BioScience Biz

Biotech business development--pitfalls to avoid

Biotech business development teams are tasked with finding a partner—usually a large pharmaceutical or biotech company—that will in-license intellectual property. To do this properly, the team members must understand their asset's potential value, attract partners, effectively communicate the asset's value to these partners and eventually close an out-licensing deal on mutually beneficial terms.  By using the most effective methods in business development, teams will be able to present their product effectively to potential investors and partners, paving the way to success in the biotech market. Avoiding the seven deadly sins of business development will raise your company to a level of professionalism that pharmaceutical companies and investors expect from experienced partners. The seven deadly sins are just that—deadly. Avoiding them can bring your business development to life.

A thoughtful article recently written by Jeffrey J. Stewart and Ben Bonifant describes seven pitfalls to avoid when you search for a partner with which to further develop you budding biotech business.  They are a consultant and vice president, respectively, in the business development practice at the specialized management consulting firm Campbell Alliance in Raleigh, North Carolina.  During their years in the pharmaceutical and biotech sectors, they have worked with business development teams of dozens of life science companies.  So, they should know about biotech business development. Read their full article in Bioentrepreneur.

The stem cell frontier, 2008, on display, By Steve Clark

Cut a flat worm in two, the tail will grow a new head and the head a new tail. Cut it right down the middle, it will grow a mirror image. How does it know what to grow?

Flies can re-grow damaged tissues. Small fish can regenerate heart muscle. Why can’t humans?

In a developing infant, how do human embryonic stem cells know to grow into heart, muscle, liver, neurological and other cell types at the proper time and in the proper place?

These questions are at the center of science’s brave-new-world of stem cell biology and were the topic of the recent 3^rd Annual Stem Cell Symposium. The science was deep and detailed, and enormously enthralling. It was an intellectual playground of exciting ideas and fabulous potential.

The overriding lesson from the conference is that the mechanism by which stem cells regulate how and when they replenish themselves vs develop into different tissues is conserved in species as divergent as worms, flies, fish and mammals. This is fascinating for developmental biologists, but it also has a profound practical impact for eventually using stem cells to treat human disease. Let me explain how.

A primer on stem cell science

Consider for a moment what needs to be accomplished for an immature stem cell to differentiate into, say a beating heart cell. First, there needs to be a stimulus that initiates this program, telling the stem cell to specifically move along the cardiac muscle developmental pathway. The stem cell must then begin expressing heart cell genes while repressing the expression of all other genes that could cause it to become liver, blood, kidney and all other cell types. Quite a tall order!

Once the stem cell develops into a mature beating heart cell, it remains that type of cell. Mature cells, like zebras, cannot change their stripes. We never see a heart cell become a skin cell and vice versa. Cellular development is unidirectional and this has been one of the central tenants of developmental biology.

Then along comes Scottish scientist, Ian Wilmut, who did an experiment in the mid-1990s that no self-respecting developmental biologist would attempt since we all “knew” that cell development only moved in one direction.

What Wilmut did was to remove the nucleus from an egg cell and replace it with the nucleus from a fully mature cell taken from a different animal. Keep in mind that this donor nucleus had already been directed to express only those genes of the tissue it was taken from and to repress the expression of genes from all other tissues.

Wilmut then transferred this engineered egg into the womb of a pseudo-pregnant sheep, where the engineered egg should have died. Instead, a sheep was born that was a genetic twin of the nucleus donor sheep and the world was introduced to the first cloned animal, Dolly.

This is the type of research result that causes a scientific paradigm shift. For the first time, we realized that the genetic program of a fully developed adult cell, when placed in the proper environment, can be reprogrammed to relinquish its adult cell properties and return to its undifferentiated stem cell state, capable of developing into a fully grown sheep. 

Around the same time that Dolly was born, University of Wisconsin-Madison scientist, Jamie Thomson, published his seminal studies demonstrating the ability to grow monkey and human embryonic stem cells (or ESCs). These, of course, are the immature cells derived from five day old embryos that are able to develop into all tissues of the adult body. The way that ESCs are harvested kills these embryos making ESC research highly controversial. It would be great to be able to obtain such embryonic stem cells without having to destroy a functional human embryo.

Fast forward ten years to the conference where Professor Thomson gave an update on his recent report that he can reprogram adult cells to become stem cells without having to transplant cell nuclei. Looking at recent research from different labs, he noted that only a few regulatory genes are needed to maintain cells in their nascent developmental stage. As the research presented at the conference illustrated, these regulatory genes work across different species, so this mechanism is highly conserved in biology.

Thomson used routine gene transfer technology to induce expression of three different regulatory genes in the cells of mature fibroblasts and, amazingly, the mature cells were re-programmed to become stem cells! What Wilmut was able to do by transferring a cell nucleus to an enucleated egg can now be done in a petri dish and without the egg cell.

At the conference, Thompson explained that these “induced pluripotent cells” or iPCs seem to behave exactly like ESCs. Think about the implication of this observation: it means that mature cells from an adult can be re-programmed back to the stem cell state where they are able to generate anew, all tissues of the human body.

What next for stem cells?

UW-Madison stem cell researcher, Clive Svendson, moderator of the conference, believes that the next major advance will be the ability to develop iPCs by simply changing the environment in which adult cells are grown in the lab, which could be accomplished in about a year. This means that we would not have to insert several genes into a cell’s DNA, which has significant risks and is not a trivial procedure. Thus, it soon may be very easy to take cells from your skin, put them into a defined tissue culture environment and develop stem cells that contain your precise genetic makeup. No embryos would be destroyed and no clones would be created in the process, mitigating most of the ethical concerns.

Svendson opined that this could lead to a big boost in the tissue banking business as people store tissues when they are young for making stem cells if they should need them later. This would be necessary because, as Thomson explained, chronologically young cells are more efficient at being reprogrammed than cells from older animals. One can envision that it could become routine at birth to store placental tissue, the youngest tissue readily available that is genetically identical to the newborn baby.

As exciting as the science was at the conference, there remain some problems to deal with before these stem cells are used in the clinic. First, as with ESCs, undifferentiated iPCs form tumors called teratomas. Therefore, we need to develop a fail-safe way to completely separate or incapacitate contaminating stem cells from the functional tissues grown from them before we put them into patients. According to an article I posted here earlier, the FDA recently convened a meeting to grapple with this problem in anticipation that clinical trials will begin in the near future.

Next, even if we can use stem cells to regenerate damaged tissues, we still need to continue research into the causes of degenerative diseases because simply replacing the dying cells without dealing with what causes them to die may only be a short term fix.

Potential ethical issues may still arise

Finally, and potentially an explosive issue, there remains an ethical question regarding iPCs that no one seems to have addressed. When a mature cell is reprogrammed, how far back does it go? Do iPCs only have the potential to develop into different body tissues, or can an iPC, if given the chance, form an embryo? Of course, if the iPC cells are more like fertilized eggs than stem cells, then all bets are off--the ethical issues will arise again.

I asked both Svendson and Thompson about this and both admitted that this idea had not been tested. Svendson even owned up that no one in the field wants to test it. They do not want to know the answer because it could be very inconvenient.

My prediction

Carl Gulbrandsen, Director of the Wisconsin Alumni Foundation, shared with me that reading Thomson’s paper on reprogramming adult cells to derive embryonic iPCs made him “tingle”. Mr. Gulbrandsen does not seem to be the tingly type, but his response to Thomson’s results was not inappropriate—they are that amazing and significant.

As a scientist, I have learned to be cautious about making predictions. However, I venture one prediction here that I believe has a very good chance of being realized: Professor Jamie Thomson will, in the not-to-distant future, be awarded the Nobel prize for his outstanding work that has created a whole new field of stem cell biology and invigorated the practice of regenerative medicine. While I am at it, you can bet that he will share the prize with Ian Wilmut.

Any takers?
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This post was first published in-part by the Wisconsin Technology Network News

 

© 2008 Steven S. Clark, PhD. Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, Steven S. Clark, nor other authors, do not assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

Articles contained herein, are meant to be distributed freely to interested parties. However, any excerpts from any article must credit BioScience Biz.

FDA mulls embryonic stem cell therapy

It is not a matter of if, but of when clinical trials using stem cells to treat human diseases will begin. In anticipation of this, the FDA is considering ahead of time, what kind of oversight they will need to provide when the first clinical trial applications reach their door. Not bad, a government agency thinking proactively! Read on.

Posted on The Scientist NewsBlog by Andrea Gawrylewski

With biotech companies inching up on clinical trials for human embryonic stem cell-based therapies, the US Food and Drug Administration held a meeting yesterday to discuss scientific issues in properly deriving and characterizing the cells, as well as appropriate clinical trial monitoring.

Three biotechs, Geron Corporation, Advanced Cell Technology, and Novocell presented some of their scientific work on spinal cord injury, vision impairment, and diabetes, respectively, at the meeting. Geron and Advanced Cell Technology are hoping to begin testing therapies of cells derived from human embryonic stem cells sometime this year, according to Bloomberg News. Jane Lebkowski, senior vice president of regenerative medicine at Geron Corporation, told The Scientist she could not comment on whether this was true.

"The science was ready to have this kind of discussion, to make sure clinical trials are safe," Celia Witten, spokesperson for the FDA told a group of reporters after the day-long meeting, though she declined to say whether the agency has yet received any Investigational New Drug applications.

The advisory committee, which was made up of 25 independent scientists and FDA researchers, addressed issues of proper animal studies for preclinical testing and how researchers can control the embryonic stem cells for appropriate differentiation -- that is, so they don't form cancerous teratomas.

"There was a lot discussed in the range of things we're already thinking about," Lebkowski told The Scientist. "And several ideas we've been implementing already." Some of the committee's ideas were rather extreme, she added; some of the large animal model studies in non-human primates or pigs that the committee discussed were not very practical and extremely complicated -- the committee mused aloud whether allograft experiments (for example, pig embryonic stem cells transplanted to pig body) should be conducted before transplanting human embryonic stem cells to different species.

Several committee members noted that guidelines and requirements of human embryonic stem cell-based therapies will vary from disease to disease, and cell product to cell product. However, all the members seemed to agree that a common, standardized assay should be developed to determine the tumorigenicity of a specific cell product.

Kenneth Chein, from Harvard Medical School, noted that transplanting cardiomyocites and other types of differentiated embryonic stem cells has yielded mixed efficacy results so far, requiring that more definitive assays need to be developed for efficacy and safety.

The committee also addressed how researchers and clinicians will be able to control and monitor where the cells go once they are administered. While new technologies such as reporter genes may improve researchers' ability to track transplanted cells, some committee members questioned whether new techniques should be used at the same time as therapeutic embryonic stem cells, which itself is a novel type of therapy.

Some members of the committee said they were uneasy about embryonic stem cell therapies, and the committee discussed the potential of developing failsafe mechanisms in the cell products, like suicide genes. But some noted that such approaches may have their own therapeutic complications and risks.
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© 2008 Steven S. Clark, PhD. All Rights Reserved.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, Steven S. Clark, nor other authors, do not assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

Articles contained herein, are meant to be distributed freely to interested parties. However, any excerpts from any article must credit BioScience Biz.

Madison biotech company happy to ride the coattails of competitor, By Steve Clark

Madison, WI based Quintessence Biosciences is developing a cancer therapy that targets cancer cell RNA.  Since current cancer therapies target DNA or proteins,  this is a very novel approach to treating cancer.  While Quintessence plans to enter initial clinical trials this summer, its major East Coast competitor, Alfacell, has just finished its second Phase III trial on a similar product.  Read my column, Biotech Takes, to find out why Quintessence is enthusiastic about Alfacell's success.

A cancer vaccine is approved in Russia and investors are happy even if the FDA is not

Cancer vaccines have been very hard to come by. So when a New York-based biotech company, Antigenics, saw the results of its recent trial testing a vaccine for kidney cancer (Oncophage), enthusiasm was high. Even though the vaccine did not meet the primary end point of the trial, it did seem to work in a subset of the patients. But, the FDA, in its disputable wisdom, did not accept the finding and required the company to design and conduct a new Phase III trial. The company’s response? Get approval for the vaccine in Russia.

Could this be a new strategy for small biotechs?  Read the article below for more details.  

By Alla Katsnelson, April 9, 2008 on TheScientists.com NewsBlog

A New York-based biotech company announced today (April 8) that it has received approval for the first therapeutic cancer vaccine -- in Russia.  It is the first approval by a regulatory body of a cancer immunotherapy.

The therapy's approval in Russia won't in itself boost its chances for approval in the US or the EU, or improve the prospects of other cancer vaccines that are in the biotech pipeline, Ren Benjamin, senior biotech analyst at the New York investment firm Rodman and Renshaw told The Scientist. But Russia is "novel ground" for small biotech, he said: Seeking first approval in a country outside of the US and EU is a bold move, and both biotech companies and investors will be closely watching to see how lucrative a market Russia turns out to be.

The antibody-based therapy, Oncophage, received a registration certificate from the Russian Ministry of Public Health to treat a subset of kidney cancer patients who are at intermediate risk for disease recurrence, the company, Antigenics, said in a press release The treatment, made from patients' tumor cells, increased recurrence-free survival by 1.7 years according to the results of a phase III clinical trial, the release said.

Cancer immunotherapy has long been a field riddled with scientific challenges, and as we reported in 2006, Antigenics' vaccine was no exception. The company's phase III study in patients with nonmetastatic kidney cancer did not meet its primary endpoint, the company reported last year. Further analysis revealed that the treatment did seem to work for a subgroup of patients who had a lesser risk of recurrence. But such post-hoc analysis isn't enough for the FDA, which has already said that Antigenics needs to conduct a new trial looking explicitly at this patient group.

"I think that other (cancer vaccine) companies in the past -- main one being Dendreon -- have gotten phase III trial results that have shown promise in a subset of patients," said Benjamin. "However, no one has been entrepreneurial enough to seek registration in a country like Russia."

According to recent reports, he noted, the pharma market there is growing astronomically. "This will really be a landmark analysis -- not only to see whether small biotechs can do it alone in these other countries, but also, are these other countries worth pursuing," he said.

Meanwhile, Christopher Wood, a cancer researcher at MD Anderson Cancer Center who led the Oncophage trial, told CNBC that the company had assured him they plan to use proceeds from Russian sales to fund a study for FDA approval. Wood also noted that the data has been submitted for publication. (Wood wasn't available to comment by the time I posted this blog.)

Antigenics is also looking into approval in the European Union based on its current data.
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Further comments on the FDA’s response to Antigenics’ vaccine trial can be found on BiotechBlitz (April 10, 2008).
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© 2008 Steven S. Clark, PhD. All Rights Reserved.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, neither Steven S. Clark, nor other authors,  assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

Articles contained herein, are meant to be distributed freely to interested parties. However, any excerpts from any article must credit BioScience Biz.