PDI Blog

Are the FDA Regulations for Nucleotides Different than for NCEs?

Wed, 02 May 2012 14:39:00 GMT

The field of nucleotide-based therapies continues to make progress. Several products have already gained FDA approval including Macugen TM (Pegatinib), a PEGylated aptamer for wet age-related macular degeneration (AMD). Many more are in late stage clinical trials. Regulatory requirements may differ for these different types of drugs compared to what is required for an NCE. The main challenge is targeting the delivery which may require the use of nanoparticles or lipid formulations, or attaching a carrier molecule such as a virus, antibody or peptide. When assessing the safety of a nucleotide-based therapy, both the delivery vehicle and the nucleotide product itself have to be evaluated.

A White Paper written by Dr. Laura Hales explains the differences between nucleotide-based drugs and NCEs that should be considered during the pre-clinical stages prior to an IND filing. You can read the complete article, Regulatory Requirements for Nucleotide-Based Therapeutics, at our Resource Center.

New Patents for Old Drugs using Formulation Development and PK Modeling

Fri, 27 Apr 2012 14:35:00 GMT

As big pharma increasingly looks to biotechs to fill their pipelines, biotechs are looking for new ideas and therapies. Many have discovered new uses for existing drugs that are off patent. The advantage of using drugs that have an extensive safety history is often outweighed by the lack of patent protection. A good approach to bridge this gap and to generate new patent claims is to combine formulation development with PK modeling and find unprecedented solutions to existing therapeutic problems. A recent press release describes a renewed emphasis on these techniques.

Injecting Amorphous Dispersions

Mon, 23 Apr 2012 18:30:00 GMT

Is there a way to apply solid amorphous dispersion technology to injectables? Bruce Rehlaender thinks there is. He has written a White Paper entitled “Injecting Amorphous Dispersions” that can be downloaded from our Formulation Development web page.

Bruce talks about the techniques of creating solid amorphous dispersions suing polymers and a rapid solidfication process. He goes into describing how solids certainly can be used in subcutaneous and intramuscular injectables. While this is typically done to slow down release, it might also be used to enhance release. Bruce explains how a form of solid amorphous dispersions called solid lipid nanoparticles (SLNs) could be used in injections.

Is there more creativity in biotechs or in large pharma?

Fri, 20 Apr 2012 14:02:00 GMT

In a recent Blog by at LifeScienceVC, Bruce Booth comments on the poor R&D productivity at big pharma. He makes a point that the problem lies with the culture in these companies. He cites the “Tyranny of the Committee”, “Stagnation through risk avoidance” and the negative impact of the organization’s entropy.

I couldn't agree more with the thesis that innovation has been hurt in the large pharma companies because of their culture. I think that for creativity to flourish, creative scientists need time and space unencumbered by extraneous requirements and duties. Bureaucratic infrastructure has to be kept outside their realms so there are no limitations to their time and thoughts. They must be free to let their minds roam and then put ideas into motion to see if they are realistic. They must approach problems with the expectation that many solutions will fail before one will succeed. Their ability to create must be matched with their ability to allow others to process their discoveries into practical products.

One of the consequences of the tremendous success of pharmaceuticals is that large pharmaceutical companies have become behemoths. These large companies propagate the belief that they can only stay competitive by consolidation and growth. Companies that have full pipelines are bought out or merged with companies that have cash, but insufficient products to develop. This is not bad. The special expertise these companies have is the development of global products that require huge investments or people and money to run international clinical trials. Their over-sized bureaucracy is necessary to keep multiple large programs in motion.

However, virtual biotech companies can avoid the traps of bureaucracy and risk aversion. These small companies have a better opportunity to be the source of inventions that will continue the growth of our industry. These companies are typically nimble, flexible and able to allow their scientist the freedom to create. Often their creative thinkers are their founders so they propensity to invent is even more intense. This environment allows the freedom for creativity without the restrictions that large pharmaceuticals companies are likely to impose.

There is a more complete article on this topic entitled "Unbridled Creativity Abounds in Biotechs" in the White Papers section of the Resource Center.

Can we lower costs in Biotech R&D?

Tue, 27 Mar 2012 14:51:00 GMT

According to a recent Life Science Venture Blog posting by Bruce Booth, average exits for venture backed biotech firms has been around $150-$175M. Less than 10% of the exits are over $400M and only a handful have been above $1B. The takeaway is that biotechs are more likely to have a small exit than large which puts constraints on the amount of capital they can raise. By the time of a $150M exit, most biotechs will have raised about $50M to get them to a Proof of Concept trial in humans. This is not a lot of money in the development world so biotech development has to be as capital efficient as possible.

A number of venture firms are taking the virtual approach themselves as a way to contain costs. Instead of funding a company that has to hire full time staff, they are acquiring assets and using an “entrepreneur-in-residence” to run the development program. They then outsource all of the activities including scientific oversight and project management.

Another trend is the movement in the largest pharmaceutical companies to downsize their R&D groups and turn the research over to a CRO. There are two different cultures when you compare large Pharma to contract research. Large Pharma has a low risk culture that favors killing a product over taking a chance with it; this makes research very expensive. The CRO culture is focused on making money and keeping cost under control; this can make research more cost effective. I have had some experience in this area after having been the VP of Laboratory Operations for one the biggest CROs in the US. I can recall the dedication we had to keeping our costs in line and making our services competitively priced. Large Pharma does not have that concern so it becomes more cost effective for them to outsource the research. This in turn has prompted some of the large Pharma companies to establish alliances with specific contractors. This arrangement benefits both sides. The large Pharma gets very competitive pricing and the CRO gets guaranteed business.

One more trend in big pharma is to sell off their R&D group or at least downsize them in favor of finding new drugs at biotech firms. The cost of developing drugs in big pharma keeps escalating without a corresponding increase in new drug approvals. A study conducted by DiMasi and Grabowski (Manage. Decis. Econ. 28: 469–479 (2007)) concluded that mean out of pocket cost for a compound developed by big pharma from preclinical through Phase 2 was $130M. Since most biotech firms are getting about $50M to reach this point, it seems clear that biotech companies can be much more cost efficient than their big brethren.

Lowering costs can be achieved by new business models and concepts. The emergence of virtual models and the infrastructure to support them have opened the path to many new ways to getting research conducted with a minimum of expenditure.

There is a more in-depth discussion in a White Paper entitled "Virtual R&D Teams Enable Real Cost Savings" at the Resource Center/White Papers.

Why Are Amorphous Dispersions Used in Formulation Development?

Wed, 07 Mar 2012 20:55:00 GMT

An amorphous dispersion is a mixture of a drug and a polymer in which the polymer disperses the drug and helps to maintain it in an amorphous form.

The primary use of this technology is to increase the dissolution and apparent solubility of poorly soluble drugs. Another use of this system is to develop controlled release formulations. If the drug is truly dispersed on a molecular level, then its dissolution will be controlled by erosion of the polymer rather than by actual dissolution of the drug. This could then provide a pH and drug solubility independent mechanism of controlled release.

Different processes can be used to generate an amorphous dispersion. It may be possible to melt the drug and a polymer together and then use hot melt extrusion techniques to make the dosage form. It is also possible to dissolve a polymer and the drug in a common solvent and then use spray drying to evaporate the solvent.

There is a more in-depth discussion and more techniques in a White Paper at the PharmaDirections Resource Center.

Regulatory Environment in Australia

Tue, 07 Feb 2012 21:18:00 GMT

It seems that interest is growing for starting Phase 1 trials in Australia due in part to the comparative ease of regulatory submission, the scientific confidence in the results and the lower costs. There is quite a bit of regulatory history in Australia that might contribute to a combination of adherence to good clinical practices and favorable regulatory procedures.

Australia started regulating pharmaceutical products in 1969 after some patients in a Melbourne Hospital were treated with Thalidomide for actinic prurigo, prurigo nodularis, lupus erythematosus and Behçet's syndrome. The adverse effects of Thalidomide on patients prompted authorities to make regulations to monitor toxicity of such medicines. This experience contributed to the genesis of pharmaceutical regulations in Australia.

Australia set up a regulatory agency called Therapeutic Goods Administration (TGA) to check the quality and safety of the medicines that were marketed in Australia even before it harmonized its regulations with that of the International GMP. The TGA monitors the quality and safety of the therapeutic products in two ways: by issuing a license when the product passed the first testing and through laboratory tests by taking samples off the shelf to study unfavorable or harmful reactions to medications. The TGA’s framework is based on the European model and they periodically benchmark themselves against other developed nations. In the last few years the TGA and the National Health and Medical Research Council (NHMRC) jointly established a Review of the Australian Arrangements for Clinical Trials & Access to Unapproved Therapeutic Goods.

It appears that the total cost of conducting clinical trials is in Australia is lower than in the US for several reasons. One reason is that preparing a regulatory application to start a trial in Australia is akin to filing a Clinical Trial Application in Europe. This is less involved than filing an IND in the US. Generally, the same amount of non-clinical, safety and CMC efforts are the same, but writing up the application for Australia takes less effort than preparing a US IND. Another reason is that clinical trials can be performed more economically due to the exchange rate of the U.S. dollar and the Euro that favors Australia, plus the cost of medical procedures and investigator fees are lower. This may explain why some companies in the US are contemplating conducting early stage clinical trials in Australia.

Regulatory Affairs at PharmaDirections

Alan Frazier's View of VC Funds

Fri, 20 Jan 2012 21:55:00 GMT

Alan Frazier of Frazier Healthcare has quite a few opinions about the state of venture funding in today’s financial climate. He has new ways of thinking on how biotechs can be funded and how VCs can recoup their investment.

http://www.xconomy.com/seattle/2012/01/19/frazier-looks-to-build-biotechs-for-sale-lay-groundwork-for-first-post-crisis-fund/

I applaud Alan Frazier’s assertion that he decided back in 2005 that biotechs need to be tailored to be acquired by big Pharma. I heard a very similar story from Brenda Gavin at Quaker BioVentures about the same time. Brenda was of the opinion that venture firms had to give up expecting their portfolio companies to exit after 5 years. She said Quaker had set their expectations for an exit after about 9 years – just about the time needed to go from lead identification to proof of concept in the clinic.

I also applaud Fred’s comment about big Pharma wanting to buy companies with one project. We have seen quite a few venture backed firms build up staffs of 50 to 150 and then get caught in a funding crisis when new investments were needed. By the time these larger biotechs had gone through $100M or more, new investors were unwilling to add in more capital in what would become a down round. The consequence is many of them have gone out of business. It seems like capital efficient biotechs are getting more popular these days.

Formulation development combined with a unique manufacturing process resulted in a newly issued patent that provides barriers to competition for repurposed drugs

Fri, 20 Jan 2012 19:58:00 GMT

One of PharmaDirections' formulation development experts was named as a co-inventor on a recent patent entitled "Layered Pharmaceutical Formulations". See the recent press release.

The product that is the subject of the patent employees two generic drugs, buproprion and naltrexone, in the same tablet. The problems that needed to be solved were: 1) the potential that the drugs might interact in the dosage form over time, and 2) the different drugs needed to be delivered as controlled release, but with different dissolution profiles.

To solve both problems at the same time prevent any interactions, each drug was in a different layer and these were separated by another inert layer. The middle inert layer was designed to dissolve quickly. This leaves the other drug layers to float away and release their drugs at their own individual rates.

The key point is that a patent was issued that can become an additional barrier to competition. The final product that will be introduced to the market can have a very unique look that would be difficult to duplicate by generic manufacturers who would want to introduce their own products after the FDA’s mandatory data exclusivity period.

This is one of 19 issued or submitted patents where PharmaDirections helped develop intellectual property for their clients. All patents developed by PharmaDirections are royalty free.

2012 JP Morgan Themes and Thoughts

Mon, 16 Jan 2012 21:04:00 GMT

After spending a week at the JP Morgan Healthcare Conference in San Francisco last week, I reflected on the themes that emerged this year. The two primary themes are 1) early stage biotech assets and companies are getting more attention, and 2) funding of early stage programs is increasing.

We have quite a bit of history with early stage companies and it has not all been good times for biotechs. PharmaDirections was formed in 2003 with the premise that early stage programs that relied on outsourcing were under served. We created teams and infrastructure to help companies navigate through the preclinical stages to their IND with access to a variety tools and resources that were only available to large R&D organizations. Great idea, except that these companies in need were not getting very much funding. At the time, the companies with clinical stage programs were attractive takeover targets or their clinical assets were getting the attention and money as they were being pursued by big pharmaceutical companies seeking to increase their own pipelines. There was little attention or funding given to discovery of pre-IND programs.

By 2008, many of the clinical stage companies and programs were getting acquired or the biotech company decided to become vertically integrated and take their products to market themselves. This left room for early stage assets to get some attention as large pharmaceutical companies begin scaling back their R&D groups and they looked to acquisitions as a research strategy. Unfortunately, market conditions were unfavorable for the next two years so many funding sources were depressed.

It appears from the various conversations around the JP Morgan and from recent funding events that it’s going to be a much better year for early stage companies and programs. Bruce Booth wrote in his recent Blog on Venture Backed Biotechs 2011 that investors reaped more reward from private M&A than the capital put into biotech in 2011. These results are a good portent for things to come this year for biotechs.

The new enthusiasm for early stage assets can also be measured by the number of venture funds that have been raised recently where their focus is pre-IND or pre-lead programs. Three funds recently created were Access BridgeGap Ventures, Broadview Ventures and Remeditex. Existing VCs have raised innovation funds such Bay City Capital, CMEA (Velocity) and Atlas Ventures where the intent is to acquire pre-IND candidate programs. Add to this the number of big pharmaceutical firms that are partner with small biotechs and you can see a lot of momentum building for drug programs or companies that are just getting off the ground.

Overall the biotech clients we talked to at JP Morgan were upbeat about meeting their funding needs and getting more of the programs through preclinical and into human trials. It seems like this is a good time to be in a biotech startup.

Strategic planning for big biobucks: Is Enobia Pharma’s acquisition by Alexion an example?

Wed, 04 Jan 2012 21:04:00 GMT

Enobia Pharma Corp of Montréal, Canada was purchased by Alexion Pharmaceuticals Inc., of Cheshire, Conn., at the end of 2011 for $610 million up front and $470 million in sales and regulatory milestones. Was this the result of good strategic planning?

Strategic planning is a big part of every new biotech’s efforts to plot a direction and a focus for their long term operation. Even through the best laid plans often go awry, planning for the both the expected and unexpected is a good business practice. The question is whether Enobia and Alexion had strategic plans that led to the recent purchase.

Enobia started out focused on the treatment of bone disorders with their recombinant enzyme drug candidate for the replacement of a functional enzyme known as PHEX, the deficiency of which leads to X-linked hypophosphatemia -- a form of rickets. Rickets is a disorder by which the bones of children do not mineralize properly, and X-linked hypophosphatemia results in impaired bone development and growth in children. Enobia's lead product, ENB-0040 (asfotase alfa), is a human recombinant targeted alkaline phosphatase enzyme-replacement therapy for patients suffering with hypophosphatasia.

Having tested their product in preclinical trials, Enobia raised cash and hired executive staff to build out a company capable of taking the product to market. In 2005 Benoit Huet was hired as their CEO. Prior to joining Enobia he was President of Actelion Pharmaceuticals Canada, where he successfully established the Canadian division and launched the company’s first product on the market. He had been responsible for the development, registration and market introduction of a major compound in diabetes for Novartis Pharmaceuticals. In 2007 Enobia appointed Hal Landy, MD as the company's VP medical affairs & chief medical officer. In 2008 Julie Anne Smith was appointed as Enobia's vice president, chief commercial officer, and Jayant Aphale, PhD., MBA was appointed as vice president, manufacturing and process sciences.

ENB-0040 was awarded orphan designation in the US and EU in 2008 and Fast Track status in 2009. In 2010, a Phase 2 trial showed improvements in muscle strength and lessening of pain. Since then they have initiated trials in additional age groups to extend the patient pool that their drug can treat.

Enobia has raised enough capital to take them into Phase 3 and potentially to an NDA. They raised $40 million through a private placement in 2011 to support ongoing clinical work on ENB-0040, This was on top of more than $100 million raised in venture capital and $1 .2 million that came through an FDA Orphan grant.

Alexion Pharmaceuticals had a similar story with Soliris™ (eculizumab) for PNH, a rare form of hemolytic anemia. This is an acquired genetic blood disorder characterized by destruction of red blood cells by the body's immune system. Alexion was formed in 1992 and went public four years later with a focus on providing treatments for ultra-rare diseases. In 2006, they purchased a biopharmaceutical manufacturing facility that is used primarily to produce Soliris™. In 2007, they received marketing approval in the US and the EU. In 2010, they received marketing approval in Japan.

In 2011 Alexion acquired Taligen Therapeutics, Inc., a privately held development-stage biotechnology company based in Cambridge, Mass. Taligen’s R&D programs include potential drug candidates for various genetic and orphan diseases, such as paroxysmal nocturnal hemoglobinuria (PNH), age-related macular degeneration (AMD) and organ transplant. As of the end of September, 2011 Alexion’s revenues were over $500M with a course set to earn over $700M by the end of the year. They have cash and it looks like they want to spend it on augmenting their pipeline with drugs for rare diseases. Thus the purchase of Enobia seemed to be in line with their corporate focus.

It would appear that Enobia and Alexion both had strategic plans that led to Alexion acquiring Enobia for their rare disease treatment. This purchase ranks up there with the Plexxikon buyout for $935 million in 2011, the purchase of ZymoGenetics by BMS for $885M in 2011, the purchase of Facet Biotech by Abbot for $722M in 2010, the purchase of Calistoga by Gilead for $600M in 2011 and Eurand by Axcan Holdings for $583M in 2010. If all the sales and regulatory milestones are met, the investors in Enobia will receive 7½ times their investment. This seems like quite a good payoff for them. Bruce Booth makes a point in his blog that he expects more of these exits in 2011. It may be that times are getting better for biotechs that have good treatments, have good strategic plans and can execute their plans.

PathfINDAr™ is our expert system for developing Strategic Plans.

ISTA fends off Valeant take over: are they waiting for a bigger payoff?

Mon, 19 Dec 2011 20:52:00 GMT

Valeant recently made several attempts to get into confidential discussions and due diligence with ISTA. Valeant has a history of acquiring companies that have niche products on the market and the ISTA acquisition would be in line with their business strategy to minimize their development investment and focus on marketing and sales. ISTA has several products on the market already and is in a good position to launch several more in the next few years so they probably looked like a worthwhile take over target. After getting rebuffed by ISTA, Valeant tried an unusual tactic of trying to get the shareholders of ISTA to pay attention by publishing an open letter that proposed doubling their share price with a $6.50/share buyout offer.

ISTA has been a publicly traded company for more than 10 years. Their stock price has fluctuated dramatically and has generally followed market trends. They have seen declining stock prices for the last few months and there was no indication that much had changed by the time Valeant made their proposals. However, It’s interesting that on the day that Valeant published their open letter to stock holders, the price immediately doubled. It may be that traders expect an even greater buy out price by Valeant and they are trying to get in line. ISTA may be smart to hold out and let their new products flow from development into the market before considering being acquired. At least the traders seem to think there are significant upsides in their market price on the way.

Virdante sells it assets to Momenta: Why now?

Tue, 06 Dec 2011 19:31:00 GMT

The news that Momenta is acquiring Virdante’s Sialic Switch assets leaves me wondering about the timing. Virdante received $47.8M in Series A funding back in 2009 which should have been enough to let them get through Phase 1 and 2a clinical trials. Instead Virdante is opting to sell their primary program at the preclinical stage for $4.5M upfront. It seems to me that they are missing out on a potentially big inflection point in the value creation chain – proof of concept in humans. Have they run out of money or did they have too much sunk cost to attract new financing? Those are the only reasons I can come up with to explain why the investors would be willing to cash out now.

Virdante Pharmaceuticals was started in 2007 based on research conducted by Jeffrey Ravetch, M.D., Ph.D., of The Rockefeller University. He discovered “Sialic Switch” technology which could be used to improving antibodies’ anti-inflammatory properties. Sialic Switch refers to an enzymatic glycosylation process to sialylate the Fc-linked glycans that lack sialic acid. His understanding of sialyated antibodies began when it was recognized that some disorders caused by an overactive immune system could be treated by intravenous immunoglobulin (IVIG). Research showed that sialyated antibodies could be made by attaching sialic actid to antibodies lacking a sugar group. This in turn could improve their potency.

Part of Virdante’s business plan was to use their Sialic Switch technology to enhance other antibodies of Fc fusion products. Their hypothesis was adding sialic acid to the Fc component of antibodies such a sadalirumab or entenercept could enhance their anti-inflammatory capability and their effectiveness. Last year, Virdante announced that they developed a silyated version IVIG that is 10X more potent in preclinical models. At the time their CEO stated that their $47.8M series A was sufficient to take the compound to the clinic and to get POC in humans.

Momenta Pharmaceuticals, Inc. just announced that they are acquiring the Sialic Switch assets from Virdante Pharmaceuticals, Inc. They made an upfront payment of $4.5 million and may make additional milestone payments, which could add up to $51.5 million. It seems like Virdante is getting out of this business and turning over their “baby” to someone else to develop. If Virdante used up a large portion of their Series A getting to this point, the return on investment might be fairly small. In our experience, our clients are usually looking for their exit after a significant value inflection point such as after Phase 1 or Phase 2. I wonder what prompted Virdante to make this deal now instead of getting clinical data first.

Excaliard to be acquired by Pfizer

Sat, 26 Nov 2011 11:27:00 GMT

Pfizer Inc., a pharmaceutical major based in New York, agreed to acquire Excaliard Pharmaceuticals Inc., a spin off from Isis Pharmaceuticals. This is a good example of the virtual biotech model in action.

As large pharma downsizes their R&D groups, they are becoming more reliant on virtual biotech companies to fill their pipelines. I think that creativity and entrepreneurship is much more predominant in small companies and successful exits like this one demonstrates that there can be very good returns for investors in the virtual model. An examination of Excaliard's history may provide useful lessons for other biotech entrepreneurs.

Excaliard, co-founded in 2006 by J. Gordon Foulkes, chief executive officer of Excaliard, and managing director of RiverVest Venture Partners, acquired a license from Isis to develop antisense drugs by making an upfront payment of $1 million along with equity in their company. In less than 4 years, Excaliard started three proof-of-concept Phase 2 trials of its lead product EXC 001, an antisense medicine to reduce fibrosis. The virtual biotech announced positive results from its clinical trial of EXC 001 for amelioration of skin scarring and other fibrotic disorders in August 2010. Results of the Phase 2 trial indicated that treatment with the product significantly reduced scar severity in patients undergoing an elective abdominoplasty, compared to those who were treated with placebo.

In October the same year, Excaliard appointed Thomas G. Wiggans as chairman of its board of directors. Wiggans has more than 30 years of experience in successful development and commercialization of drugs in the field of dermatology. Generally, such appointments give an indication to the market that the company is preparing to commercialize its own products. This may have been a signal that the company has been unsuccessful in attracting a large pharmaceutical company to partner with or acquire it, and it was preparing to become a vertical pharmaceutical company if necessary.

On November 22nd this year, Excaliard and Pfizer announced a definitive agreement under which Pfizer would acquire Excaliard, confirming its efforts in commercializing the developmental drug EXC 001 and disproving market speculation that the company is not able to get a large pharmaceutical company to acquire it. The acquisition is expected to close by the end of the year.

The product EXC 001, an antisense oligonucleotide in Phase 2, is designed to interrupt the process of fibrosis by inhibiting expression of connective tissue growth factor (CTGF). Overexpression of this factor in damaged skin or tissue following a surgery or a traumatic injury causes skin scarring. As the Phase 2 trials of the product has revealed positive results in reducing scar severity, Pfizer plans to continue the development of EXC 001 to address unmet medical needs in patient groups that suffer from excessive skin scarring.

The interest being shown by Pfizer in acquiring virtual biotech companies as a means to fulfilling their new product pipelines may be due to the following reasons:

Dermatological treatments are more popular because of the lower costs involved in trials compared to that for oral or parenteral drugs.
Lower turnaround time for development and faster return on investment can be achieved at virtual biotech companies.

Mikael Dolsten, president of Pfizer’s Worldwide R & D, said that the acquisition is part of the company’s strategy to implement strong internal project pipeline involving innovative and differentiated drugs from biotech partners.

Senior vice president of Biotherapeutics, Worldwide R& D, Pfizer, Jose-Carlos Gutierrez-Ramos, said that the science behind Excaliard's lead compound aligned well with the company’s focus on new treatments for fibrosis and tissue remodeling. He added that EXC 001 has the potential to become a novel therapy in an area where there are only limited options as of now.

It only took five years from the inception of the company with the closing of Series A financing to lead generation to the completion of three Phase 2 trials to being acquired for late stage development by a pharmaceutical company that can now bring the product through Phase 3 and eventually to market. This is a testament to the value of a virtual organization that stays small, achieves their objectives through outsourcing, develops an important to new therapy and provides a good return to their investors.

What is PK Modeling?

Mon, 21 Nov 2011 21:21:00 GMT

Are you trying to figure out how to take advantage of Computer PK Models in drug development? Pharmacokinetics is not rocket science; it’s far more complex. So how well can they do at actually predicting drug delivery and disposition?

There are lots of skeptics and you can’t blame them for their opinions. However the computer is not the limitation. People need to feed them their information and interpret what comes out. When it comes to modeling biological processes such as absorption, distribution, metabolism and excretion, people have to understand more than the mechanics of the model. They have to understand how all these complex living processes interact.

Each of the factors affecting absorption from the GI tract have to be taken into account. These may include stomach acid secretion, food and drink intake, gastric emptying rate, timing and level of pancreatic secretions, bile secretions, mucous thickness and viscosity, intestinal motility, pH, efflux pump expression, cellular damage, drug particle size, intrinsic dissolution, and the list goes on. PK modeling software packages can address these processes and use disintegration, dissolution, and transcellular diffusion as inputs. But, is it good enough?

Take a look at our recent article “What is PK Modeling” in our Resource Center to get some in-depth answers.

Clovis Oncology IPO: Is this the beginning of the IPO market opening?

Thu, 17 Nov 2011 19:26:00 GMT

Clovis Oncology went public yesterday and raised a whopping $130M in new money. They originally priced their offering at $13-15 per share. Most analysts expected the price to get discounted as has happened to so many other biotech IPOs in the last two years. Clovis was able to close its IPO at $13/share at the low end of their original offering. Is this a case of the market opening up as the economic indicators are improving or do you have to go for over $100M to get close to your original offering or is it due to the faith the public is placing in a management team that has a record of success. What do you think?

In March, 2010, Anthera Pharmaceuticals raised $42M at $7/share. Their original offering was $13-$15.

In April, 2010 Alimera Sciences raised $72M at $11/share. Their original offering was $15-$17.

In April, 2010, Tengion raised $30M at $5/share. Their original offering was $8-$10.

In May, 2010, Trius Therapeutics raised $45M at $5/share. Their original offering was $12-$14.

In August, 2010, NuPathe raised $75M at $10/share. Their original offering was $14-$16.

In September, 2010, Zogenix raised $56M at $4/share. Their original offering was $12-$14.

In October, 2010, Pacific Biosciences raised $200M at $16/share. Their original offering was $15-$17.

In February, 2011, Pacira Pharmaceuticals raised $42M at $7/share. Their original offering was $14-$16.

In February, 2011, AcelRx Pharmaceuticals raised $40M at $5/share. Their original offering was $12-$14.

In April, 2011, Tranzyme Pharma raised $54M at $4/share. Their original offering was at $11-$13.

In April, 2011, Sagent Pharmaceuticals raised $105.8M at $16/share. Their original offering was at $14-$16.

In July, 2011, Horizon Pharma raised $45M at $9/share. Their original offering was at $10-$12.

In October, 2011, NewLink Genetics raised $43.4M at $7/share. Their original offering was $10-$12.

What is Oral Bioavailability?

Fri, 11 Nov 2011 21:40:00 GMT

The term oral bioavailability is frequently misused. It is the percentage of the total dose that reaches the bloodstream, but it does not all reach the bloodstream at once, and so one cannot simply take a blood sample, find out how much drug is in it and divide that amount by the dose. It is quite strictly defined when used correctly. There a level of ambiguity in the scientific literature that has led some people to confuse oral absorption with oral bioavailability. The best way to understand how to use this information in developing oral formulations is to understand the barriers a drug molecule must cross to get from the dosage form in the gut to the bloodstream. We have several tools including PK modeling and GastroPlus that can help us visualize and design oral formulations that can optimize bioavailability and improve potential outcomes. Take at look at the article “What is Oral Bioavailability?” in our Resource Center for a more in-depth discussion. In some special cases we may want to prevent it. A White Paper “What if you don’t want bioavailability” that explores this topic is also available in our Resource Center. We’re interested in hearing some opinions or comments from our readers.

What is biopharmaceutics really useful for?

Sat, 22 Oct 2011 15:32:00 GMT

Biopharmaceutics is defined as the study of the physical and chemical properties of drugs and their proper dosage as related to the onset, duration and intensity of drug action. The science of biopharmaceutics is essentially comparing the dissolution of a drug to its in-vivo performance and its effectiveness. Passing this evaluation based on specific criteria has been one of the keys to getting approval from the US Food and Drug Administration. But, there is much more value to this science then initially meets the eye. Read the rest at our Resource Center White Papers.

How Should Virtual Biotechs Outsource To Be Most Effective?

Fri, 21 Oct 2011 16:31:00 GMT

Every company has creative initiative and some core competencies; activities that require these attributes should remain inside. All else is fair game for outsourcing as long as outsourcing is done effectively. Although there are many guides for finding contract research organizations (CRO) and contract manufacturing organizations (CMO), there are few for understanding how to work with them effectively. Outsourcing is a skill that has to be taught and practiced to make it work for each pharmaceutical company. This is especially important for small startup companies that need the CRO resources, but are not far enough along in their funding efforts to afford mistakes.

Many senior level pharmaceutical executives and scientists are available to provide strategic planning and project management for contract research and contract manufacturing. These executives and scientists took up the mantel of consulting when they were offered severance packages or early retirement after the wave of mergers and acquisitions affected their former organizations. In most cases, they were directors of R&D departments where they guided multiple drug development programs and are now able to use their experience to direct preclinical and pharmaceutical development projects for their clients. They are also able to step into the management team of a small company to temporarily fill in gaps while the company recruits for a permanent member.

It takes time to fully train senior scientists and managers to be effective in outsourcing skills. Pharmaceutical outsourcing consultants can provide this training as well as help by working as an intermediary between the client company and the contract research organization. The training and the expert advice is necessary when dealing with CROs because of their unique characteristics and challenges.

CROs can provide good science as well as service if properly understood and managed. It is common among CROs to hire excellent scientists with good industry experience. As these scientists become more valuable to the CRO, they are given additional staff and responsibility. There comes a point, however, when they can have more than they can handle and they become ineffective for some of their customers. Generally, one top notch scientist can manage a group of 10 to 25 staff and retain their effectiveness. Past that group size, there are too many people and projects for them to give each one their individual attention.

Dealing with CROs effectively means understanding what drives their business. CROs make money only when they are providing services. The CRO scientists have to be constantly engaged in projects for their clients. When there are gaps between projects, the CRO has to support their overhead and staff costs without revenue. This puts considerable stress on the CRO managers to keep their staffs employed as much of the time as possible. It sometimes results in over-commitments to clients and sometimes failure to meet deliverables. The antidote is continual communication between the CRO and the outsourcing manager or using project managers who have this expertise and the tools.

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Creativity in Virtual Biotech Companies

Fri, 11 Nov 2011 21:41:00 GMT

Creativity has been the cornerstone of every form of industrial revolution. Inventions from the time of Gutenberg press to the transistor to the dot.com software have provided the fuel of economic expansion. This is just as true for pharmaceuticals as it has been for all other world-changing industries. It is the reason why many diseases can now be prevented and treated without resort to hospital stays or surgical procedures.

For creativity to flourish, creative scientists need time and space unencumbered by bureaucracy. Creativity in all it manifestations is necessary to continue the biotechnology and pharmaceutical growth that services the needs of an ever expanding population and now an ever increasing proportion of older citizens. Drug development is now moving so fast that it is following a model required by the computer industry. New generations of computers are being invented so fast that the last generations of computers may last less than a year before they are replaced by the next generation. In pharmaceuticals, the most recent generation of drug treatments is quickly followed up by the next generation of therapies that offer advantages in efficacy and safety. Pharmaceutical companies are forced to reinvent blockbuster drugs to keep up with the pace. This puts more pressure on scientists to keep their creative juices flowing.

But how will all these creative scientists keep up with the ever accelerating drive for new inventions as the industry moves more towards virtual drug development?. The answer lies in both team work and in division of labor. Multi-disciplinary teams are essential for the discovery of new targets, therapies and drugs. No one scientist can know all that is necessary to be effective. Scientists from medicinal chemistry, pharmacology, toxicology and pharmaceutics must join with their colleagues from genomics, proteomics, metabolomics and other –omics to effectively address the newest drug challenges. Their drug discovery process must be linked and passed along to other teams that can bring the discovery to the product development stage, then to the clinical stage, then to the submission stage and finally to the marketing stage.

In a virtual world, the tools exist so each of the core team members representing discovery, product development, clinical development, regulatory submission and marketing can focus on their specialized areas of expertise while all the time working together with their counterparts in each of the other teams. Project management tools and communication avenues using the web or cloud servers now provide the means and the forum to allow creativity to flourish for virtual biotech development.

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Fri, 27 Apr 2012 14:29:00 GMT

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