plete remis­sion at the time of the HSCT. The major­i­ty of patients had a poor prog­no­sis based on their Disease Risk Index (DRI) (57% high/very high risk), while the remain­ing 43% had an inter­me­di­ate risk index. A mye­loab­la­tive con­di­tion­ing reg­i­men was used and (hap­loiden­ti­cal) donor grafts were deplet­ed of T-cells (CD34+ selec­tion) pri­or to trans­plan­ta­tion. Patients engraft­ed rapid­ly (medi­an twelve days) and ATIR101™ was sub­se­quent­ly infused at a fixed dose of 2×106 CD3+ cells/kg at a medi­an of 28 days post-trans­plant with­out use of any post-trans­plant GVHD pro­phy­lax­is.

The medi­an fol­low-up, on November 28, 2016, was 485 days (range 110-742) post-HSCT, at which point all patients were beyond one year post-HSCT.

No patients (0/23) devel­oped grade III-IV GVHD upon infu­sion of ATIR101™, con­firm­ing the effi­ca­cy of the elim­i­na­tion of allo-reac­tive T-cells from ATIR101™. Only three cas­es of grade II acute GVHD were report­ed after infu­sion of ATIR101™. In addi­tion, one case of chron­ic GVHD was report­ed after infu­sion of ATIR101™.

Despite the fact that the major­i­ty of patients were at high risk for relapse (DRI-high) only two patients devel­oped dis­ease relapse with­in the first twelve months after HSCT (at day 61 and day 90 post-HSCT respec­tive­ly). No mor­tal­i­ty was observed with­in the first 100 days post-HSCT. Nine patients died with­in the first year after trans­plan­ta­tion, sev­en due to TRM and two due to dis­ease relapse, result­ing in a one-year OS of 61%.

When com­pared to con­trol data from an obser­va­tion­al cohort study (con­sist­ing of a group of 35 patients match­ing the inclu­sion and exclu­sion cri­te­ria of the Company’s Phase II tri­al who under­went a sim­i­lar HSCT pro­ce­dure from hap­loiden­ti­cal fam­i­ly mem­bers but with­out the addi­tion of ATIR101™), OS was sig­nif­i­cant­ly high­er (p=0.003) in patients who were giv­en ATIR101™ after a T-cell deplet­ed hap­loiden­ti­cal trans­plan­ta­tion. The one-year OS for HSCT + ATIR101™ is 61% ver­sus 20% for HSCT only. TRM was sig­nif­i­cant­ly low­er (p=0.007), the one-year TRM for HSCT + ATIR101™ being 32% ver­sus 70% for HSCT only.

GRFS, defined as patients sur­viv­ing with­out get­ting severe acute GVHD (grade III-IV) or chron­ic GVHD (requir­ing sys­temic treat­ment) and with­out relaps­ing, for patients treat­ed with HSCT and an adju­vant infu­sion of ATIR101™ was 57% at one year. This com­pares favor­ably with patients in the con­tem­po­ra­ne­ous obser­va­tion­al con­trol group under­go­ing an HSCT only (with GRFS at 20%) and also with patients in that same con­trol group receiv­ing a Matched Unrelated Donor trans­plan­ta­tion (HLA 8/8 or 10/10 match), where the GRFS at one year is 41%. Compared to report­ed GRFS data for hap­loiden­ti­cal trans­plants done using the post-trans­plant cyclophos­phamide (PTCy) approach to con­trol GVHD, the GRFS of 57% at one year for the HSCT + ATIR101™ group is favor­able to the GRFS of 33% report­ed for the PTCy group (Solh et al, BBMT 2016).

Patients will con­tin­ue to be fol­lowed-up until two years post-HSCT in order to col­lect fur­ther long-term out­come data. Out of the 23 patients enrolled in the tri­al, five have already com­plet­ed the full two year fol­low-up alive and four patients are still alive on study. The final data from this tri­al will be avail­able in the sec­ond half of 2017.

Based on the pos­i­tive results from this Phase II tri­al, the Company is pro­ceed­ing with the devel­op­ment of ATIR101™ by ini­ti­at­ing a Phase III tri­al in which patients with acute leukemia will be ran­dom­ized to receive a hap­loiden­ti­cal HSCT accord­ing to either the PTCy approach or the Kiadis Pharma approach with a sin­gle dose of ATIR101™. This Phase III tri­al has been sub­mit­ted to reg­u­la­to­ry author­i­ties and is cur­rent­ly under review for approval.

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