Telik Announces Phase 1 Results of a Multicenter Study of Telintra® (Ezatiostat Hydrochloride, TLK199) in Combination with Revlimid® (Lenalidomide) in Patients with Myelodysplastic Syndrome

PALO ALTO, Calif., Dec. 13, 2011 /PRNewswire/ -- Telik, Inc. (Nasdaq: TELK) today announced positive results from a Phase 1 multicenter dose-ranging trial of the combination of Telintra and Revlimid in patients with International Prognostic System Score (IPSS) Low to Intermediate-1 Risk non-deletion (5q) myelodysplastic syndrome (MDS).  

The majority of MDS patients are Low to Intermediate-1 Risk non-deletion (5q) and represent an important unmet medical need.  Although Revlimid currently is not approved for the treatment of non-deletion (5q) MDS it is used in this setting because of limited alternatives.  The rationale for the combination of Telintra and Revlimid is based on Telintra's novel mechanism of action, lack of suppression of white blood cell levels and the efficacy seen in single-agent Phase 1 and Phase 2 studies in the Low to Intermediate-1 Risk non-deletion (5q) MDS patient population.

The primary objective of the study was to establish the safety of the combination and the optimal dosing for Telintra in combination with the standard dose of Revlimid.  The secondary objectives were to assess the efficacy as measured by rates of hematologic improvement in red blood cell, white blood cell and platelet levels, and decreases in blood transfusions, according to International Working Group criteria (IWG 2006).  

Nineteen patients were treated at 9 investigational centers.  Patients received Telintra at a starting dose of 2000 mg in combination with standard dose Revlimid (10 mg) on days 1-21 of a 28-day cycle.  In stage 1, 3-6 patients in a standard 3+3 design were treated before escalation to the 2500 mg Telintra and 10 mg Revlimid dose levels.  The optimal dose of the combination was 2000 mg Telintra and 10 mg of Revlimid.  This cohort was expanded by an additional 10 patients in stage 2.

The median age was 75 years, with 5 patients having IPSS Low Risk classification and 14 patients having Intermediate-1 Risk.  Thirteen of 19 patients (68%) were red blood cell transfusion-dependent and required a median of 6 units of blood (range 4-10) during an 8 week period.  Two patients were platelet transfusion-dependent and 4 additional patients (21%) had clinically-significant low platelet levels.  

At the time of preliminary analysis, 4 of 19 patients (21%) remain on treatment with continuing clinical benefit.  Of 79 cycles of combination treatment administered, only 7 cycles (9%) required dose reductions and 10 cycles (13%) dose delays.  

Thirteen patients received the dose selected for further study of 2000/10 mg, and 10 were evaluable for efficacy.  All patients were evaluable for safety.  

At the 2000/10 mg combination dose, 4 of 10 patients (40%) met the hematologic improvement in red blood cell levels (HI-E) response criterion.  Seven patients were transfusion dependent, and 3 (43%) achieved transfusion independence, including one who did not respond to prior Revlimid monotherapy.  All red blood cell transfusion-dependent patients who responded to the combination therapy were in the 2000/10 mg dose group.  The median duration of red blood cell transfusion independence and HI-E response has not been reached.  

All multilineage responses were also observed in the 2000/10 mg dose group.   Three of 5 patients (60%) with low platelet levels had a hematologic improvement in platelet levels (HI-P) response.  One of the 3 patients with platelet transfusion dependence achieved platelet transfusion independence.  

One of 3 patients with low white cell levels achieved a hematologic improvement in white blood cell levels (HI-N) response.  

Bilineage responses included:

• HI-E and HI-P responses in 3 of 5 patients
• HI-E and HI-N responses in 1 of 3 patients
• HI-N and HI-P responses in 1 of 3 patients

One of 3 patients with trilineage low blood cell levels had a complete response of all 3 blood cell lineages.  

One red blood cell and platelet transfusion-dependent patient who did not respond to prior anti-thymocyte globulin treatment achieved complete red blood cell and platelet transfusion independence.  

The combination of Telintra and Revlimid was generally well tolerated with no unexpected new toxicities and the observed toxicities were those expected from either agent alone.  Most common treatment-related non-hematologic adverse events (AEs) in the combined dose levels were gastrointestinal, including anorexia, nausea, vomiting and diarrhea.  Most common hematologic-related AEs were thrombocytopenia, neutropenia and anemia.    

Telintra is the first GST P1-1 enzyme inhibitor shown to cause clinically-significant reduction in red blood cell and platelet transfusions, including transfusion independence, as well as trilineage hematologic improvement including HI-E, HI-N and HI-P.  Since Telintra is non-myelosuppressive, it is a good candidate for combination therapy with Revlimid.  In this study, the combination was well tolerated and provided a unique profile of activity with platelet transfusion independence and trilineage and bilineage responses, which was also seen with single-agent Telintra.  Interestingly, one patient who had previously failed to respond to single-agent Revlimid subsequently responded to the combination of Telintra plus Revlimid.  The tolerability and activity profile of Telintra in combination with Revlimid may offer an important treatment option for patients with Low to Intermediate-1 Risk, non-del (5q) MDS.  These findings support the further development of Telintra alone and in combination with Revlimid for MDS and other hematologic malignancies.  

Background on MDS and Telintra

The myelodysplastic syndrome is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis (blood cell production) involving one or more cell lineages (red blood cells, white blood cells or platelets) and a variable risk of transformation to acute myeloid leukemia.  It is estimated that MDS affects approximately 300,000 people worldwide. According to a study published in the Journal of Clinical Oncology by Goldberg et al. (June 2010), 45,000 new cases of MDS are diagnosed each year in the United States, with survival rates ranging from six months to six years. MDS patients often require multiple blood transfusions to manage their disease.

Telintra has a novel mechanism of action that inhibits an enzyme called glutathione S-transferase P1-1, which leads to activation of Jun kinase, a key regulator of cellular growth and differentiation of blood precursor cells; and induces cancer cell death, or apoptosis, in human leukemia cell lines. Telintra is currently being evaluated in a Phase 2 clinical study in Revlimid® refractory and resistant deletion (5q) MDS patients; and in a Phase 2b clinical study in non-deletion (5q) MDS patients.  Additional information about Telintra is available at www.telik.com .

About Telik

Telik, Inc. of Palo Alto, CA, is a clinical stage drug development company focused on discovering and developing small molecule drugs to treat cancer.  The company's most advanced drug candidate is Telintra®, a modified glutathione analog intended for the treatment of hematologic malignancies including myelodysplastic syndrome; followed by Telcyta®, a cancer activated prodrug for the treatment of a variety of cancers. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP®, which enables the rapid and efficient discovery of small molecule drug candidates.

This press release contains "forward-looking" statements regarding the future development of Telintra, the safety, tolerability and effectiveness of Telintra in treating MDS, the effect of Telintra on white blood cell levels, whether Telintra treatment alone or in combination with Revlimid results in hematologic improvement or transfusion reduction or independence in patients with MDS, whether Telintra treatment offers an alternative to blood transfusions, and data relating to the clinical trial described above. These forward-looking statements are based upon Telik's current expectations and there are important factors that could cause actual results to differ materially from those indicated by these forward-looking statements. Detailed information regarding factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in Telik's periodic filings with the Securities and Exchange Commission, including the factors described in the section entitled "Risk Factors" in its quarterly report on Form 10-Q for the period ending September 30, 2011. Telik does not undertake any obligation to update forward looking statements contained in this press release.

Telik, the Telik logo, TELINTRA, TELCYTA and TRAP are trademarks or registered trademarks of Telik, Inc.

SOURCE Telik, Inc.