Full Press Release Details
MANAGEMENT DISCUSSION & ANALYSIS
FORWARD-LOOKING STATEMENTS
REOLYSIN DEVELOPMENT UPDATE FOR 2010
Clinical Trial Program
Clinical Trial - Program Expansion
Clinical Trial - 2010 Results
Pre-Clinical and Collaborative Program
Manufacturing and Process Development
Intellectual Property
Bought Deal Financing
REOLYSIN DEVELOPMENT FOR 2011
CRITICAL ACCOUNTING POLICIES AND ESTIMATES
SELECTED ANNUAL INFORMATION
RESULTS OF OPERATIONS
SUMMARY OF QUARTERLY RESULTS
LIQUIDITY AND CAPITAL RESOURCES
Bought Deal Financing
OFF-BALANCE SHEET ARRANGEMENTS
TRANSACTIONS WITH RELATED PARTIES
FINANCIAL INSTRUMENTS AND OTHER INSTRUMENTS
RISK FACTORS AFFECTING FUTURE PERFORMANCE
OTHER MD&A REQUIREMENTS
Disclosure Controls and Procedures
MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
The following information should be read in conjunction with our 2010 audited consolidated financial statements and notes thereto, which were prepared in accordance with Canadian generally accepted accounting principles ("GAAP").
FORWARD-LOOKING STATEMENTS
The following discussion contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended and under applicable Canadian provincial securities legislation. Forward-looking statements, including our belief as to the potential of REOLYSIN , a therapeutic reovirus, as a cancer therapeutic and our expectations as to the success of our research and development and manufacturing programs in 2011 and beyond, future financial position, business strategy and plans for future operations, and statements that are not historical facts, involve known and unknown risks and uncertainties, which could cause our actual results to differ materially from those in the forward-looking statements.
Such risks and uncertainties include, among others, the need for and availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN as a cancer treatment, the success and timely completion of clinical studies and trials, our ability to successfully commercialize REOLYSIN , uncertainties related to the research, development and manufacturing of REOLYSIN , uncertainties related to competition, changes in technology, the regulatory process and general changes to the economic environment.
With respect to the forward-looking statements made within this MD&A, we have made numerous assumptions regarding among other things: our ability to obtain financing to fund our development program, our ability to receive regulatory approval to commence enrollment in our clinical trial program, the final results of our co-therapy clinical trials, our ability to maintain our supply of REOLYSIN and future expense levels being within our current expectations.
Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Forward-looking statements are based on assumptions, projections, estimates and expectations of management at the time such forward-looking statements are made, and such assumptions, projections, estimates and/or expectations could change or prove to be incorrect or inaccurate. Investors are cautioned against placing undue reliance on forward-looking statements. We do not undertake to update these forward-looking statements except as required by applicable law.
REOLYSIN DEVELOPMENT UPDATE FOR 2010
Oncolytics Biotech Inc. is a Development Stage Company
Since our inception in April of 1998, Oncolytics Biotech Inc. has been a development stage company and we have focused our research and development efforts on the development of REOLYSIN , our potential cancer therapeutic. We have not been profitable since our inception and expect to continue to incur substantial losses as we continue research and development efforts. We do not expect to generate significant revenues until, if and when, our cancer product becomes commercially viable.
Our goal each year is to advance REOLYSIN through the various steps and stages of development required for potential pharmaceutical products. In order to achieve this goal, we believe that we have to actively manage the development of our clinical trial program, our pre-clinical and collaborative programs, our manufacturing process and REOLYSIN supply, and our intellectual property.
Clinical Trial Program
We began 2010 with eight clinical trials, either enrolling patients or approved to commence enrollment. We sponsor four of these eight clinical trials which include our randomized Phase III head and neck clinical trial associated with our Special Protocol Assessment agreement with the U.S. Food and Drug Administration ("FDA"). Of the four other clinical trials one was sponsored by the U.S. National Cancer Institute ("NCI"), two were sponsored by the Cancer Therapy & Research Center at The University of Texas Health Center in San Antonio ("CTRC") and one was sponsored by the University of Leeds ("Leeds").
In 2010, enrollment in our randomized Phase III head and neck trial commenced and we expanded into other jurisdictions including the U.K., Belgium, and Canada.
We also expanded our clinical program in 2010, to include a Phase II squamous cell carcinoma of the lungs cancer study (sponsored by the CTRC), a Phase I colorectal cancer study (sponsored by Oncolytics), a Phase II pancreatic cancer clinical study (sponsored by the CTRC), a randomized Phase II ovarian cancer study (sponsored by the Gynecologic Oncology Group ("GOG")), and a Phase I study in pediatric patients with relapsed or refractory solid tumours (sponsored by the NCI).
During the year, we presented positive updated results from our U.K. Phase I/II clinical trial focused on the head and neck at the ASCO annual meeting and published final results of our U.K. Phase Ia/Ib radiotherapy clinical trial and our U.K. Phase I docetaxel combination clinical trial. We also completed patient enrollment in our U.S. Phase I/II recurrent malignant glioma clinical trial and our Phase II sarcoma clinical trial.
We exited 2010 with eleven clinical trials which includes two randomized studies (our randomized Phase III head and neck trial and our randomized Phase II ovarian cancer trial). Five of the eleven trials are funded by us and the remainder are sponsored by the NCI, CTRC, and Leeds. Our clinical trial program currently encompasses various cancer indications including head and neck, non-small cell lung, ovarian, pancreatic, colorectal, melanoma, and squamous cell carcinoma of the lung among others.
Clinical Trial - Randomized Phase III Head and Neck Pivotal Trial
In 2010, we commenced enrollment in our randomized Phase III head and neck pivotal trial and throughout the year we expanded enrollment into other jurisdictions and sought out and initiated clinical sites within each jurisdiction. We obtained approval to conduct our randomized Phase III trial in the U.S., U.K. and Belgium. This is the same trial that we previously reached an agreement on with the FDA under the SPA process.
This trial is a randomized, two-arm, double-blind, multicentre, two-stage, adaptive Phase III trial that will assess the intravenous administration of REOLYSIN with the chemotherapy combination of paclitaxel and carboplatin versus the chemotherapy alone in patients with metastatic or recurrent squamous cell carcinoma of the head and neck, or squamous cell cancer of the nasopharynx, who have progressed on or after prior platinum-based chemotherapy. All patients will receive treatment every three weeks (21 day cycles) with paclitaxel and carboplatin and will also receive, on a blinded basis, either intravenous placebo or intravenous REOLYSIN. All dosing takes place in the first five days of each cycle with all patients receiving standard intravenous doses of paclitaxel and carboplatin on day one only, and on days one through five, either intravenous placebo or intravenous REOLYSIN at a dose of 3x1010 TCID50. Patients may continue to receive the trial combination therapy for up to eight, 21-day cycles and, thereafter, blinded placebo or blinded REOLYSIN until the patient has progressive disease or meets other criteria for removal from the trial.
The primary endpoint for the trial is overall survival (OS); secondary endpoints include progression free survival (PFS), objective response rate (complete response (CR) + partial response (PR)) and duration of response, and safety and tolerability of REOLYSIN when administered in combination with paclitaxel and carboplatin. The first stage of the trial is designed to enroll 80 patients. The second stage is adaptive, and is designed to enroll between 100 and 400 patients with the most probable statistical enrolment being 195 patients in this stage. This adaptive trial design allows frequent data evaluation to determine if the probability of reaching a statistically significant endpoint has been achieved.
The decision to pursue a Phase III trial in head and neck cancers was predicated on positive results seen in our Phase I and Phase II combination REOLYSIN and paclitaxel/carboplatin clinical trials, as well as significant preclinical work demonstrating synergy in combination with taxane or platinum-based drugs. Updated results from the U.K. Phase I/II trial reported in 2010 demonstrated an overall response rate (PR and CR) of 42% and a total clinical benefit rate (PR + CR + stable disease) of 74%.
Clinical Trial - Program Expansion
U.S. Randomized Phase II Combination REOLYSIN Paclitaxel Clinical Trial for Ovarian Cancer
In 2010, the GOG received approval to commence a randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN in patients with persistent or recurrent, ovarian, fallopian tube or primary peritoneal cancer (GOG186H) and commenced enrollment. The study will be sponsored by the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the NCI, under our Clinical Trials Agreement. The Study Chair will be Dr. David E. Cohn of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
This study is a randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer. Patients will be randomized to receive either paclitaxel alone or paclitaxel plus REOLYSIN. Patients in both arms will receive treatment with paclitaxel, with the second arm also receiving intravenous REOLYSIN. Patients will receive standard doses of paclitaxel on days one, eight, and 15 every 28 days. In the second arm, patients will also receive, on days one through five of each 28-day cycle, intravenous REOLYSIN at a dose of 3x1010 TCID50.
The primary objectives of this trial are to estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel with REOLYSIN to weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer and to determine the frequency and severity of adverse events associated with treatment with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN as assessed by Common Terminology Criteria for Adverse Events (CTCAE). The secondary objectives are to estimate the progression-free survival and overall survival of patients treated with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN ; to estimate (and compare) the proportion of patients who respond to the regimen on each arm of the study (according to RECIST 1.1 with measurable patients and by CA-125 for those patients with detectable disease only); and to characterize and compare progression-free survival and overall survival in patients with measurable disease (RECIST 1.1 criteria) and patients with detectable (nonmeasurable) disease. The study is expected to enroll up to 150 patients.
U.S. Phase II Pancreatic Cancer Clinical Trial
In 2010, the CTRC started patient enrolment in a U.S. Phase II clinical trial using intravenous administration of REOLYSIN in combination with gemcitabine (Gemzar ) in patients with advanced pancreatic cancer. The Principal Investigator is Dr. Monica Mita of the CTRC.
This trial is a single arm, open-label, Phase II study of REOLYSIN given intravenously with gemcitabine every three weeks. Up to 33 patients are expected to be treated in this trial. Eligible patients include those with advanced or metastatic pancreatic cancer with measurable disease who have not received any prior chemotherapy or biotherapy.
The primary objective of the Phase II trial is to determine the clinical benefit rate (complete response + partial response + stable disease) of intravenous multiple doses of REOLYSIN in combination with gemcitabine in patients with advanced or metastatic pancreatic cancer. The secondary objectives are to determine the progression-free survival, and to determine the safety and tolerability of REOLYSIN when administered in combination with gemcitabine.
This trial is the third of five clinical trials with the CTRC under our broad preclinical and clinical collaboration contract. Our collaboration with CTRC will involve up to five, open-label, Phase 2 studies exploring the use of REOLYSIN in combination with chemotherapy for various cancer indications.
U.S. Phase 1 Colorectal Cancer Clinical Trial
In 2010, we initiated a U.S. Phase 1 study of REOLYSIN in combination with FOLFIRI (Folinic Acid (leucovorin) + Fluorouracil (5-FU) + Irinotecan) in patients with oxaliplatin refractory/intolerant Kras mutant colorectal cancer. The principal investigator is Dr. Sanjay Goel of the Montefiore Medical Center at The Albert Einstein College of Medicine in New York.
The trial is a Phase I dose escalation study with three dose levels and cohorts of three to six patients to determine a maximum tolerated dose and dose-limiting toxicities with the combination of REOLYSIN and FOLFIRI. FOLFIRI will be administered on the first day of a two week (14 day) cycle, while REOLYSIN will be administered on days one through five of a four week (28 day) cycle. Eligible patients include those with histologically confirmed cancer of the colon or rectum with Kras mutation and measurable disease. They must have progressed on or within 190 days after last dose of oxaliplatin regimen as front-line therapy in the metastatic setting or be intolerant to oxaliplatin.
The clinical rationale for conducting this study was based on positive efficacy results seen in a range of our prior preclinical and clinical work with REOLYSIN. This includes a National Cancer Institute screen of seven colorectal cancer cell lines (four with ras mutations), all of which were susceptible to REOLYSIN; preclinical research into the efficacy of REOLYSIN in combination with various chemotherapeutic agents in colorectal cancer cell lines; observation of CEA responses and stable disease in colorectal patients in a Phase I study of REOLYSIN as a monotherapy; and evidence of viral replication of reovirus in liver metastases in patients with metastatic colorectal cancer in a translational study with REOLYSIN as a monotherapy that is currently ongoing.
U.S. Phase I Study in Pediatric Patients with Relapsed or Refractory Solid Tumors
In 2010, we expanded our clinical program to include pediatric patients. We announced that the Children's Oncology Group (COG) intends to conduct a Phase I trial of REOLYSIN in combination with cyclophosphamide in pediatric patients with relapsed or refractory solid tumors. The study will be conducted under our Clinical Trials Agreement with the NCI and in collaboration with the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute, which is part of the National Institutes of Health. The study chair will be Dr. E. Anders Kolb of the Nemours/Alfred I. duPont Hospital for Children.
The study is an open label, multicentre, dose escalation Phase I study of REOLYSIN in patients aged three to 21 years with relapsed or refractory solid tumors. Patients will receive intravenous REOLYSIN on days one through five of each 28-day treatment cycle. Some patients will also receive oral cyclophosphamide on days one through 21. Treatments repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
The primary objectives of the trial include estimating maximum tolerated dose, and defining and describing the toxicities of REOLYSIN and REOLYSIN plus oral cyclophosphamide in this patient population. Secondary objectives include defining antitumor activity of REOLYSIN within the confines of a Phase I study, evaluating the development of neutralizing antibodies to REOLYSIN following intravenous administration of REOLYSIN alone and in combination with cyclophosphamide, and assessing the biologic activity of REOLYSIN. After completion of study treatment, patients are to be followed up periodically for up to one year.
Clinical Trial - 2010 Results
U.K. Phase I/II REOLYSIN in Combination with Paclitaxel/Carboplatin
In 2010, a poster was presented covering updated results of our Phase I/II U.K. clinical trial of REOLYSIN combined with paclitaxel/carboplatin for patients with advanced cancers at the ASCO 2010 Annual Meeting in Chicago, IL.
The poster entitled "Phase I/II Study of Oncolytic Reovirus Plus Carboplatin/Paclitaxel in Patients with Advanced Solid Cancers with Emphasis on Squamous Cell Carcinoma of the Head and Neck," (SCCHN) updated our previously disclosed interim data to include new overall survival data.
The researchers reported that 31 patients were enrolled (24 males; median age 59 years) with head and neck cancer (n=24), melanoma (n=4), peritoneal/endometrial cancer (n=2), or sarcoma (n=1). In the dose-escalation phase of the study, there were no dose-limiting toxicities. Grade 3/4 toxicities included anaemia, leucopenia, neutropenia, lymphopenia, thrombocytopenia, infection and hypotension. In the Phase II study, PR were noted in two of five patients with head and neck cancer. The Phase II study treated head and neck cancer patients at the maximum dose level (3 x 1010 TCID50) in order to further assess tumour response. In total, 19 patients with head and neck cancer received at least two cycles and were evaluable for response. Most were SCCHN patients refractory to previous platinum-based chemotherapy for recurrent/metastatic disease. Partial responses were seen in eight patients (42%) and stable disease (SD) in six (32%). One additional PR and one SD were observed among four patients with malignant melanoma.
The mean overall survival (OS) in 24 treated head and neck cancer patients is more than eight months, with four patients still alive at the time of the presentation. The mean OS of the patients experiencing PR and PR plus SD is statistically significantly greater than the mean survival of those patients experiencing progressive disease (PD) (hazard ratio 0.2, p=0.0249 and hazard ratio 0.27, p=0.04, respectively, with a 95% confidence interval).
The researchers concluded that intravenous administration of reovirus in combination with carboplatin/paclitaxel is a safe and well-tolerated combination with promising anticancer activity in SCCHN. Further evaluation of this combination in a randomized Phase III trial in SCCHN is underway.
U.K. Phase Ia/Ib REOLYSIN in Combination with Radiotherapy Clinical Trial
In 2010, a paper entitled "Two-Stage Phase I Dose-Escalation Study of Intratumoural Reovirus Type 3 Dearing and Palliative Radiotherapy in Patients with Advanced Cancers," was published in the online version of the journal Clinical Cancer Research.
The paper covers final results from our Phase Ia/Ib U.K. clinical trial investigating the intratumoural delivery of REOLYSIN in combination with radiation to treat patients with advanced cancers. A total of 23 patients received a range of two to six intratumoural doses of REOLYSIN at escalating dosages up to a maximum of 1x1010 TCID50 with a constant localized radiation dose of either 20 Gy or 36 Gy. The principal investigator for the study was Dr. Kevin Harrington from The Institute of Cancer Research and The Royal Marsden Hospital, London, U.K.
Of the seven evaluable patients in the low-dose (20Gy) radiation group, two patients had a partial response ("PR") (esophageal adenocarcinoma and squamous cell carcinoma (SCC) of the skin) and five had stable disease ("SD") including patients with malignant melanoma, pancreatic adenocarcinoma, SCC of the larynx and SCC of the skin (2). In the high-dose (36Gy) radiation group, five of seven evaluable patients had PR (malignant melanoma (2), lung adenocarcinoma, colorectal adenocarcinoma, and ovarian adenocarcinoma) and two had SD (malignant melanoma).
The primary objective of the trial was to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), and safety profile of REOLYSIN when administered intratumourally to patients receiving radiation treatment. A secondary objective was to examine any evidence of anti-tumour activity. The treatment was well tolerated in all cohorts, with no DLTs, and no MTD was reached.
U.K. Phase I REOLYSIN in Combination with Docetaxel Clinical Trial
In 2010, a paper entitled "REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer," was published by Comins et al in the journal Clinical Cancer Research (Clin Cancer Res 16(22):5564-5572).
The paper reported final results from a combination REOLYSIN and docetaxel trial, designed to evaluate the anti-tumour effects of systemic administration of REOLYSIN in combination with docetaxel (Taxotere ) in patients with advanced cancers. Patients received docetaxel on day one (75mg/m2) and escalating doses of reovirus up to 3 x 1010 TCID50 on days one through five, every three weeks. The principal investigator was Professor Hardev Pandha of the Royal Surrey County Hospital, U.K.
Twenty-five patients were enrolled, with 24 being exposed to treatment and 23 completing at least one cycle of therapy. Sixteen patients were suitable for response assessment. The combination was deemed to be safe and well tolerated and a maximum tolerated dose was not reached. Antitumour activity was seen with one complete response (in the liver of a breast cancer patient with no evidence of disease recurrence at the end of the study, following eight cycles of treatment) and three partial responses. A disease control rate (combined complete response, partial response and stable disease) of 88% was observed. The authors concluded that the combination of reovirus and docetaxel is safe, with evidence of objective disease response, and warrants further evaluation in a Phase II study at a recommended schedule of docetaxel (75mg/m2, three times weekly) and reovirus (3 x 1010 TCID50, days one to five, every three weeks).
Eligible patients included those who had been diagnosed with advanced or metastatic solid tumours including bladder, lung, prostate or upper gastro-intestinal cancers that were refractory (had not responded) to standard therapy or for which no curative standard therapy existed. The primary objective of the trial was to determine the MTD, DLT, recommended dose and dosing schedule and safety profile of REOLYSIN when administered in combination with docetaxel. Secondary objectives included the evaluation of immune response to the drug combination, the body's response to the drug combination compared to chemotherapy alone and any evidence of anti-tumour activity.
Pre-Clinical and Collaborative Program
During 2010, the following article was published:
| Title | Senior Author | Publication | Description/Conclusion |
| "Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice" | Dr. Richard Vile Dr. Kevin Harrington | April 1, 2010 Journal of Clinical Investigation on | The research demonstrated that combining VEGF165 inhibitors such as Avastin or Sunitinib with systemic delivery of REOLYSIN leads to substantial regression and cure of established tumors in immunocompetent mice. This approach led to direct tumor cell lysis (break down) and triggered innate immune-mediated attack on the tumor vasculature. It also resulted in long-term antitumor effects, even against tumors in which viral replication was poorly supported. The authors concluded that because this combinatorial approach targets the tumor endothelium, these data have direct, wide-ranging, and immediate clinical applicability across a broad range of tumor types using reagents that are already approved for use in patients. |
Manufacturing and Process Development
In 2010, we completed the bulk production of two 100-litre cGMP production runs. As well, we finished the fill and packaging of the 100-litre cGMP production run that was completed at the end of 2009 along with the two production runs that occurred in 2010. Our process development activity in 2010 focused on process validation and formulation studies.
Intellectual Property
At the end of 2010, we had been issued over 250 patents including 40 U.S. and 11 Canadian patents as well as issuances in other jurisdictions. We also have over 200 patent applications filed in the U.S., Canada and other jurisdictions. We have an extensive patent portfolio covering the oncolytic reovirus that we use in our clinical trial program including a composition of matter patent that expires in 2028. Our patent portfolio also includes methods for treating proliferative disorders using modified adenovirus, HSV, parapoxvirus and vaccinia virus.
During 2010, we received cash inflow from financing activities of $27.3 million as follows:
Bought Deal Financing
In November 2010, we closed a bought deal financing whereby we issued 6,256,000 units at an issue price of $4.60 per unit for net cash proceeds of $26.8 million. Each Unit consists of one common share and one-half of one common share purchase warrant (each whole common share purchase warrant, a "Warrant"). Each Warrant entitles the holder to acquire one common share at a price of $6.15 at any time until November 8, 2012.
In December 2010, and in conjunction with the terms of our warrant indenture, we accelerated the expiry date of our U.S.$3.50 warrants issued in November 2009 to January 24, 2010. As of the end of 2010, we had received U.S.$0.4 million with respect to the exercise of 119,900 warrants.
Subsequent to December 31, 2010, we received U.S.$6.4 million from the exercise of 1,823,100 of our warrants with an exercise price of U.S.$3.50. As well, in February and March of 2011, we received proceeds of $8.2 million from the exercise of 1,322,750 warrants with an exercise price of $6.15. These warrants were issued in connection with the financing that closed on November 8, 2010.
During 2010, we received cash proceeds of $0.1 million with respect to the exercise of 32,433 stock options.
We estimated at the beginning of 2010 that our cash requirements to fund our operations for the year would be approximately $24 million. We amended our estimate during the year to $21 million due to the timing of patient enrollment in our Phase III pivotal trial. Our cash usage for 2010 was $18,033,732 from operating activities and $81,846 for the acquisition of property and equipment. Our net loss for 2010 was $19,973,772.
We exited 2010 with cash resources (cash, cash equivalents and short-term investments) totaling $42,905,928 (see "Liquidity and Capital Resources").
REOLYSIN DEVELOPMENT FOR 2011
Our planned development activity for REOLYSIN in 2011 is made up of clinical, manufacturing, intellectual property and collaboration programs. Our 2011 clinical program includes the anticipated completion of stage 1 (approximately 80 patients) of our Phase III head and neck clinical trial and commencement of stage 2. As well, we expect to commence enrollment in our colorectal study and complete enrollment in our non-small cell lung, U.S. phase II head and neck cancer trials and support those clinical trials that are sponsored by CTRC, Leeds and the NCI.
Our 2011 manufacturing program includes several 100-litre cGMP production runs along with the related fill, labeling, packaging and shipping of REOLYSIN to the various clinical sites. As well, we plan on performing smaller process development studies examining formulation, stability and additional scale up. Our intellectual property program includes filings for additional patents along with monitoring activities required to protect our patent portfolio. Finally, our 2011 collaboration program will finish the studies in place at the end of 2010 and contemplates the addition of future studies that may be required.
We estimate that the cash requirements to fund our operations for 2011 will be approximately $29,000,000 (see "Liquidity and Capital Resources").
CRITICAL ACCOUNTING POLICIES AND ESTIMATES