Argenta Discovery Limited, the respiratory drug discovery and development company, announces a major milestone in its joint programme with AstraZeneca aimed at identifying improved inhaled bronchodilators to treat chronic obstructive pulmonary disease (COPD).

This important milestone marks the first candidate drug from the collaboration to enter Phase I safety and tolerability studies. This drug candidate is on track to enter Phase II ‘proof-of-concept’ trials later this year.

The original agreement between the two companies was announced in January 2007. Scientists from the two companies are collaborating to identify long-acting muscarinic (M3) antagonist (LAMA) and dual-acting muscarinic antagonist-?2 agonist (MABA) candidate drugs. These compounds will be developed as once-daily, inhaled mono or combination therapies. AstraZeneca will be responsible for the development and worldwide commercialisation of products arising out of the collaboration. Dependent upon success, Argenta is eligible for further development, regulatory and sales milestone payments. Royalties will also be payable to Argenta.

Commenting on the progress, Dr. Christopher Ashton, Argenta Discovery’s CEO, said, “The programme continues to deliver beyond the expectations of both parties and we are firmly on track to achieve our joint strategic goals for the programme.”

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow obstruction that is progressive and current therapies, including inhaled corticosteroids, fail to treat disease progression. COPD is a leading cause of morbidity and mortality worldwide with an overall prevalence in adults over 40 years currently estimated at between 9 and 10%. Unlike many other major diseases, deaths due to COPD are increasing and the World Health Organisation (WHO) estimates by 2030 that COPD will be the third leading cause of mortality and fifth leading cause of morbidity in the world. Thus there is a high level of unmet medical need for this progressive and debilitating disease.

About Argenta Discovery

Argenta Discovery was founded in August 2000. Argenta has expertise in chronic respiratory diseases, including Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. The company has generated a portfolio of pre-clinical bronchodilator and anti-inflammatory programmes with the goal of demonstrating clinical proof-of-concept. In 2009, Argenta completed its first Phase II clinical trial with ADC4022, an investigational medicine for the treatment of Chronic Obstructive Pulmonary Disease (COPD) and severe asthma.

Argenta also has a contract research division that provides integrated drug discovery services to a range of leading pharmaceutical and biotechnology companies worldwide. Argenta employs approximately 160 people and is based in Harlow, Welwyn Garden City and Slough, UK. For more information about Argenta Discovery, please visit www.argentadiscovery.com

Source
AstraZeneca

Researchers in London have demonstrated the ability of adult stem cells from bone marrow (mesenchymal stem cells, or MSCs) to deliver a cancer-killing protein to tumors.

The genetically engineered stem cells are able to home to the cancer cells, both in culture and in mouse models, and deliver TNF-related apoptosis-inducing ligand (TRAIL), destroying the tumor cells while sparing normal cells.

The research will be presented on Tuesday, May 19, at the American Thoracic Society’s 105th International Conference in San Diego.

“Present oncological therapies are limited by host toxicity,” said Michael Loebinger, M.D., M.A, who, along with S. M. Janes, M.D., Ph.D., conducted the research at the Centre for Respiratory Research at the University College of London. “They are also limited by cancer resistance and may not destroy cancer stem cells.”

With these experiments, the investigators combined two disparate areas of research that they believed held promise for treating cancer. Studies had shown that MSCs can be used as vectors to deliver anti-tumor therapy, while other studies found that TRAIL killed cancer cells, but not normal cells.

For their experiments, Drs. Loebinger and Janes identified those cells likely to be resistant to therapies (cancer cells that have characteristics of stem cells) and found that they were just as likely to be destroyed as tumor cells by this novel therapy.

In culture, the stem cells caused lung, squamous, breast and cervical cancer cells to die (all p<0.01), even at low stem cell/tumor cell ratios (1:16).

In mice, the researchers showed that the stem cells could reduce the growth of subcutaneous breast tumors by approximately 80 percent (p<.0001). The stem cells could also be injected intravenously as therapy for mice with lung metastases and could eliminate lung metastases in 38 percent of mice compared to control mice, all of which still had metastases (p=0.03).

It is the first study to intravenously introduce MSCs that have been genetically modified to deliver TRAIL. Drs. Loebinger and Janes chose the breast cancer cells for both models because in their in vitro experiments, the MSCs “demonstrated a particularly strong homing to breast cancer cells.”

“Breast cancer tumors are a good model of metastases,” added Dr. Loebinger, “but our plan is to test the engineered stem cells with other models, including lung cancer.”

While not fully understood, Dr. Loebinger added, the homing of the engineered cells appears to be a characteristic of MSCs themselves.

The authors conclude that, “this is the first study to demonstrate a significant reduction in tumor burden with inducible TRAIL-expressing MSCs in a well-controlled and specifically directed therapy.”

They believe that human trials of TRAIL-expressing MSCs could begin in two or three years.

Funding for this research was provided by the Medical Research Council UK.

Source: American Thoracic Society (ATS)

OGX-011 survival benefit: an even better Hazard Ratio.

With the release of ASCO abstracts last night we saw additional data and statistical analyses from OGXI’s Phase II trial. This was a randomized, controlled Phase II trial in prostate cancer with their lead compound OGX-011, that had shown a 10.6 month survival advantage, including a new multivariate analysis and hazard ratio. Until last night the hazard ratio, (a statistical measure of how much good or harm a treatment does to a patient) the company had presented was 0.6, i.e. patients treated with OGX-011 plus docetaxel had a 40% reduction in their death rate versus patients that only received docetaxel. Last night, in the more mature data, this impressive HR of 0.6 was not only maintained, but also further reduced to 0.54, which translated to a further reduction in the death rate to 46%. To put this into context: the hazard ratio for Dendreon’s (DNDN Market Outperform) Provenge’s successful Phase III trial was 0.775, or a 22.5% reduction in the death rate. To take this interpretation a step further, treatment with OGX-011 cut the death rate that Provenge’s impressive data demonstrated by half.

A look at Hazard Ratios (HR) and Survival Benefits and a caveat:

1) HR: Provenge 0.775 (22.5% reduction in death rate), OGX-011 0.54 (46% reduction in death rate), or OGX-011’s death rate is half of what it is for Provenge.

2) Survival benefits: Taxotere 2.4 months, Provenge 4.1 months, OGX-011 10.6 months, Abiraterone: has not been demonstrated that it has a survival benefit, just PSA declines, MDV3100: has not been demonstrated that it has a survival benefit, just PSA declines

3) A Caveat on Survival Benefits and HR: Taxotere’s and Provenge’s survival benefits were from large Phase III trials, while OGX-011 comes from a randomized, yet smaller, Phase II trial of 82 patients

Five points of comparison with Cougar (CGRB Market Perform), a company that also has Phase II data and is trading at an EV of $620M:

1) Abiraterone is about one year ahead in development than OGX-011, and 2) Abiraterone is an oral agent, vs. OGX-011 which is IV, but 3) the two drugs would not compete head-to-head with each other, since Abiraterone is oral and mostly going after an earlier patient population, while OGX-011 will be used together with Taxotere, and patients would have to go to their oncologist’s office to receive their chemo treatment anyway. 4) In addition, Abiraterone has only shown a reduction in PSA levels and not a survival benefit, and 5) its data are all from single-arm studies, while the OGX-011 data come from randomized, controlled studies

A word on Abiraterone, Valuations and Market Inefficiencies:

We believe Abiraterone has shown an impressive efficacy and safety profile and could end up being a clinical and commercial success. We are not trying to imply that one compound is better than the other. We are simply pointing out a major inefficiency in the market (due to the lack of investor awareness for OGXI), that we believe has lead to a disconnect and imbalance between the two companies’ valuations, which we believe represents an opportunity for investors to benefit from. We are not arguing that CGRB should not be where it is in terms of valuation; we are arguing that OGXI should be trading significantly closer to CGRB’s valuation than where it is currently trading.

Source
ASCO

View drug information on Taxotere.