Cambridge, Mass.-based Flagship Ventures recently launched the company’s largest fund to date, raising $270 million for its life sciences funds, money that will add around 20 new biotechnology companies to Flagship’s portfolio, according to officials. With the closing of the new fund, the company now has more than $900 million of early-stage capital under management.  Noubar Afeyan, Ph.D., managing partner and CEO of Flagship, answered questions from R&D Directions about the company’s latest cash infusion.

R&D Directions: How will this new fund impact or expand efforts in your early-stage portfolio?

Dr. Afeyan: We will continue to pursue and expand our investment and venture creation strategy through Flagship Venture Capital and Flagship VentureLabs. We have already started to put some of the money to work through investments in a few breakthrough companies such as:

• Breathable Foods, which is pioneering devices and formulations for the delivery of nutrients in a breathable format.
• Blend Therapeutics, which is developing combination medicines with the ability to control each agent’s therapeutic action.
• Tangent Medical, which will commercialize a novel intravenous catheter to improve patient and hospital staff safety and reduce complications.
• Essentient, a company that is going to transform global nutrition and food supply

R&D Directions: Can you highlight a few startup successes resulting from Flagship’s last fund, launched in 2007?

Dr. Afeyan: We invested in 24 companies, including Joule Unlimited (which has developed proprietary photosynthetic organisms to generate ready-to-use ethanol and diesel using only sunlight, CO2, and water as inputs); Agios (developing anti-cancer drugs that target tumor metabolism); Selecta Biosciences (pioneering an anti-smoking vaccine using its proprietary synthetic vaccine particles); and Permeon (which has a new class of protein therapeutics that can, for the first time, act inside a cell). We also invested in Accuri Cytometers, a later-stage company, which was sold to Becton-Dickinson for $205 million in 2011.

R&D Directions: How would you assess the general VC funding climate at the moment in the life sciences, particularly for early-stage venture firms?

Dr. Afeyan: Early-stage life science investing has been challenging for the last 10 years and returns for funds in the area back this up. Our strategy is different. First, the experience of our investment professionals is a mix of operating and investing in the sectors where we are active. We have been involved on the management teams of startups and participated in launching and growing these kinds of companies. We have sat at the table when it was time to take these kinds of companies public or sell them. In addition, we have also participated in some situations where there were failures and learned a tremendous amount from those situations.

Second, our VentureLabs program is unique in that we continue on the legacy of conceiving new companies. We have a team that institutionalizes entrepreneurship and offers proprietary investments to our limited partners. What we have found is that existing and new limited partners are comfortable and even enthusiastic about investing in our strategy. I don’t know what this says more broadly about investors becoming more comfortable with the early-stage life science investing but we are pleased that investors embraced our program with the level of support we received.

R&D Directions: Which areas in early-stage research seem to be generating the most buzz among investors? How important is it for VC firms such as Flagship to be able to adjust investment strategies in line with medical, technology, and regulatory trends?

Dr. Afeyan: In general, we strongly believe that life sciences and sustainability remain rife with opportunity for the foreseeable future, and solutions that have a meaningful and substantial impact in these two sectors and that are at the same time sustainable and practicable, will always represent the best opportunities.

As such, Flagship hasn’t focused too much on trying to pursue industry buzz and trends. We work very hard to match unmet global needs to an existing or achievable technological solution or invention, and explore ways to commercialize these breakthroughs. That’s the mission of Flagship VentureLabs, and what is creating the most buzz today. Sometimes opportunities do come to us and we invest, and sometimes, we have to create a venture where we don’t see any existing or imminent solutions.

By Michael O’Kelly, Senior Biostatistics Director, Center for Statistics in Drug Development, Innovation, Quintiles

To build their 1903 flyer, the Wright Brothers modeled and tested wing shapes in a wind tunnel to reduce costs. A century later, 800,000 simulation hours on the Cray Supercomputer fast-forwarded the design of Boeing’s 787 Dreamliner. Computer-based modeling and simulation reduced the number of prototype wings tested, from 77 for the earlier Boeing 767, to only 11 for the Dreamliner, the most advanced aircraft of its kind.

Computer-based modeling and simulation (M&S) has transformed industries from meteorology to finance. IBM’s Deep Thunder simulation predicts potential hurricane damage to city and business infrastructure in “personalized forecasts.” Financial models and simulations show investors tradeoffs between risks and returns and enable instant portfolio updates on sites such as morningstar.com and finance.yahoo.com.

With the cost of drug development at $1.3 billion per approval and success rates languishing near 8% no industry needs the power to test assumptions and predict outcomes more than biopharma. M&S-assisted drug development has been a dream for decades, but realization has been limited by three difficulties: the enormous complexity of biological systems; the lack of population-level data on real-world health outcomes; and uncertainty about regulatory acceptance of M&S applications in drug evaluation. New technology, data and experience are beginning to overcome these challenges.

M&S is poised to transform drug development by generating predictions that advance planning and decision making across the innovation lifecycle, from discovery to marketing to safe, effective drug use in medical practice. Here’s a glimpse of that future…

• A multiple sclerosis genetics study recently published in Nature used M&S to identify 29 new genetic variants linked to MS, providing a potential guide for drug target identification.

• During the 2008 influenza epidemic, FDA used M&S to identify and approve a safe pediatric dose of the experimental drug peramivir, which had never been studied in children. Results from later pediatric trials confirmed FDA’s simulated outcomes

• The American Diabetes Association worked with Archimedes Inc. to simulate a 30-year clinical trial in a modeled patient population to compare the effectiveness of current diabetes management approaches.

M&S is still in its infancy in the health sciences. But applications like these suggest its power to expand knowledge and improve efficiencies on two great frontiers of 21^st century medicine—leveraging deeper knowledge to understand interactions at the molecular level, and leveraging broader knowledge to understand health outcomes at the population level.

Computational power is growing at an astonishing rate, enabling models that integrate huge volumes of molecular and genetic information with large-population clinical datasets. Systems biologists are constructing models so complex that they are being built by consortiums for open use in “pre-competitive” research. One is the $6.7 million partnership between Sage Bionetworks and the National Cancer Institute to build models to predict breast, colon, liver and pancreatic cancer. Mountains of population-level health data are accruing in databases such as Kaiser Permanente’s EHR database of more than 28 million members spanning 40 years. These data give rise to the possibility of more and more accurate and reliable models of health outcomes.

The most mature clinical research application, PK/PD dose modeling, has been streamlining trials for a decade. M&S uses preclinical and Phase 1 PK/PD data to predict optimal doses for clinical testing, gain insight into potential impacts of dose on efficacy endpoints, and test assumptions about biomarker impacts on clinical outcomes. Population PK data are used to predict dose adjustments for special populations including children and elders.

At FDA, the number of new drug applications incorporating M&S has increased six-fold in 10 years. The 2009 guidance on end of Phase IIa meetings encourages M&S in dose selection and trial design, and FDA uses M&S to extend clinical findings and guide additional testing. Agency initiatives include DILI-sim, an agency-industry collaboration to build open-use models to predict species differences in liver toxicity.

At Quintiles, sponsor requests for M&S are increasing. Current projects include development of numerous population PK/PD models; simulating risks and benefits of various design choices to evaluate treatments for neurodegenerative disease; and modeling disease progression in rheumatoid arthritis to inform design of future programs. M&S is also being used to improve portfolio management by addressing greater levels of real-world uncertainty.

M&S is expanding rapidly as applications begin to break down silos and bring multiple disciplines together to apply data and test assumptions. Given predictions that full M&S realization could reduce development costs by 50%, it will soon be a “must have” tool across the development lifecycle.

Future growth for the biomedical industry faces growing and unprecedented threats, according to a newly released survey of CEOs from life sciences companies in California, the largest biomedical cluster in the world. The three biggest threats reported were access to capital, a burdensome and uncertain regulatory environment, and lack of innovation and productivity in research and development.

The survey, which targeted about 100 companies focused in the areas of pharmaceuticals, biotechnology, medical devices, diagnostics, or medical equipment, was released during a briefing at this week’s JP Morgan Healthcare Conference in San Francisco. The survey was conducted in November by the California Healthcare Institute, BayBio, and PricewaterhouseCoopers US.

In perhaps the most telling finding, nearly three quarters of biomedical industry CEOs surveyed said their companies have had to delay an R&D project in the past year. Lack of funding was the top reason for project delays cited by private company CEOs, and accounted for more than 40% of delays by all public and private companies in the survey.

“That’s the first time we’ve really seen that significant percentage of CEOs that have said that their companies are in that box,” Tracy Lefteroff, national life sciences partner, PwC, tells R&D Directions in an interview. “That’s pretty significant. And it’s the first time since I’ve been working in the industry since the mid-’80s that we’ve seen that kind of high percentage of CEOs that believe that their company is having trouble accessing capital.”

In another concerning finding, eight in 10 CEOs surveyed agreed or strongly agreed that the current FDA regulatory approval process has slowed the growth of their organization. The majority of respondents believe the regulatory environment in the United States is adversely impacting the availability of capital and the comfort level of investors to invest in experimental drug discovery and development work. Twenty-eight percent of CEOs cited regulatory issues as the primary reason an R&D project was delayed.

Alexis Lukianov, chairman and CEO of NuVasive, a medical device company focused on surgical products and procedures for the spine, was part of a panel at this week’s briefing, and said product approval delays by FDA cost NuVasive about $70 million in lost revenue in 2011 and into 2012, and forced the company to reduce its headcount growth plan by potentially 15%. Mr. Lukianov says NuVasive has released about 10 new products per year over the last six years, but that output was cut in half in 2011.

“It’s the moving goal post,” Mr. Lukianov says. “It’s the fact that we pre-agree with FDA on a route, on a protocol, and on a timeframe. We go through all of these steps, which we planned millions of dollars for and which we have an endpoint relative to revenue and jobs. We go through all of these steps only to come to this nexus, which then drives it to [FDA saying] we need more data or we need more information, without any real reason for doing so.

“What we want to see is transparency and making sure that a deal is a deal. Now if something changed relatively to safety or efficacy, we would be the first to agree that we should make adjustments; nobody’s saying we don’t care what the outcome is. But there are plenty of people getting the benefits of these therapies in other parts of the world, but we can’t get them [approved] in the United States.”

Mr. Lefteroff points out that the problems of FDA-sanctioned delays and dwindling access to capital go hand-in-hand. When companies are forced to delay projects amid additional requests by regulators, investors believe there is less reason to fund them, he says. Conversely, as these same companies get less capital, they are forced to delay promising projects internally.

“There’s no transparency on what it’s going to take to get these companies through the regulatory process and get products onto market,” Mr. Lefteroff says. “A lot of the VCs just aren’t filling the tank anymore. They’re saying they can’t afford it. When you look at what’s happened to them and their industry, you can certainly understand that. A lot of these guys are being forced out of business because the returns aren’t there. If the returns aren’t there, they can’t get products approved through the FDA.”

The survey also highlights the shifting trend of biomedical companies to tap alternative sources of funding, realizing traditional private equity and venture capital channels have become increasingly difficult to access.

Forty-four percent of biomedical CEOs surveyed said they will look to licensing agreements and corporate partnerships as a source of finance in the next 12 months, double the number of CEOs who last year reported that their companies were using this route.

In addition, corporate venture funding, which is the investment of corporate funds into external endeavors, is expected to become a much more crucial source of funding to the industry, with 30% of CEOs saying they will tap corporate venture capital as a finance source in the next year, versus only 10% who did so in the past 12 months.

To that end, biotech startups and mid-sized companies have increased efforts around securing R&D partnerships and licensing agreements with organizations in big pharma and biotech, who have the cash to advance therapeutic discoveries through the costly clinical-development process.

“Venture capital is not going to be able to fund you all he way through that milestone anymore,” That’s where pharma is increasingly stepping up and filling that void through collaborations, R&D partnerships, and the like. [Biotechs] are pursuing [those kinds of deals] but they’re not getting it done in the speed that venture funding has always been done. The timeframe to get those deals put in place is another significant factor in people’s difficulty in getting access to capital.”

Such arrangements, however, are become increasingly attractive to larger drugmakers, many of whom face patent expirations on several of their top products and are under pressure to replenish pipelines.

“For pharma, there’s a sense of urgency that they need to get new drugs into their pipeline and get them through the development phase,” Mr. Lefteroff says. “To the extent that they can get some of these earlier-stage drugs into their pipeline, they can get that stuff done much more quickly than waiting as they have been and only licensing or purchasing very late-stage compounds.”

Though still only a small contributor to the finance equation, disease foundations/non-governmental organizations are growing as a funding source for 11% of CEOs who plan to use these funds in the next 12 months, versus only 4% who did last year, according to the survey.

Although access to funding is a critical concern for biomedical companies, the tone of the survey and this week’s briefing point to the issues around FDA and regulation as the prevailing theme affecting R&D for these organizations. Stephen Cary, Ph.D., CEO and co-founder of Omniox, an early-stage biotech based in the San Francisco Bay area, said that the requirements from FDA on the number of patients needed in a study to demonstrate safety, particularly for a cardiovascular disease drug, are “mathematically and financially untenable.”

Eighty-percent of biomedical CEOs surveyed do not believe that FDA has the best regulatory approval process in the world, and three-quarters believe that within five years, another country could conceivably recreate the ecosystem that has made the United States the leading biomedical region in the world.

“Without a level of reduction in regulatory uncertainty, you can’t attract capital into the industry,” Mr. Lukianov says. “When you can’t attract capital into the industry, you can’t hire good people and put them together on teams in order for them to solve public health problems.”

Executives at the briefing did acknowledge the increase in FDA approvals of cancer medicines in 2011, but said there is great need to extend the trend to other significant areas of unmet medical need.

“One of the views that we’ve had is the FDA is not very good at understanding the indirect risk of discouraging product development in important areas,” says David Gollaher, Ph.D., president and CEO, California Healthcare Institute. “They’re pretty good at understanding the direct risk – if a molecule has adverse events in a patient population – but if their standards are so high that investors don’t invest in the first place and a whole area is undercapitalized, the public health harms that can come from that might be very great.”

The CEO survey was released to provide an early glimpse into the 2012 California Biomedical Industry Report, due out early next month.

If you have been following some of the buzz out of the JP Morgan Healthcare Conference this week, access to traditional venture capital remains difficult for biomedical companies, particularly for biotech startups. Thus, opportunities to forge licensing agreements or corporate partnerships with large biopharma companies has become increasingly vital for startups hoping to grow their drug-discovery businesses.

One company that has been aggressive in following such a formula is four-year-old cancer drugmaker Forma Therapeutics, which in just the last 14 months, has signed four major partnerships with players in big pharma, two of which occurred in the last week. Forma, a company of about 100 people based in Watertown, Mass., targets essential cancer pathways to create small-molecule drugs, and is building a pipeline of cancer therapies in areas such as tumor metabolism, protein-protein interactions, and epigenetics.

After announcing a $700 million exclusive cancer drug discovery alliance with Janssen Biotech Inc. (a J&J company) this morning, Forma’s recent spate of deals will bring in more than $175 million in received and expected revenue over the next four years and more than $2.5 billion in potential milestones, a Forma spokesperson tells us.

The Janssen alliance follows quickly on the heels of a deal potentially worth $815 million unveiled last week with Boehringer Ingelheim focused on discovering small-molecule drugs against oncology-relevant protein-protein interactions.

In June 2011, Forma struck an agreement with Genentech granting the Roche unit rights to acquire a preclinical small-molecule program against a single undisclosed cancer target. The parties entered into a research collaboration in which Genentech is responsible for all development activities and will have the option to buy the entire program from Forma at a defined future phase of development.

Forma has also forged alliances with Eisai Co. Ltd, Novartis, Cubist Pharmaceuticals Inc., and the Leukemia & Lymphoma Society, with additional deals planned for the coming year, according to the spokesperson.

In its newest pact, Forma will discover and develop drugs against a panel of tumor metabolism targets, and may receive project and milestone funding from Janssen over several years; up to $700 million if development, regulatory, and commercialization milestones are achieved for drug candidates successfully launched through the collaboration. Forma may be eligible for royalties on revenues from any resulting commercialized products.

The deal also allows Forma the opportunity to co-develop and maintain North American commercial rights to one program of Janssen’s selection. The parties can choose to expand the alliance to include additional targets, including areas beyond tumor metabolism.

“This collaboration with Janssen Biotech further strengthens our drug discovery capabilities and also allows us to look to the future with an opportunity to maintain North American rights, which is a key element of our strategy to create long-term shareholder value within Forma,” says Steven Tregay, Forma CEO.

Through emerging niches in cancer biology such as cancer metabolism – the practice of fighting tumors by starving them of essential nutrients – Forma hopes to offer some early returns to its investors.

The company is able to capture cancer biology with its fully industrialized discovery engine that elucidates and processes more than 40 new drug targets per year. Forma focuses on rapidly identifying the initial molecules that will provide a basis for its drug discovery programs. Then using capabilities in computational and medicinal chemistry, parallel synthesis, X-ray crystallography and relevant biology studies, the company transforms them into quality drug-like molecules that move into the development process.

With new legislation and regulatory polices calling for more pediatric research as part of a drug-development program, the need for increased education around pediatric clinical trials is paramount, experts in this space stress. Unlike the case under earlier regulations, companies developing a drug intended for an adult market can no longer defer the planning of the pediatric component of the program until after initial approval.

Therefore, earlier planning and negotiation with regulators on trials for children has become essential. To that end, contract research company INC Research recently launched a complimentary education Webinar series called “The Classroom – Sharing the Lessons of Sucessful Pediatric Strategies.”

The first session, held last week, focused on the regulatory climate for pediatric research in the United States and Europe. A second session is planned for Dec. 13, which Kathryn Bohannon, INC Research’s principal strategist for pediatrics, tells me will explore approaches in pediatric early-phase pharmacology trials.

“It’s a natural evolution,” Ms. Bohannon says. “First, we wanted to set to stage and the framework for, ‘Why are we here? What’s driving the increase in pediatric research?’ A big reason for this push is we don’t have appropriate dosing information for our children. Historically, it’s been we give the drug to adults at X milligrams per kilogram, so let’s give it to kids at that same dose. That’s just not appropriate. A key piece in many pediatric development plans is to conduct those pharmacology studies and understand the [pharmacokinetics] of the drug across the whole pediatric population.”

INC is planning quarterly Webinars in 2012 as part of the series. Topics will include global trial design, medical challenges, dosing and safety issues, ethics, logistics, parental permission, and pediatric assent. The CRO may continue the series into 2013 based on audience interest.

I asked Ms. Bohannon to share her thoughts on pediatric research legislation and the growing responsibility of sponsors to plan and negotiate trials for children more effectively. Below is our exchange:

R&D Directions: What key factors have driven the need for drugmakers to better educate themselves on pediatric clinical trials?

Ms. Bohannon: Legislation within in the U.S. (since 1997) and EU (since 2007) require that pharmaceutical companies must address the pediatric population during the drug-development process; and when applicable, design and conduct pediatric trials in the appropriate pediatric age groups, consider development of more pediatric friendly formulations, and disclose study results.

Both the FDA and EMA encourage incorporation of pediatric research early in the drug-development process. The EU’s Paediatric Regulation requires that pediatric research be addressed earlier, specifically following conclusion of pharmacokinetic studies in adults, and involves often lengthy negotiation of a paediatric investigation plan with the EMA.

As the pediatric population must be addressed within the drug-development process, an increasing number of pharmaceutical companies must conduct pediatric research studies. It is therefore important that companies increase their pediatric competency and understand the unique considerations associated with conducting studies in children.

R&D Directions: Have the evolving pediatric regulations generally been embraced by pharmaceutical companies?

Ms. Bohannon: The requirements within the U.S. and European regulations do place an additional burden on companies when it comes to product-development planning and costs. Developing and negotiating the appropriate pediatric program that will satisfy the FDA and EMA can prove to be challenging and time-consuming.

In order to more effectively and efficiently satisfy the regulations, sponsors must consider the pediatric population early in drug-development planning and proactively engage in discussions with the FDA and EMA.

R&D Directions: What resources do pharma companies need to manage pediatric trials, and do most sponsors have them in-house?

Ms. Bohannon: Depending upon the size of the company and number of products, many customers do not have internal resources with pediatric expertise and rely upon consultants and partners for support.

Pediatric trials require management team members similar to those for adult trials, but with pediatric experience. Pediatric trials are often smaller in scope than adult trials, but the amount of effort in planning and execution may be the same as for larger adult trials.

Given the many factors that complicate pediatric clinical trials, sponsors should commit sufficient time and resources to formulating a strategy before beginning pediatric studies. Such a strategy must incorporate the unique pediatric considerations with respect to key factors inlcuding regulatory/legislative requirements, study design, drug formulation, consent and assent, and age groups.

R&D Directions: Beyond perhaps some of the obvious differences, what are the unique subtleties developers need to consider in pediatric trial design and execution?

Ms. Bohannon: Importantly, the design of pediatric trials needs to be customized for children, and each aspect must be thoughtfully considered and adjusted as necessary based upon the pediatric participants. Even a clinical trial’s basic safety and efficacy endpoints might need to be adjusted for pediatric patients.

The design needs to be appropriate for the stated objectives and take into account the specific physiology, pharmacology, and normal daily activities for each age group. In designing a pediatric protocol, the company must consider the balance of risks and benefits to the pediatric participants, and design a study that minimizes risk and offers the potential for information that will improve the care of children and of the individual study patient whenever possible.

The pediatric study’s schedule of events and required procedures must be customized in order to minimize risk, discomfort, inconvenience, and overall impact on the pediatric patients and families.

Given the special needs and considerations associated with the vulnerable patient population, the inclusion of patients and parents/guardians in the research study process, and the critical focus on ensuring safety and well‐being of the pediatric participants, conducting a pediatric research study undeniably involves unique challenges.

R&D Directions: What does INC Research hope to accomplish through this Webinar series?

Ms. Bohannon: Pediatric data is more than just a requirement. We have a moral obligation to provide data for safe and appropriate pediatric dosing information and formulations for the products we develop.

As a CRO with a demonstrated commitment to pediatric research, we wanted to provide a forum for sharing information and indeed raising the awareness of the importance of pediatric research. Certainly we want to establish INC Research as the “go-to” resource for pediatric clinical development.

Inherent in effective patient recruitment for clinical trials is gaining sufficient trust from prospective subjects. Although this can be considered a universal predicate to study participation, there is a considerably greater need for this foundation when it comes to African-American patient populations, according to Carmen Gonzalez, manager of strategy and communications at Healthcare Communications Group, a patient recruitment company.

Ms. Gonzalez notes from the haunting memories of the 40-year Tuskegee experiment to the famous case involving Henrietta Lacks, whose cell line was obtained without her consent, history is filled with instances of shocking ethical breaches in medical research, particularly among African Americans.

This legacy, Ms. Gozalez says, has created a rift between the medical community and potential black study participants. In addition, it has also contributed to health disparities among African Americans in the United States, a population not well represented in clinical research, she says.

In the below guest column for R&D Directions Insider, Ms. Gonzalez details a three-part plan on how to build trust among African-American communities that can serve as a foundation for future patient recruitment.

Site selection: A good start, but is not enough

As with most studies, site selection plays a crucial role in supporting patient recruitment. The same holds true for clinical studies that bear a diversity requirement for African-American patient enrollment.

Generally, the largest representation of African Americans resides in the Southeastern United States (note New York Times census map at right). Although demographic concentration assists in locating sites that serve a predominant African-American populace, it is not enough to ensure successful patient recruitment.

In our company’s experience, the ideal site possesses strong community ties. Accordingly, although location is important, local networks among black neighborhoods is more significant.

Community contact

Not every site is equipped with a social system of local relationships, but there are ways to cultivate such ties. Starting at the site clinic, it is important to have African-American staff. This signals a commitment to the community that the site reflects its interests from the inside out.

Ideally, site employees will possess outreach experience in performing recruitment. In some cases, sites lack the manpower to engage in such activities. Therefore, where staffing is limited, it is crucial to tap local medical and/or nursing schools and public health graduate programs for African-American interns who may serve as an outreach team. Such students need academic field credit and with appropriate training and guidance from the site, they can extend its reach into the African-American community.

In developing strong local relationships, it is advised to pinpoint prime areas for collaboration within the African-American community that align with their social networks. For example, we have traditionally found that local black churches, barbershops, beauty shops, and nail salons to be the social “nerve center.”

Reaching out to these locales and establishing a rapport for study awareness and even off-site screenings can boost African-American study participation tremendously. Overcoming distrust of the medical community requires this proactive approach, affirming site commitment to local residents.

A prime example of using social hubs for improved healthcare is the Black Barbershop Health Outreach Network, which was founded in 2007 with the goal of addressing at-risk African-American males for cardiovascular disease and diabetes.

Health screenings were held at black barbershops, conducted by medical volunteers, in 38 cities across the United States. Participants were referred for follow-up care based on their screening findings and received preventive education on related chronic diseases. To date, over 30,000 African-American men have been screened in over 500 barbershops. The network’s latest goal is to screen 500,000 men by 2014.

As demonstrated by this program, the social web reflected by local black barbershops is a core resource where health awareness may be advanced.

Beyond the top-tier outreach locations, there is a secondary level that exists for additional study promotion. These prospects include black sorority/fraternity chapters, low-cost (or no-cost) public service announcements promoted at local radio and cable stations, and neighborhood charity, recreational, or health events within the African-American community.

The consistent message a site represents by engaging these outreach channels is that it is committed to the health of its African-American neighbors. This is the basis of trust and the beginning of healing the rift between medical practitioners and blacks.

Effective messaging

The final element in developing a long-term, trusted relationship among African Americans is to impart the right study awareness message. It is not enough to show general disease prevalence or scientific merits of clinical research. Such information is too impersonal to the casual viewer.

Messages must be relevant and specific to the African-American community. Citing health trends that affect people of color and noting the disproportionate rates of clinical trials lacking African-American participation are noteworthy facts. By tailoring study outreach messages to indicate impact on blacks, sites will find a more receptive audience and effective communication program.

Designing an effective patient recruitment program that enlists African Americans demands a commitment to engage them on their terms, building trust every step of the way. The benefits from nurturing a solid relationship go well beyond enrolling subjects into a given study; they include the promise of improved health for patients locally, better understanding of pharmacokinetics and pharmacodynamics among African Americans, and enhanced treatment models for patients everywhere.

As Martin Luther King Jr. once said, “I can walk to freedom, but only if I have a healthy body.” Bridging long-standing health disparities among African Americans begins by recruiting one patient at a time.

- Ms. Gonzalez guides Healthcare Communications Group’s pharmaceutical clients regarding patient recruitment and retention for their global research studies.

In case you missed the news, there was a pretty neat technology unveiling at this week’s annual meeting of the American Association of Pharmaceutical Scientists, which wrapped up yesterday. New partners Bio-Images Research Ltd. and Medimetrics Personalized Drug Delivery B.V. introduced a smart pill technology called the IntelliCap, declaring it a next generation clinical research tool.

Made by Medimetrics, IntelliCap is the first device that allows patient specific drug delivery by combining electronically controlled drug delivery with patient monitoring and real-time communication/interaction with the patient.

U.K.-based Bio-Images Research works largely on drug delivery systems using the non-invasive nuclear imaging technique known as gamma scintigraphy to assess formulation behavior in man. The company, under its pact with Medimetrics, will offer IntelliCap as an advanced tool for regional absorption studies in humans, supported by a full clinical trial design and management package.

The smart pill is a wirelessly controlled electronic capsule system that delivers formulations to user-defined regions of the gastrointestinal tract for regional absorption studies. This is a critical step in lead candidate screening, formulation development, and the development of drug delivery systems, according to the companies.

The IntelliCap device is made up of a microprocessor, battery, pH sensor, temperature sensor, RF wireless transceiver, fluid pump, and drug reservoir. The tool communicates via its wireless transceiver to an external control unit worn by the patient.

Use of the pill, executives say, can enable pharmaceutical researchers to tailor delivery profiles in response to pH and temperature readings returned from the capsule as often as every 10 seconds, indicating its location in the gastrointestinal tract at any given moment.

In a bigger-picture view, executives contend that the technology will reduce the time it takes to advance new drugs to the market by allowing rapid identification of promising drug candidates while quickly eliminating potential failures. Accomplishing this at present is usually only possible in later-stage development, after substantial R&D costs have been incurred, the companies note.

Morningstar’s Lauren Migliore believes that the contract research organization industry has turned a corner, citing a resurgence in new business activity and revenue growth during the past few quarters. She notes that “the second quarter marked the first period since the beginning of the drug-development slowdown that the industry saw widespread top-line growth.”

Among factors in the industry’s favor, Ms. Migliore called attention to the sector’s recent acquisition activity, which she believes could provide additional upside for CRO investors. Her expectations of an acquisition of PPD Inc. were borne out yesterday as the company entered into a definitive merger agreement under which it will be acquired by affiliates of The Carlyle Group and Hellman & Friedman in an all-cash transaction valued at $3.9 billion, after which PPD will be a private company.

Under the terms of the merger agreement, Carlyle and Hellman & Friedman will acquire the outstanding common shares of PPD for $33.25 per share in cash. PPD may solicit acquisition proposals from third parties for a period of 30 calendar days from the date of the merger agreement and may at any time respond to unsolicited proposals that the board determines are reasonably likely to result in a superior proposal. The merger agreement provides Carlyle and Hellman & Friedman a customary right to match a superior proposal. The transaction is expected to close in the fourth quarter of 2011. Following completion of the transaction, PPD will become a privately held company and its stock will no longer trade on Nasdaq.

As reported on the Wall Street Journal blog, such private-equity buyouts have declined due to the struggling economy and rocky finance markets. There were $40.4 billion worth of private-equity buyouts announced in the third quarter, the lowest quarterly dollar volume of such deals since early 2010, according to Dealogic. The value of private-equity buyouts this year has also declined 1.8 percent from 2010, according to Dealogic.

The most extensive and comprehensive genome wide associating study ever conducted was recently published in Nature. The study found clear links between human genetic markers and diseases such as cancer, diabetes, cardiovascular and kidney disorders, gout, venous thromboembolism, and Crohn’s disease.

The topic of personalized medicine via chemical biomarkers, or metabolomics, is an emerging one at the moment, and these new results could offer valuable insight for development of individualized therapies for people who may be at risk for serious disease.

In the study, researchers at the Helmholtz Zentrum Munchen Institute, King’s College, and Metabolon Inc., a biochemical profiling and diagnostic company, used metabolomic profiling on patient blood samples to identify 37 markers for genome associated diseases, with 23 of those markers describing new genetic associations with metabolic traits.

These individual biomarkers, researchers say, could be identified with a simple blood test during a routine doctor’s visit, and could determine a patient’s susceptibility to certain diseases, giving their physician a blueprint for a personalized disease treatment program.

We caught up with Mike Milburn, Ph.D., Metabolon chief scientific officer, to talk more about the study and its implications for drug development. Metabolon’s biomarker discovery platform has been used to identify markers for a number of diseases. These markers are being incorporated into clinical diagnostic tests in such areas as prostate cancer, bladder cancer, kidney cancer, nephrotoxicity of chemotherapy drugs, and diabetes/insulin resistance. The company is based in Research Triangle Park, N.C.

R&D Directions: What key insights do the new marker discoveries provide for personalized medicine efforts in diseases such as cancer, diabetes, and cardiovascular disease, among others?

Dr. Milburn: Once you understand the implications of this study, you realize that it could have very profound significance for personalized medicine. We established in this paper that each individual has his or her own metabotype that is driven by their genetics. In other words, many biochemical levels are significantly influenced by genetics, which is counter to the way a lot of people think about biochemistry.

Most people think that biochemicals go up and down with diet, environment, time of day. This study clearly demonstrates that one’s genetics is strongly penetrant to your blood biochemical levels.

The concept, however, is really not new. Archibald Garrod, who first developed the concept of inborn errors of metabolism, had also postulated that the metabolic individuality, which he termed chemical individuality, gives us predisposition or protection for disease. Only now can we measure that chemical individuality with our metabolomic’s technology and see if it is true.

We are now starting to see pharmaceutical companies interested in profiling subjects from clinical studies to see if they can be segregated into different populations that have strong drug efficacy or unwanted side effects. Our technology could very well become a routine method of discovering companion diagnostics for individualized medicine.

R&D Directions: How was this particular genome wide association study able to overcome many of the traditional limitations associated with these kinds of studies?

Dr. Milburn: Probably the best answer to this question from a technology standpoint is the quality control measures we have in place with Metabolon’s technology to ensure that samples run with the least amount of variance for all the biochemicals we measure.

Thirty-five percent of the samples we run each day are quality control samples (process blanks, process control, and technical replicates) that allow us to maintain a very tight measurement for all the biochemicals, even when we measure thousands of samples in one experiment.

We also have over a dozen QC scientists that check each experimental data set to ensure the quality of the final data set. We published the variation per biochemical in the supplemental text of this Nature paper. Maintaining this low variability obviously helped with getting such strong associations.

We also think that measuring biochemicals is closer to the primary effect of the gene and thus the associations are stronger.

R&D Directions: Can you explain the science behind metabolomics and why you think it will change the face of medicine?

Dr. Milburn: Metabolomics is profiling biochemicals, and for many reasons it’s a much more practical technology for solving many biological problems and for identifying highly relevant biomarkers. Genomics and proteomics are much more complicated in many respects than biochemicals and are farther removed from reflecting the current biological state.

The difficulty with metabolomics is that the underlying technology is not easily developed. We are many years ahead of anyone else with our technology. Many academics with mass specs or [nuclear magnetic resonance spectroscopy] are trying to do this, but they really don’t compare to the breadth of our biochemical coverage, speed, quality control, or ability to understand the biochemical data.

We also own many pioneering issued patents in the field of metabolomics for biomarker discovery that people are just now becoming aware of.

R&D Directions: What is the potential economic impact of stalling and preventing disease progression?

Dr. Milburn: Take our fasting blood test for insulin resistance that we recently published. Many of these metabolites are relatively new blood metabolites with very little literature associated with them. However, they can accurately assess how insulin resistant you are long before you have any glucose impairment.

In fact, we found that glucose itself is very far down on the list of metabolites when you really isolate insulin resistance. However, IR is the earliest predictor of potentially developing diabetes, and we believe the costs of managing diabetes is much more expensive than the costs of making someone aware that they are insulin resistant and have an opportunity to intervene earlier.

R&D Directions: Are pharmaceutical and biotechnology companies showing increased interest in incorporating metabolomics into their drug-development programs?

Dr. Milburn: We run a business to provide the technology on a fee-for service basis. We have doubled the number of studies we do in this business every year since 2005. We completed 320 client studies in 2010, processing over 30,000 samples. That is about what we have done so far in the first half of 2011.

Today, we can completely fund our company off this business and we are over 100 employees. The clinical applications of this technology, as this paper suggests, is staggering and could take the technology to a whole new level of routine applications.

We caught up with Mr. Barr after his move across country (Covance headquarters are in Princeton) to talk about his first opportunity as top executive, his plans for Synteract, and the pulse of CRO clients at the moment.

R&D Directions: What opportunities and challenges does taking this position pose?

Mr. Barr: The opportunities for the CRO market have never been better. It’s because clients are faced with unprecedented challenges with patent expires and lack of pipeline productivity. This is causing them to go back and rethink the R&D models.

Lower costs and better outcomes are mission critical. CROs will play a vital role in both areas by helping them reduce their fixed costs and getting the relevant data to the right decision makers faster.

Synteract’s target market segment is the small to mid-size pharma and biotech companies. Our combination of capabilities, customer service, and responsiveness make us a great choice for this segment. We enjoy a nice share of the California market and one of our challenges is to raise the company’s reach to areas outside of the West Coast.

R&D Directions: What are your initial plans for the company? Is the mission to expand globally?

Mr. Barr: My initial plan is to get very intimate with the clients and employees. I will be spending the next few weeks meeting with people at all levels of the company and meeting clients. I want a clear understanding of our capabilities and the client’s needs. My goal is to ensure alignment. I will also be reviewing the strategic plans for the company.

Our plan is to grow. To do this will require us to expand beyond our current three locations (Carlsbad, Calif.; Morrisville, N.C.; and Prague, Czech Republic). It will also require us to meet the increasing global footprint our clients desire. We are reviewing a number of strategic alternatives to achieve this.

R&D Directions: What are some learnings from your time at Covance, particularly in orchestrating strategic partnerships with companies like Lilly, that you can apply to your new position?

Mr. Barr: At Synteract’s heart is an undying commitment to its clients. Clients rave about our flexibility and responsiveness. It’s not a cliché. On this we will continue to build.

Obviously our size makes us more of a niche player for the large pharma companies, but for our target segment we will apply similar principles of service excellence and the desire to bring a broad array of service capabilities to meet their needs. Our size makes us a more intimate provider for our clients and that means they know everyone in the company all the way to the CEO.

R&D Directions: In light of current market trends, is there added urgency for mid-size CROs to ramp up scale – geographically and technology wise – through strategic partnerships and other models?

Mr. Barr: I believe that is correct. The whole industry is changing now. Clients want to hear your thoughts on how you can help them with their challenges. For some services this means bringing more scale and capabilities. Theory is fine, but the ability to deliver is what counts. Our goal is to have alignment around our client’s needs and our capabilities.

R&D Directions: What services, expertise, or cultural aspects at Synteract differentiates the company from other similarly positioned CROs?

Mr. Barr: The first thing you feel when you walk through the door here is that everyone is focused on our customers. The culture of service runs very deep. The genesis of this company was in data management and bio stats and the expertise runs very deep.

These services have been extended to make Synteract a full-service CRO with additional services in clinical operations, medical writing, and medical and regulatory affairs. We also have a very strong project management team.

In addition, we have a large share of the local market here in California. Our retention for clients is over 90 percent, so once they work with us they stay with us.

R&D Directions: We noticed the neat caricatures that accompany the management profiles on Synteract’s Website? Have you decided what yours will be?

Mr. Barr: I have been thinking about it. I have a number of hobbies and things of interest of which some have been taken by the staff. So I will probably select being a die-hard Pittsburgh Steelers fan.