Positive data on oral belinostat in phase I dose escalating study in Lymphoma presented at ASCO

Announcement No. 23-09 / Copenhagen, 30 May 2009	
TopoTarget A/S
Symbion
Fruebjergvej 3
DK 2100 Copenhagen
Denmark
Tel: +45 39 17 83 92
Fax: +45 39 17 94 92
CVR-nr: 25695771
www.topotarget.com


Copenhagen, Denmark - 30 May 2009 - TopoTarget A/S (OMX: TOPO) has announced
positive data from a phase I study of belinostat given as oral monotherapy day
1-14 every three weeks in patients with lymphoma presented at the ASCO
(American Society of Clinical Oncology) annual conference May 29 - Jun 2. Oral
belinostat can be delivered safely to lymphoma patients in doses that are
higher than the maximum tolerated dose for patients with solid tumors. Current
dose level is 1500 mg daily with 5 patients still ongoing. Despite extensive
pre-treatment, 7 of 10 evaluable patients have achieved stabilization of
disease for up to nine months. Early onset of tumor shrinkage has been seen in
patients with Hodgkin's disease and Mantle cell lymphoma. The acceptable safety
profile and early tumor shrinkage noted warrants continued evaluation of
belinostat in lymphoma, especially in combination with other active compounds. 

“These new positive data demonstrate that the oral form of belinostat can be
administered in higher doses than previously reported in solid tumors.
Belinostat has already at this stage and despite extensive prior treatments in
7 out of 10 evaluable patients achieved disease control for up to 9 months.
These findings and the flexibility in optimizing the dose to the cancer
patients is important for this new drug class”, says professor Peter Buhl
Jensen, CEO of TopoTarget. 


The study:
A phase I, open label, dose-escalation, multi-center study. Objectives are to
determine safety and dose limiting toxicity (DLTs) for oral belinostat in
patients with relapsed/refractory lymphoma and to assess preliminary efficacy. 

Belinostat treatment included day 1 to 14, once daily administration every 21
days with doses escalated in steps of 250 mg from 750 mg to current level of
1500 mg. 

Results: 
15 patients, median age 53 have been treated. Most common lymphoma types are
Mantle cell lymphoma (33%), Hodkin's disease (33%) and Cutaneous T-cell
lymphoma (13%). Most frequent related adverse events were anorexia, diarrhea
fatigue and vomiting as we know them from other studies of belinostat.
Hematological toxicity has been mild. The patients had in general been treated
with prior multiple lines of therapy median 4 (range 1-12). 
Stable disease (SD) seen in 7 of 10 extensive pre-treated evaluable patients,
including 3/3 patients with Mantle cell lymphoma, 3/4 patients with Hodgkin's
disease, and the only evaluable patient with Cutaneous T-cell lymphoma
(previously progressing on Vorinostat). Median treatment duration for patients
with SD is currently +77 days (range 62 to +282 days; 3 patients in ongoing
treatment). 

Even though no partial remissions (PRs) have been noted according to the
International Working Group criteria (Cheson 2007), tumor shrinkage of 43 to
49% has been observed in 1 patient with Hodgkin's disease and 2 of 3 evaluable
patients with Mantle cell lymphoma, after two cycles of therapy (first
assessment time point). 

Conclusions: 
Oral belinostat can be delivered safely with a day 1 to 14, q3 weekly, schedule
in patients with lymphoma. This dose is higher than the dose that has been
established for patients with solid tumors. No Dose limiting toxicities (DLTs)
have been seen at dose levels 750 to 1250 mg daily. At the current dose level
of 1500 mg daily 1 patient has experienced a DLT, thus the cohort has been
expanded. Most common adverse events have been anorexia, diarrhea, fatigue, and
vomiting. Hematological toxicity has been mild. Despite extensive pre-treatment
7 of 10 currently evaluable patients have achieved stabilization of disease for
up to nine months. Early onset tumor shrinkage has been seen in patients with
Hodgkin's disease and Mantle cell lymphoma. The acceptable safety profile and
early tumor shrinkage noted in Mantel cell lymphoma and Hodgkin's disease
warrants continued evaluation of belinostat in lymphoma, especially in
combination with other active compounds. 

TopoTarget A/S

For further information, please contact:

Peter Buhl Jensen	Telephone	+45 39 17 94 99
CEO		Mobile	+45 21 60 89 22