Presented at ASCO data on the first set of patients from the

pivotal Phase III TK008 study: the survival benefit exeeds trial
tar!et in aute leu"aemia patients
MolMed S.p.A. (MLM.MI) provided at the 50th ASCO annual meeting new data from the ongoing
randomised pivotal hase III stud! on its "ell therap! produ"t #$ for high%ris& a"ute leu&aemia pa%
tients transplanted from partiall! mat"hed (haplo%identi"al) donors.
The intent-to-treat analysis of the first 24 patients treated with TK indicates a 74% 1-year disease
free survival (DFS as the pri!ary study endpoint" this result lar#ely e$ceeds the tar#et of %2% DSF
for the TK ar! vs &'% for the control ar!(
)ota*ly+ ,-% of patients treated with TK were alive at one year (the .ey secondary study endpoint
and the correspondin# fi#ures for patients who achieved i!!une reconstitution rose to ,%% for
disease free survival and 1''% for overall survival(
The direct i!pact of TK cells on transplant outco!e was confir!ed *y a very low incidence of
relapse (1-% - with no relapse in patients receivin# hi#her TK cell doses and non-relapse !ortality
(1'% - with no deaths o*served in patients achievin# i!!une reconstitution(
/laudio 0ordi#non+ /hair!an and /12 of 3ol3ed+ co!!ented" '(e are parti"ularl! proud of the
results presented toda! at the ASCO meeting on the pivotal hase III trial of the #$ "ell therap! for
a"ute high ris& leu&emia patients transplanted from partiall! mat"hed famil! donors. (hen we
started this stud!) our goal was to provide all patients affe"ted *! the most aggressive forms of
leu&emia with the opportunit! to undergo *one marrow transplantation) *! far their *est "han"e
for a permanent "ure. +or this purpose we developed the #$ therap! that allows patients la"&ing a
full! mat"hed donor to a""ess a safer transplantation from partiall! mat"hed famil! donors) an
approa"h availa*le to nearl! all patients. #$ is *ased on the geneti" engineering of the donor
immune s!stem that "an offer a graft without post%transplant immune%suppression and provide for
a rapid and "omplete re"onstitution of the immune s!stem. #his therapeuti" strateg! is
"hara"teri,ed *! low infe"tion ris&) low leu&emia relapse rate and) "onse-uentl!) *! a higher
pro*a*ilit! of "ure. #oda! we report data on the first patients enrolled in this stud! with an
out"ome that e."eed the target of the trial design. #hese results strongl! support our "ommitment
to "omplete this large pivotal hase III stud!. Moreover) the relevan"e of the data presented at
ASCO is an important validation of our strategi" de"ision to pursue Conditional Mar&eting
Authori,ation for #$ in /urope0.
3ol3ed has *een investin# on the TK cell therapy that represents today the lar#est clinical
e$perience of i!!uno-#ene therapy of tu!ours worldwide( This e$tensive pro#ra! was carried
out throu#h the i!ple!entation of a centralised !anufacturin# in a sin#le facility for #lo*al
distri*ution( This e$perience+ coupled with the new facilities *uilt *y 3ol3ed+ represent today an
ideal platfor! for all new technolo#ies of tu!our i!!une-#ene therapy *ased on the different
strate#ies of #enetic en#ineerin# of the i!!une syste!(
The /o!pany would li.e to than. all patients and their fa!ilies who placed confidence in this new
technolo#y and all the investi#ators fro! all transplantation centres who participate the 4hase 555
trial and who contri*uted to the previous studies(
TK'', is coordinated *y Dr( Fa*io /iceri+ 3(D( fro! the San 6affaele Scientific 5nstitute+ principal
investi#ator of the trial who illustrated the results at 7S/2 and co!!ented" 'Initial results of the
hase III stud! indi"ate that in haploidenti"al transplant re"ipients #$%"ell infusions a*ate non%
relapse mortalit! and leu&emia relapse *! providing a fast immune re"over! in a dose%dependent
manner. 1S2%#$ sui"ide gene ma"hiner! effe"tivel! and timel! "ontrolled the graft%vs%host disease
(3v14) in 5006 of affe"ted patients with no re-uirement for long%term immune%suppressive
treatment. 7esults o*tained so far appear largel! superior to the out"omes reported *! large /8M#
surve!s for the two treatment options of #$009 "ontrol arm: #%"ell depleted and #%"ell replete
followed *! high%dose "!"lophosphamide. #hese results are of parti"ular relevan"e in light of the
more a""essi*le standard option represented *! haploidenti"al transplants.0
About TK
TK is a cell therapy product+ *ased on the use of #enetically en#ineered donor T cells carryin# a
8suicide #ene9( These cells are ad!inistered to patients durin# the hae!atopoietic ste! cell
transplantation for the treat!ent of hi#h ris. leu.ae!ia( TK therapy allows to eli!inate the post-
transplant i!!unosuppression treat!ent thus acceleratin# the i!!une reconstitution and
controllin# the i!!unolo#ical conse:uences arisin# fro! the #enetic differences with the donor+
.nown as ;raft versus <ost Disease (;v<D(
5n virtue of this approach+ <S/T fro! partially co!pati*le donors is a safer and !ore effective
option+ thus potentially increasin# the nu!*er of candidates for transplantation(
0ased on the efficacy and safety data and on the 2rphan Dru# desi#nation+ the /o!pany filed a
re:uest for /onditional 3ar.etin# 7uthorisation of TK with the 1uropean 3edicine 7uthority in
3arch 2'14(
TK008 study
TK'', is a pivotal rando!ised 4hase 555 trial (TK'', in adult patients affected *y hi#h-ris.
leu.ae!ia under#oin# transplant of hae!atopoietic ste! cells collected fro! partially co!pati*le
(haploidentical fa!ily donors( The trial co!pares the outco!e of haplo-transplants with or
without TK add-*ac.s+ with a &"1 rando!isation ratio in favour of the TK ar!(
The pri!ary study end-point is disease-free survival (DFS - which includes *oth transplant-related
!ortality and disease relapse - evaluated on 17' patients( The study is powered to detect an
increase in 1-year DFS fro! &'% in the control ar! to %2% in the e$peri!ental ar!( Secondary
end-points include overall survival+ reduction of transplant-related !ortality+ safety and patients=
:uality of life(
>ith the ai! to provide additional clinical *enefit to patients and to si#nificantly increase the
potential participation of centres in the trial+ the /o!pany i!ple!ented in 2'12 two i!portant
chan#es in the protocol desi#n of 4hase 555 trial TK'',( The first consists in *roadenin# the
enrol!ent criteria to include patients in leu.ae!ic relapse+ in addition to those in disease
re!ission? the second chan#e provides for the introduction of a further treat!ent option in the
control ar!+ *ased on the use of an un!anipulated transplant followed *y cyclophospha!ide
ad!inistration durin# the post-transplantation period(
This press release is written in co!pliance with pu*lic disclosure o*li#ations esta*lished *y
/2)S20 (5talian securities @ e$chan#e co!!ission resolution no( 11A71 of 14 3ay 1AAA+ as
su*se:uently a!ended(
About #ol#ed
3ol3ed S(p(7( is a *iotechnolo#y co!pany focused on research+ develop!ent and clinical valida-
tion of novel anticancer therapies( 3ol3ed=s pipeline includes two antitu!our therapeutics in clin-
ical develop!ent" TK+ a cell-*ased therapy ena*lin# *one !arrow transplants fro! partially co!-
pati*le donors+ in a*sence of post-transplant i!!une-suppression+ in 4hase 555 in hi#h-ris. acute
leu.ae!ia? );6-hT)F+ a novel vascular tar#etin# a#ent+ in 4hase 555 in !ali#nant pleural !esothe-
lio!a and in 4hase 55 in si$ !ore indications" colorectal+ lun# (s!all-cell and non-s!all-cell+ liver
and ovarian cancer+ and soft tissue sarco!as( 3ol3ed also offers top-level e$pertise in cell and
#ene therapy to third parties to develop+ conduct and validate proBects fro! preclinical to 4hase 555
trials+ includin# scale-up and c;34 production of clinical-#rade viral vectors+ and !anufacturin# of
patient-specific #enetically en#ineered cells( 3ol3ed is head:uartered at the San 6affaele 0io-
!edical Science 4ar. in 3ilan+ 5taly( The /o!pany=s shares are listed on the !ain !ar.et (3T7 of
the 3ilan Stoc. 1$chan#e( (Tic.er 6euters" 3C3D(35
$O%T&: #ol#ed'om