NQO1

Even with a holiday week, July 4, there were a number of clinical trial reports. Here’s a look. Even with a holiday week, July 4, there were a number of clinical trial reports. Here’s a look. Biogen released new data from the NURTURE clinical trial, which adds data to the longest study of SMA in pre-symptomatic infants. SMA is a rare, genetic neuromuscular disease caused by a defective or missing SMN1 gene. Infants with SMA lose the motor neurons responsible for muscle functions such as breathing, swallowing, speaking and walking. The disease can lead to death. Biogen presented the new data at the Cure SMA Annual SMA Conference in Anaheim and at the 5 th Congress of the European Academy of Neurology (EAN) held in Oslo, Norway. The data reported the drug’s efficacy and safety for up to 45.1 months after treatment and demonstrated continuous improvement for the vast majority of patients achieving motor milestones in a normal timeframe. Pfizer ’s intravenous (IV) Revatio (sildenafil), when added to inhaled nitric oxide (iNO), failed to meet its primary efficacy endpoint in treating newborns with persistent pulmonary hypertension (PPHN). Revatio is approved to treat adults with pulmonary arterial hypertension (PAH). PPHN is another type of high blood pressure which can be life-threatening. Prior to birth, a baby’s blood circulates differently in the uterus. With PPHN, the child does not shift over from fetal to normal newborn circulation, and blood is forced away from the lungs because of the high blood pressure in the arteries leading to the lungs. This decreases oxygen supply to the body. The Phase III clinical trial had two consecutive parts. The first, Part A, was a randomized, placebo-controlled, double-blind interventional phase. It assessed the efficacy and safety of the therapy. The results reported today are based on Part A. Part B is the non-interventional phase with follow-up at 12 and 24 months after the end of the trial to evaluate developmental progress. Part B is ongoing. The trial did not result in a statistically significant decrease in treatment failure rate or time on iNO compared to treatment with iNO alone. Pfizer also reported initial Phase Ib clinical data on PF-06939926, a gene therapy for Duchenne muscular dystrophy (DMD). They presented the data at the 25 th Annual Parent Project Muscular Dystrophy (PPMD) Connect Conference held in Orlando, Florida. The primary endpoint of the Phase Ib trial was safety and tolerability of the therapy. Secondary endpoints measured expression of mini-dystrophin distribution within muscle fibers. DMD is a genetic disease marked by progressive muscle degeneration and weakness. It primarily affects boys. Boys with the disease often die in their 20s. The preliminary data showed the most common adverse events were nausea, vomiting, decreased appetite, tiredness and/or fever. Preliminary efficacy data included muscle biopsies of the biceps taken two months after dosing in a small subgroup of the trial. It showed detectable mini-dystrophin immunofluorescence signals with a mean of 38% positive fibers at one dose and 69% at a higher dose. Boston Biomedical reported that its CanStem111P trial investigating napabucasin plus weekly nab-paclitaxel with gemcitabine compared to weekly nab-paclitaxel with gemcitabine in metastatic pancreatic ductal adenocarcinoma is being halted. This was based on a recommendation by the independent Data and Safety Monitoring Board (DSMB) review that was scheduled for the halfway mark of the trial. Although there were no new safety concerns, the results apparently did not indicate there was sufficient efficacy to continue. Napabucasin is an oral drug bioactivated by NQO1, which creates reactive oxygen species (ROS) that affect multiple cancer pathways, including the STAT3 pathway. The drug is also being evaluated for metastatic colorectal cancer and in solid malignancies. Calithera Biosciences treated its first patient in a Phase I/II trial of its glutaminase inhibitor telaglenastat (CB-839) in combination with Pfizer’s CDK 4/6 inhibitor Ibrance (palbociclib). The trial will look at the combination to treat patients with KRAS-mutated colorectal cancer (CRC) and KRAS-mutated non-small cell lung cancer (NSCLC). Telaglenastat is designed to block glutamine consumption in cancer cells. Cancer cells consume a lot of energy, primarily glucose and glutamine, to support the increase in cell division. Mutations in KRAS allow for this increased metabolism. TG Therapeutics presented long-term follow-up data from the Phase II and Open-Label Extension (OLE) trial of ublituximab (TG-1101) in relapsing forms of multiple sclerosis (RMS). The drug appears to be well tolerated with a median duration of follow-up of 97.5 weeks. No patients discontinued the trial because of adverse events related to the drug. The data were presented at the 5 th Congress of the European Academy of Neurology (EAN) in Oslo, Norway. Genentech , a Roche company, announced that its Phase III MINISTONE-2 clinical trial hit its primary endpoint, showing that its Xofluza (baloxavir marboxil) was comparable to its own Tamiflu (oseltamivir). It was also well-tolerated in children with the flu. Genentech hasn’t released much actual data on the trial other than to say that it met its primary endpoint, showing that Xofluza was well-tolerated in the children and that it was comparable to Tamiflu at decreasing the symptoms and duration of the flu. Full results with be presented at an upcoming medical conference. The trial compared Xofluza to Tamiflu in children between the ages of one and 12 years with the flu. Tamiflu has been on the market for 20 years. Xofluza is approved broadly in Japan and for people older than 12 years in the U.S. The company is hoping to market Xofluza as an alternative to Tamiflu that is more convenient. Tamiflu has to be taken twice a day for five days, and is off-patent, making it vulnerable to generic copies. Unum Therapeutics announced that the FDA had placed a clinical hold on its Phase I non-Hodgkin lymphoma trial over safety concerns. This is the second clinical hold placed on the drug. The ATTCK-20-2 trial is evaluating ACTR087 in combination with Genentech’s Rituxan (rituximab) after lymphodepleting chemotherapy with fludarabine and cyclophosphamide in patients with relapsed/refractory CD20+ B-cell non-Hodgkin lymphoma. Apparently, one patient in the safety expansion cohort of the trial experienced serious adverse events including neurotoxicity, cytomegalovirus infection, and severe respiratory distress.

Pancreatic cancer is a particularly difficult cancer to treat, and although there have been advances in treatment, it is still an extremely deadly disease. Here’s a look at some recent news concerning pancreatic cancer. Pancreatic cancer is a particularly difficult cancer to treat, and although there have been advances in treatment, it is still an extremely deadly disease. Here’s a look at some recent news concerning pancreatic cancer. Boston Biomedical Abandons CanStem111P Study Boston Biomedical reported that its CanStem111P trial investigating napabucasin plus weekly nab-paclitaxel with gemcitabine compared to weekly nab-paclitaxel with gemcitabine in metastatic pancreatic ductal adenocarcinoma is being halted. This was based on a recommendation by the independent Data and Safety Monitoring Board (DSMB) review that was scheduled for the halfway mark of the trial. Although there were no new safety concerns, the results apparently did not indicate there was sufficient efficacy to continue. Napabucasin is an oral drug bioactivated by NQO1, which creates reactive oxygen species (ROS) that affect multiple cancer pathways, including the STAT3 pathway. The drug is also being evaluated for metastatic colorectal cancer and in solid malignancies. Cold Spring Harbor Laboratory IDs Way Cancer Cells Eat Themselves Researchers at Cold Spring Harbor Laboratory (CSHL) published research in the journal Cancer Discovery describing a way cancer cells attack their own mitochondria, which may be a new target for pancreatic cancer drugs. The scientists found that cancer cells appear to attack mitochondria because of reactive oxygen species (ROS) the mitochondria produce as a result of their energy production. The study focused on the KRAS protein which is active in the nutrient-depleted environment of pancreatic cancers. KRAS launches a signaling cascade that causes the cell to eat its own mitochondria and divert glucose and glutamine away from the rest of the mitochondria. A Technique for Starving Pancreatic Cancer Cells Because cancer cells of all types divide so fast, they consume a lot of fuel, usually in the form of glucose and glutamine. The process is called micropinocytosis. Researchers from Sanford Burnham Prebys have found a signaling pathway that regulate micropinocytosis in pancreatic tumors. “To find the metabolic Achilles’ heel of pancreatic cancer, we need a deeper understanding of how these tumors obtain nutrients,” stated Cosimo Commisso , senior author of the study and assistant professor in Sanford Burnham Prebys’ NCI-designated Cancer Center. “Our study reveals that, like people, pancreatic cancer metabolism is diverse. Some pancreatic tumors can ‘dial up’ or ‘dial down’ micropinocytosis depending on the availability of glutamine—an amino acid that plays a key role in the metabolism of rapidly growing cells. Other tumors have naturally high levels of ‘always on’ micropinocytosis. We also identified the molecular regulators of this process, which may ultimately lead to personalized treatments.” Pancreatic Cancer Action Network Appoints Andrew Lowy to Chair SMAB The Pancreatic Cancer Action Network (PanCAN) announced new leadership for its Scientific and Medical Advisory Board (SMAB). Andrew M. Lowy , Professor of Surgery and chief of the Division of Surgical Oncologica at the University of California San Diego School of Medicine will act as the new chair. Margaret A. Empero , director of the UCSF Pancreas Center and Professor of Medicine at the University of California, San Francisco , is the new chair-elect. CSHL Researchers Identify Possible Biomarker to test for Pancreatic Cancer Patients with pancreatic cancer overproduce CA19-9, a sugar molecule associated with the disease, but which was previously thought to be harmless. Now they found that it plans a significant role in causing pancreatic cancer. As it accumulates, it appears to attach to other molecules, changing the structure and function of those proteins. Danielle Engle , lead author of the study and a former postdoctoral fellow at Cold Spring Harbor Laboratory, who is now an assistant professor at the Salk Institute , stated, “This is one of those unique opportunities where prophylactic intervention of pancreatitis may lead to prevention of pancreatic cancer in at-risk patients. Pancreatitis is required for developing pancreatic cancer, and we might be able to prevent that transition in patients with pancreatitis by targeting CA19-9.” The clinical potential is great. If researchers can develop an antibody against CA19-9 that blocks pancreatic inflammation, it might help patients with chronic pancreatitis, and would potentially have benefits in decreasing the risk of pancreatic cancer.

WESTMINSTER, Colo., Nov. 9 /PRNewswire-FirstCall/ -- Allos Therapeutics, Inc. today reported financial results for the third quarter of 2005. For the three months ended September 30, 2005, the Company reported a net loss of $4.8 million, or $0.09 per share. This compares to a net loss of $4.6 million, or $0.15 per share, for the three months ended September 30, 2004. For the nine months ended September 30, 2005, the Company reported a net loss of $15.5 million, or $0.36 per share, compared to a net loss of $16.9 million, or $0.54 per share, for the same period last year. Cash, cash equivalents, and investments in marketable securities as of September 30, 2005 amounted to $59.4 million. Product Portfolio Update: EFAPROXYN(TM) (efaproxiral): * ENRICH, the Company's Phase 3 study of the radiation sensitizer EFAPROXYN in patients with brain metastases originating from breast cancer, continues to progress in line with Company expectations. The Company expects to complete patient enrollment in this trial during the second half of 2006 and report preliminary results approximately six months thereafter. * In September 2005, the Company announced the publication of results from its Phase 2 multi-center study of EFAPROXYN in patients with unresectable non-small cell lung cancer (NSCLC) receiving sequential chemoradiotherapy (S-CRT). Results from the study, which were reported in the September 1st edition of the Journal of Clinical Oncology, suggest that the addition of EFAPROXYN to S-CRT may improve survival over S-CRT alone without increasing radiation toxicity rates. * In October 2005, the Company withdrew its European Marketing Authorization Application (MAA) for its investigational radiation sensitizer REVAPROXYN(TM) (efaproxiral, EFAPROXYN(TM) in the United States) for use as an adjunct to whole brain radiation therapy for the treatment of patients with brain metastases originating from breast cancer. The Company believes that the ongoing ENRICH trial, if positive, together with other supporting data, should provide the additional data necessary to support the filing of a new MAA and the future approval of EFAPROXYN for the treatment of brain metastases originating from breast cancer in Europe. * Charles Scott, Ph.D., CBS Squared, is scheduled to present a quality adjusted survival analysis of the Phase 3 REACH study of EFAPROXYN in patients with brain metastases in a poster presentation titled "Improved survival, quality of life and quality-adjusted survival in breast cancer patients treated with efaproxiral + whole brain radiation therapy for brain metastases" at the San Antonio Breast Cancer Symposium on December 10, 2005. PDX (pralatrexate): * Enrollment in a Phase 1/2 study of PDX in patients with relapsed or refractory aggressive lymphoproliferative malignancies continues to progress in line with Company expectations. The Company expects to complete patient enrollment in the Phase 1 portion of this trial in the fourth quarter of 2005. * In January 2005, the Company initiated a Phase 1 dose escalation study of PDX with vitamin B12 and folic acid supplementation in patients with previously treated advanced NSCLC. The Company currently expects to complete patient enrollment in this trial in 2006. RH1: * Enrollment in a Phase 1 dose escalation study of RH1 in patients with advanced solid tumors continues to progress in line with Company expectations. The Company currently expects to complete enrollment in this trial in the fourth quarter of 2005. Sarah Danson, M.D., Department of Medical Oncology, Christie Hospital, is scheduled to report updated clinical and PK/PD data from an on-going Phase 1 study of RH1 in patients with advanced solid tumors in a poster presentation titled "Phase 1 Pharmacokinetic (PD) trial of the bioreductive drug RH1" at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on November 17, 2005. Corporate Highlights: * In October 2005, the only remaining securities class action lawsuit that had been brought against the Company and one of its officers in May 2004 was dismissed with prejudice. In an opinion dated October 20, 2005, the United States District Court for the District of Colorado concluded that the plaintiff's complaint failed to meet the legal pleading requirements applicable to its alleged claims. The plaintiff has until November 19, 2005 to determine whether it will appeal the decision to the U.S. Court of Appeals for the Tenth Circuit. * In July 2005, a shareholder of the Company commenced a stockholder's derivative action in the United States District Court for the District of Colorado against several current and former directors of the Company, naming the Company as a nominal defendant. The factual allegations in the derivative action were substantially the same as the factual allegations in the purported securities class action lawsuit filed in May 2004. On November 2, 2005, the court granted the parties joint motion for voluntary dismissal and dismissed the case without prejudice. Conference Call The Company will host a conference call to review its third quarter results on Wednesday, November 9, 2005, at 11 AM ET. The dial in number for U.S. residents to participate is 877-407-8031. International callers should dial 201-689-8031. Participants should reference the Allos Therapeutics conference call. Conference Call Replay An audio replay of the conference call will be available from 5:30 PM ET on Wednesday, November 9, 2005, until 11:59 PM ET on Wednesday, November 16, 2005. To access the replay, please dial 877-660-6853 (domestic) or 201-612-7415 (international); Replay pass codes (both required for playback): account # 286; conference ID # 175174. Webcast Allos Therapeutics will hold a live webcast of the conference call. The webcast will be available from the homepage and the investors/media section of the Company's web site at and will be archived for 30 days. About Allos Therapeutics, Inc. Allos Therapeutics, Inc. is a biopharmaceutical company focused on developing and commercializing innovative small molecule therapeutics for the treatment of cancer. The Company's lead product candidate, EFAPROXYN(TM) (efaproxiral), is a synthetic small molecule designed to sensitize hypoxic, or oxygen-deprived, tumor tissue during radiation therapy. EFAPROXYN is currently being evaluated as an adjunct to whole brain radiation therapy in a pivotal Phase 3 trial in women with brain metastases originating from breast cancer. The Company's other product candidates are: PDX (pralatrexate), a small molecule chemotherapeutic agent (DHFR inhibitor) currently under investigation as both a single agent and in combination therapy regimens in patients with non-small cell lung cancer and Non-Hodgkin's lymphoma; and RH1, a small molecule chemotherapeutic agent bioactivated by the enzyme DT-diaphorase currently under evaluation in patients with advanced solid tumors. For more information, please visit the Company's web site at: . Safe Harbor Statement This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements concerning our projected timelines for completion of enrollment and announcement of the results of our clinical trials, the potential safety and efficacy of EFAPROXYN for the treatment of patients with NSCLC receiving S-CRT or any other type of cancer, and other statements which are other than statements of historical facts. In some cases, you can identify forward- looking statements by terminology such as "may," "will," "should," "expects," "intends," "plans," anticipates," "believes," "estimates," "predicts," "projects," "potential," "continue," and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that we may experience difficulties or delays in our clinical trials, whether caused by adverse events, investigative site initiation rates, patient enrollment rates, regulatory issues or other factors; and that clinical trials may not demonstrate the safety and efficacy of our product candidates in their target indications. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2004, and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law. ALLOS THERAPEUTICS, INC. CONDENSED STATEMENTS OF OPERATIONS (in thousands ~ except share and per share information) (unaudited) Three-months ended Nine-months ended September 30, September 30, 2004 2005 2004 2005 Operating expenses: Research and development $2,203 $3,001 $7,638 $7,970 Clinical manufacturing 432 307 2,589 934 Marketing, general and administrative 2,035 2,005 6,989 6,813 Restructuring costs -- -- -- 380 Total operating expenses 4,670 5,313 17,216 16,097 Loss from operations (4,670) (5,313) (17,216) (16,097) Interest and other income, net 116 522 365 1,238 Net loss (4,554) (4,791) (16,851) (14,859) Dividend related to beneficial conversion feature of preferred stock -- -- -- (624) Net loss attributable to common stockholders $(4,554) $(4,791) $(16,851) $(15,483) Basic and diluted net loss per share $(0.15) $(0.09) $(0.54) $(0.36) Weighted average common shares: basic and diluted 31,153,489 55,015,757 31,134,311 43,045,637 ALLOS THERAPEUTICS, INC. CONDENSED BALANCE SHEETS (in thousands) (unaudited) December 31, September 30, 2004 2005 ASSETS Cash, cash equivalents and investments in marketable securities $23,849 $59,426 Other assets 1,344 1,512 Equipment and leasehold improvements, net 980 748 Total assets $26,173 $61,686 Liabilities and Stockholders' Equity Liabilities $2,310 $3,212 Stockholders' equity 23,863 58,474 Total liabilities and stockholders' equity $26,173 $61,686 Allos Therapeutics, Inc. CONTACT: Jennifer Neiman, Manager, Corporate Communications of AllosTherapeutics, Inc., +1-720-540-5227, jneiman@allos.com Web site: