Replies to post #49524 on Biotech Values

[DewDiligence]

Apo A1 Quiz (not to be answered by anyone
who listened to today’s SemBioSys webcast):

Who owns the patent on the Apo A1 and Apo A1 Milano molecules?

[DewDiligence]

Safflower Seeds Sowing a Protein-Producing Future

[More on the SemBioSys story.]

http://us-pharmatechnologist.com/news/ng.asp?n=78254-sembiosys-pfizer-safflower-seed-lines-transgeni...

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By Katrina Megget
17-Jul-2007

The humble safflower seed is looking like it could be the next protein-producing factory after SemBioSys Genetics produced commercial levels of an atherosclerosis treatment.

The Canada-based biotechnology company has successfully modified safflower seed lines, and expressed and collected apolipoprotein A1 and its variant apolipoprotein A1 (Milano), collectively referred to Apo A1,which is a next-generation cardiovascular drug that targets the removal of atherosclerotic plaque from arteries.

The development represents a move into the $35bn cardiovascular drug market, but the seed lines have also proved successful in producing about 43 other therapeutic proteins at a fraction of the cost of conventional methods, SemBioSys chief scientific officer Dr Maurice Moloney told US-PharmaTechnologist.com.

The transgenic technology, which is looking as an increasingly popular tool for producing proteins, was the brainchild of Moloney, who developed the genetically modified "Roundup Ready" crops. [Roundup Ready is the hugely successful line of GM crops from Monsanto that are resistant to treatment with the Roundup herbicide.]

In the safflower seed case, the Apo A1 gene is only expressed in the seed. The technology, which can be used in any oil seed, has been further developed so that the protein attaches itself to oil bodies in the seed making the recovery of the protein much easier as the oil floats out of the solution when the seeds are crushed to extract the protein.

"This dramatically reduces the cost of purification," Moloney said.

The company decided to focus on safflower because it was a less common crop, compared to canola, so it was easier to biologically isolate the crop reducing the chances of cross pollination or the accidental mixing of seeds with non-transgenic ones, he said.

Meanwhile, developing the seeds as the protein-producing factories instead of another part of the plant, meant the company could utilize the long-term storage capabilities that seeds have as well as being able to adjust production of the protein depending on the market demand.

"This is difficult to do if you are dealing with conventional methods like fermentation," Moloney said.

The cost advantages were also very promising over conventional methods, he said.

The cost to grow a ton of seed, about an acre of safflower which would then produce about 2kg of Apo A1, would be about $800. This is compared to the current cost which sits in the range of about $400 per gram of Apo A1.

Moloney estimated the technology could be developed to reduce the cost by 90 per cent. As a result, the safflower seed technology would be particularly beneficial in the production of Apo A1, as large amounts of the protein were required for treatment, he said.

SemBioSys president and chief executive Andrew Baum said in a statement: "We believe manufacturing capacity and cost are major commercialization issues for pharmaceutical companies developing Apo A1. Today's announcement demonstrates that safflower seed is an enabling production vehicle for Apo A1 with the scale and economics necessary to allow for commercialization of this potentially transformative therapy."

Apo A1 has been described as a promising new therapy for the treatment of cardiovascular disease. It is the major component of the good cholesterol, high density lipoprotein (HDL), which naturally removes atherosclerotic plaque from arteries.

Currently, Pfizer is developing Apo A1 via E.coli, with positive clinical trial results, while CSL and Borean Pharma have both recently confirmed the strong therapeutic potential of their respective Apo A1-based drug candidates, CSL-111 and Trimeric Apo A-I, in clinical and preclinical trials.

SemBioSys intends to scale up production of safflower-produced Apo A1 and perform the necessary preclinical work in 2008 in order to initiate clinical trials in 2009.

The company has also produced authentic human insulin in safflower, which is expected to enter clinical trials in early 2008.

SemBioSys is now planning to initiate development program partnerships.
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[DewDiligence]

SemBioSys Updates Apo A1 Development Program

[Oops—commercial expression levels of Apo A1 Milano have been realized but (contrary to what was stated in the company’s 7/12/07 PR) commercial levels of native Apo A1 have not.]

http://biz.yahoo.com/prnews/070822/to265.html?.v=56

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Wednesday August 22, 7:00 am ET

- Canadian Biotechnology Company confirms commercial expression levels of Apo AI Milano variant and clarifies status of native Apo AI -

CALGARY, Aug. 22 /PRNewswire-FirstCall/ - SemBioSys Genetics Inc. (TSX:SBS), a biotechnology company developing a portfolio of therapeutic proteins for metabolic and cardiovascular diseases, today updated a release issued on July 12, 2007 announcing that the Company had achieved commercial levels of apolipoprotein AI (native Apo AI) and apolipoprotein AI(Milano) (Apo AI Milano) accumulation in safflower seed lines. SemBioSys has confirmed in multiple assays that it has developed commercial levels of Apo AI Milano in safflower seed lines. Based on further evaluation of the existing data from native Apo AI safflower seed lines, the Company must clarify that, to date, it has not proven it has achieved commercial levels of native Apo AI accumulation in safflower.

While the assays demonstrate that native Apo AI accumulates in safflower, the commercial level threshold set by SemBioSys of 1% total seed protein expression has not yet been attained. Over the coming months SemBioSys will continue to analyze the additional safflower seed lines it currently has in development. The Company expects that the analysis of these seed lines will be complete by the end of the fourth quarter of 2007.

"While this is a setback to our native Apo AI program, we believe it is temporary in nature. Our success with the Milano variant has given us confidence that similar accumulation levels will be found among the remaining native Apo AI plant lines we have created. We successfully achieved the commercial threshold for Apo AI Milano early in our current series of seed lines. We initially believed we had achieved a similar outcome in an early seed line from the native Apo AI series. We are currently, and will continue, analyzing new seed lines between now and the end of 2007 as they become available," said Andrew Baum, President and CEO of SemBioSys Genetics Inc. "In the meantime, we will continue to scale-up the successful Apo AI Milano seed lines to allow us to initiate animal trials with this material as soon as possible."

SemBioSys expects to receive in vivo efficacy results from animal trials for Apo AI produced in its model plant system, Arabidopsis, before the end of 2007. The Company is currently scaling up safflower-produced Apo AI Milano in order to initiate preclinical animal trials as soon as sufficient material is available.

The Company currently intends to partner one, or both, of the native Apo AI and Apo AI Milano programs prior to or shortly after Phase I clinical trials in 2009. SemBioSys believes its proprietary oilbody-oleosin production system offers the potential to overcome the manufacturing cost and capacity challenges of traditional fermentation-based technologies that have impeded the commercial development of Apo AI.

About Apo AI

Apo AI is a developmental-stage cardiovascular therapy, designed to rapidly stabilize and diminish atherosclerotic plaque for the prevention and treatment of cardiovascular disease. Apo AI is the major apolipoprotein associated with HDL, commonly referred to as "good cholesterol", which naturally removes plaque from arteries. Apo AI Milano is a natural variant of native human Apo AI characterized by a single amino acid substitution in its primary structure. In an epidemiological study, Apo AI Milano appears to confer enhanced resistance to atherosclerosis, suggesting that it may offer clinical advantages in the treatment of cardiovascular disease.

In a six week clinical trial, Esperion Therapeutics (acquired by Pfizer in 2003) demonstrated that its Apo AI Milano variant/phospholipid formulation could reduce plaque volume at a level and speed of atherosclerotic regression unattainable with any current drug therapy. Similarly, both CSL Limited and Borean Pharma A/S have more recently confirmed the strong therapeutic potential of their respective Apo AI-based drug candidates (CSL-111 and Trimeric Apo A-I) in clinical and preclinical trials.

High dosing (up to 20 grams per course of patient treatment) coupled with a large patient population is expected to drive volume demand of several tonnes of Apo AI per year, underscoring the value of a highly scalable plant manufacturing solution.

About Cardiovascular Disease

Atherosclerotic cardiovascular diseases are the leading cause of mortality in developed nations and by 2010 are projected to become the leading cause of mortality worldwide. In the United States coronary heart disease and stroke account for 70% of cardiovascular-related deaths, which claims more lives each year than the next four leading causes of death combined (cancer, respiratory disease, accidents and diabetes). Drugs positioned in the cholesterol and triglyceride management market are the single largest class of prescription pharmaceuticals, with global sales exceeding US$35 billion in 2006.

About SemBioSys Genetics Inc. (www.sembiosys.com)

Calgary, Alberta-based SemBioSys Genetics Inc. is a biotechnology company developing protein-based pharmaceuticals for metabolic and cardiovascular diseases. The Company's lead pharmaceutical candidates, produced in the plant host safflower, are recombinant human insulin to serve the rapidly expanding global diabetes market and Apo AI, a next generation cardiovascular drug. In addition to its pharmaceutical products, SemBioSys is developing a series of non-pharmaceutical products addressing human topical, nutritional oils and animal health markets.
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