BioScience Biz

FDA increases new drug approvals, but take a closer look

The FDA has approved 29 new drug applications (NDAs) through April, 2008.  This represents the highest NDA approval rate since 2000.   Last year, the FDA approved only 16 NDAs and the 10-year average is 24.  Good news for the pharma industry?

Maybe not.  10 of the 29 new approvals come from new manufacturers for existing drugs, approvals of drugs already marketed or new formulations of existing drugs.  In other words, only 19 new pharmaceutical drugs made it to to the market last year, compared to 13 a year ago.

New Molecular Entities (NMEs), or compounds that are not related to any existing drug, is a better measure than NDAs of new classes of therapeutics entering the marketplace.  NMEs represent entirely new drugs and treatment opportunities.  In the past year, only three NMEs were approved, matching the previous low mark reached in 2002.  Over the last ten years, the average NME approval rate was six per year.

FDA delays embryonic stem cell clinical trial

 Geron Corporation, the Menlo Park, California-based company had sought permission from the U.S. Food and Drug administration to begin a human trial to test its GRNOPC1 stem-cell compound in patients with spinal cord injuries. In a press release dated yesterday, Geron anounced that they received oral notice from the FDA had delayed the Investigational New Drug application the company filed in order to begin clinical trials.  This delay does not mean that the IND was rejected, but until Geron receives the official letter, it will not known why the application was delayed or how long it will take to rectify the issues the FDA has.

Geron worked with the FDA over the last four years leading up the filing of a 21,000-page IND application.  Read the full press release here.

Madison's stem cell frontier, By Steve Clark

In an earlier column about the recent Stem Cell Symposium held on the Promega Campus, I extolled the exciting frontier of stem cell basic science that was on display; however, it was just as interesting to catch up with local stem cell researchers who attended the Symposium. I caught a glimpse of the current status of stem cell science in the Madison area.

Other health benefits of embryonic stem cells

For instance, I ran into Tim Kamp, an MD in the UW-Madison Department of Cardiology who, along with Professor Jamie Thomson, recently developed a reliable way to derive human heart cells from embryonic stem cells (ESCs).

About four years ago I first met Kamp in his UW-Madison office to learn about his research. At that time, researchers knew that when given the chance, human ESCs haphazardly differentiate in tissue culture into all the different tissue types and Kamp, using a microscope, had been able to find among the clutter of different cells a few well developed heart cells that actually were beating! You can see a short video clip of one of the beating heart cells here.

Using a steady-handed robot, Kamp inserted a very fine probe into a beating heart cell and measured its depolarization or the exchange of ions across its membrane, which constitutes the electric current that causes heart muscle to beat. With this, he recorded an “EKG” on a single human heart cell that changed as expected when he added to the culture, a drug often given to heart patients.

Currently, animal models are the best way to measure pharmacological effects of drugs on the heart—an important but insufficient model since 30% of drug failures are due to cardiotoxicity. Clearly, we need ways to test drugs on human heart cells, but until the advent of ESCs, there was no reliable way to obtain and grow them in the lab. Now, being able to derive functional heart muscle cells from ESCs provides a important option for testing drugs on real human heart tissue, thereby improving the safety and efficacy of new drugs. At least this was Kamp’s goal four years ago when I talked with him in his office.

Things seem to be progressing well. A couple of years ago, Kamp and his co-workers launched the local biotechnology company, Cellular Dynamics International, in order to bring this technology to fruition. In early March, Roche Palo Alto reached an agreement with CDI to begin using their ESC-derived heart cells for testing the cardiotoxicity of candidate drug compounds.

Using ESCs to derive fully functional mature cell types for testing potential drugs and toxins directly on human tissues is an under-appreciated and poorly communicated application for ESCs, but one that will soon be widely employed in the pharmaceutical industry. Thus, human ESCs will likely play an important role in human health, even if they are never used to directly treat human disease.

Kamp indicated that similar screening methods are being developed for other tissue cell types derived from human ESCs.

Treating neurological diseases

A few years ago, I attended a seminar by UW-Madison neuroscientist, Clive Svendson, who showed a video clip of patients with Parkinson’s disease before and after treatment with a nerve cell factor known as GDNF. The result was a dramatic slowing of disease progression in treated patients.

As encouraging as this therapy was, it remains highly experimental since GDNF cannot cross the blood-brain barrier and must be delivered by cannula—a thin tube inserted deep into the brain area affected by Parkinson’s disease—not an attractive long term option.

Furthermore, GDNF therapy only retards the progressive loss of dopamine producing neurons that is characteristic of Parkinson’s disease; it does not reverse the process. Therefore, this will not likely benefit patients with advanced disease who have lost too many of these critical cells. This is where the hope of stem cell therapy merges with the other great therapeutic hope—gene therapy.

For instance, ESCs alone are not likely to be much of a benefit for patients with Parkinson’s, because stem cell-derived dopamine-producing neurons transplanted in the brains of Parkinsonian patients likely will suffer the same fatal fortune as their endogenous predecessors. But, combine stem cell regeneration of the neurons with in situ production of GDNF via gene therapy technology and you just may be able to sustain dopamine-producing cells for the long term. Or so the hope goes.

A similar idea is being tested in Svendsen’s lab for treating amyotrophic lateral sclerosis; also know as ALS or Lou Gehrig’s disease. Like Parkinson’s, ALS is caused by the progressive and irreversible loss of certain critical neural cells in the brain. Svendsen’s lab has developed rat and primate models of ALS and using human fetal-derived neural stem cells, in conjunction with gene transfer technology, have successfully implanted fully functional, GDNF producing neurons in brains of these ALS animals. The results are very encouraging at this point--they see long-term survival of the transplanted cells and sustained production of GDNF, and these correlate with resolution of symptoms.

This is not the first example using ESCs to successfully treat human diseases in animal models, but ESCs have not yet made it into the clinic. Human trials will likely begin in the next year or two and the FDA is now considering how to best monitor them for safety and efficacy--not a trivial undertaking, but, stay tuned.

Moving stem cell science along

At the symposium I also had the chance to connect with Eric Forsberg, the recently appointed Director of WiCell. This is the non-profit spin-off from the Wisconsin Alumni Research Foundation (WARF) that provides support for stem cell researchers at UW-Madison.

According to Forsberg, WiCell, not only maintains the National Stem Cell Bank, it also engages in outreach activities and provides core services for stem cell researchers that are not found elsewhere on the UW-Madison campus. Forsberg pointed out that WiCell is also happy to provide such support and training for private stem cell companies in order to foster the development of cell-based medicine in Wisconsin..

Forsberg hopes to soon partner with the Waissma Center on the UW-Madison campus to begin a trial run to grow clinical-scale batches of ESCs under the cGMP conditions that are required in order to use the cells to treat patients. The Waissman Center has the cGMP facilities to produce biological materials for clinical use.

This will be a proof-of-principle endeavor designed to show that ESCs can be produced in clinically relevant quantities while maintaining their state of differentiation. Unforeseen problems, the bane of any biotechnology research, will be identified and resolved during this trial run so they will be ready when the time comes to quickly move ESCs into clinical trials.

We rapidly approach the day when ESCs will be used in experimental therapies of human diseases. Probably the first trials will use blood or bone marrow products derived from ESCs as a donor source for marrow transplantation or red cell transfusion.
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© 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 the BioScience Biz Blog.

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.

Predicting success in emerging biotechnology, Part 2. By Steve Clark

An investor recently asked me to compare the technology behind two early-stage biotech companies he was thinking of investing in. Both companies had novel therapeutic products at similar stages of development and the investor wanted to know which company’s product had the greater chance of success.

In an earlier article on this topic, I cautioned that predicting success of a technology is impossible. Therefore, in my analyses, I look for scientific limitations that might portend failure of a new technology.

Here, I illustrate another way to evaluate emerging biotechnology—science-focused market analysis. I contend that one needs to assess the market, not only from a business perspective, but also with a scientifically critical eye in order to fully appraise the risks of a new technology. Let me use a real example to illustrate how this works.

Two companies, A and B, are at similar stages of developing novel therapies for treating cancer of the prostate (CaP). Prostate cancer is very difficult to treat successfully; hence, enormous efforts are underway to develop better therapeutic options. The competition is stiff.

In order to fully appreciate the market potential for these products, we first need to understand the biology and treatment of CaP.

Treatment options are limited for CaP 

When CaP is detected, usually surgery or radiation is used first to reduce the size of the cancer (step 1 in the figure). At this stage, cancer growth depends on androgens, or male hormones produced in the testes; therefore, after surgery or radiation, men are often chemically castrated in order to retard the re-growth of any remaining cancer cells (step 2 in the figure). Despite this treatment, the cancer invariably returns and slowly progresses to a more aggressive malignancy.

CaP progression obviously means that androgen depletion no longer prevents the tumor from growing. The first indication of cancer progression is increasing blood levels of PSA (prostate specific antigen), a protein which is secreted by prostate cells. At this stage in the disease, there is no therapeutic option and one simply waits (“watchful-waiting”, step 3 in the figure) until the slowly re-growing cancer develops into end-stage carcinoma (step 4). Increasingly, patients with end-stage CaP are treated with chemotherapy, but this offers minimal, if any, results.

Experimental therapies of the two companies

Because CaP is so difficult to treat, many experimental therapies are in various stages of development and mostly target the end-stage metastatic disease. It is in this milieu that companies A and B are working to develop new therapies.

Company A is developing a naturally occurring biological product that enters cells and kills them by preventing gene expression. For unknown reasons, the product selectively kills advanced-stage cancer cells and not normal cells. Therefore, this product is targeted for potential treatment of end-stage CaP.

This experimental product has stiff competition from the plethora of other experimental cancer therapies under development. Nevertheless, it is likely that multiple therapies that have different mechanisms of action will be needed to successfully treat end-stage CaP. This means that the uniqueness of Company A’s product is a significant advantage; however, the stiff competition also means that, in order to marketable, this product will need to show as good or better efficacy and side-effects than other current and emerging therapies.

Company B has two novel therapies in development. The first therapy is derived from a natural dietary product that surprisingly blocks the androgen receptor. This drug is targeted toward prostate cancer patients who have undergone androgen deprivation therapy, but show rising PSA levels without having yet developed androgen-independent metastatic cancer. Currently, “watchful waiting” (step 3) is the only clinical option available for these patients. So, this product is designed to throw another punch at the slowly growing cancer before it achieves full blown androgen-independence.

The second product that Company B is developing is based on careful understanding of the cell biochemistry that drives CaP progression. When androgen binds to its cellular receptor, many things happen in addition to stimulating growth of prostate cells. It is believed that a specific “side-activity” of androgen stimulation is responsible for turning normal prostate cells into cancer cells. Furthermore, this side-activity also likely drives the progression of CaP from a slow growing tumor to end-stage cancer.

Company B’s second product blocks this cancer-inducing side-activity without affecting any other activity of androgen stimulation. For this reason, the drug is targeted for patients who have not yet undergone androgen depletion therapy. The goal is to retard early tumor progression and avoid the androgen depletion regimen which comes with considerable side-effects.

Which technology do you invest in?

All things being equal (or at least as much as possible between two different early-stage biotech companies), the decision comes down to predicting which technology has a better chance at success, or as I wrote previously, the least chance of failure. Here, science-focused market analysis tells you that the product under development by Company A, while unique and with good potential, nevertheless will compete with current therapies as well as with the many new experimental therapies in development.

In contrast, the products being developed by Company B specifically target stages in CaP where there is no good therapeutic option currently available. The competition for these products is negligible, which means that even if they are marginally effective or have side effects, there likely will be a significant market for them.

The unique biomedical niche targeted by company B’s products means that the significant risk factors company A faces due to competition are not likely to be a problem for Company B. Hence, market analysis through a scientific lens favors investing in company B over company A.

The example described here provides a good illustration of how scientific understanding of emerging biotechnology can add significantly to your market analysis. So, don’t forget to include your technical advisor when doing market research.

This article was first published in part in the Wisconsin Tecnology Network News
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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.

 

Paths to entrepreneurship in the life sciences

A thoughtful article by Shreefal Mehta identifies and describes two types of life science entrepreneurs. The first type, called the "technopreneur", is familiar to most of us. This is a university based scientist who has a potentially marketable idea/product, has it patented, assumes the license from his university, finds collaborators and investors and works to launch the venture. However, this traditional entrepreneurial path is not the exclusive route to life science venture creation. 

Mehta, who is from the Lally School of Management and Technology at the Rensselaer Polytechnic Institute, points out the value of social networks that fuel serendipitous associations that can lead to the development of new businesses via unconventional routes. In other words, it is not always technical savvy that drives bioscience ventures, but sometime it is your chance associations and insights into market needs. Mehta uses several short examples to illustrate alternative paths to venture creation in the life sciences by people he calls, “market perceivers”. 

He concludes that, “A technopreneur might have difficulty in taking on all of the positive aspects of a market perceiver's aptitude, skills and mental processes, just as a market perceiver might find it difficult to evaluate and determine technical milestones, capabilities and limitations.”

Read the full article here.