Profile: Allos Therapeutics Inc (ALTH.O)

Allos Therapeutics, Inc., incorporated on September 1, 1992, is a biopharmaceutical company that is focused on developing and commercializing small molecule drugs for the treatment of cancer. The Company’s lead product candidate, pralatrexate (PDX) an antifolate, is in Phase II trial in patients with relapsed or refractory peripheral T-cell lymphoma. The Company is also investigating PDX in patients with non-small cell lung cancer and a range of other lymphoma sub-types. The Company’s other product candidate is RH1, a targeted chemotherapeutic agent, which is in a Phase I trial in patients with advanced solid tumors or non-Hodgkin's Lymphoma. In February 2009, the Company announced the final results from PROPEL, its pivotal Phase II trial of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This trial was conducted under an agreement reached with the United States Food and Drug Administration (FDA) under its special protocol assessment (SPA) process, which provides an agreement that the study design, including trial size, clinical endpoints and/or data analyses are acceptable to the FDA.

Pralatrexate

PDX is a targeted antifolate designed to accumulate preferentially in cancer cells. pralatrexate selectively enters cells expressing RFC-1, a protein that is over expressed on cancer cells compared to normal cells. Once inside cancer cells, pralatrexate is polyglutamylated, which leads to high intracellular drug retention. Polyglutamylated pralatrexate essentially becomes trapped inside cancer cells, making it less susceptible to efflux-based drug resistance. Acting on the folate pathway, pralatrexate interferes with deoxyribonucleic acid (DNA) synthesis and triggers cancer cell death.

The Company’s trial called PROPEL is an international, multi-center, open-label, single-arm Phase II clinical trial of PDX in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The trial enrolled a total of 115 patients with relapsed or refractory PTCL, 109 of who were considered evaluable for response according to the trial protocol. The results of the trial demonstrated that 29 of 109 evaluable patients, or 27%, achieved a response as assessed by central independent oncology review. Of the 29 patients who achieved a response according to central independent oncology review, seven patients had a complete response (CR), two patients had a complete response unconfirmed (Cru), and 20 patients had a partial response (PR).

RH1

RH1 is a small molecule chemotherapeutic agent that is bioactivated by the enzyme DT-diaphorase, (DTD), also known as NAD(P)H quinone oxidoreductase (NQ01). In November 2007, the Company initiated patient enrollment in a Phase I, open-label, multi-center dose escalation study of RH1 in patients with advanced solid tumors (NHL).