Context for the Update

At Quintessence, we are in the midst of an oncology Phase I clinical trial, which primarily involves increasing the dose of our drug from low levels to higher levels while monitoring and managing side effects. As a result, potential partners, shareholders and colleagues often ask what dose level we’re currently using to treat patients. The answer is straightforward but, particularly as the trial has progressed, not very fulfilling for me to give. The reason is that dose is just the first step in answering the question: Can you give enough drug to patients to see benefit?

There are two sets of information that take the next steps in addressing this question in a first in human trial.

• What are the pharmacokinetics (PK, often referred to as exposure) of the drug in this trial?
• Are drug levels in humans similar to the levels needed to see efficacy/benefit in model systems?

I had to pull our data, but below is a straightforward look at the significance of understanding exposure.

On Dose and Exposure

Dose is a straightforward way to refer to how much drug is given to a patient. However, the dose is not the only factor that contributes to how much drug a patient is actually exposed to.  The same dose of drug may result in different exposure levels in the same person on different days and/or in different patients. There are a variety of common examples and two are provided.

For many calcium channel blockers (used to treat high blood pressure), the addition of grapefruit juice to a patient’s diet can increase the amount of the drug in the patient’s bloodstream. Grapefruit juice can have the opposite effect for other drugs, such as the cancer drug etoposide. In this case, a cancer patient might take a dose of drug shown to have benefit but the amount of drug in their body may be too low.

Some differences between patients can be traced to their genes. Some individuals have subtle changes in their genetic codes that alter the way their body breaks down drugs. The most common of these differences is in a family of proteins called the cytochrome P450 enzymes (CYP450). The dose of certain drugs, such as the cancer drug tamoxifen, may be modified based on genetic testing to determine how a patient metabolizes (breaks down) such drugs.

For these reasons, understanding the relationship between a dose of a drug and the exposure of the patient to that drug is a key part of a successful drug development program.

Success = Mo’ Money? The spark for these thoughts was a conversation with fellow small business owners where someone asked who was the more successful of between myself and another person. The other person responded immediately that they were more successful. Internally, I thought they very well could be right. My friend has built a growing, profitable business from scratch with no external financing that now employs 100 people. These people are highly skilled employees who earn a good living with solid benefits.

Before I could say anything, someone asked why they believed they were more successful. Their answer was based solely on cash and didn’t account for business metrics, such as growth or profitability.

In drug development, achieving long term milestones, such as going public or getting acquired, generally marks financial success. The success of the drug being developed isn’t demonstrated until the drug is on the market after FDA approval, which takes many years and many millions of dollars. I’ve said at times that the drug development business model precludes traditional ideas like profitability. But seriously, most drug development companies, such as Quintessence, spend their majority of their existence as failures by traditional business metrics.

Success = FDA Approval? Another reason success is on my mind is that the company is approaching a pivotal time. We’ll finish our Phase I trial this year and will need to partner and/or fundraise. This transition has led to a question, generally from folks outside biotech, about how long it will take until we get FDA approval. That milestone is still at least years and many millions of dollars away and chances are very good that we won’t be the team that gets the drug there. My role here isn’t to take the drug to FDA approval but to generate sufficient support for the drug that another company, another shepherd, will.

Success = IPO? – Daphne Zohar (@daphnezohar) from PureTech Ventures recently tweeted about a 2008 Harvard Business school paper, Performance Persistence in Entrepreneurship.

The paper talks about the factors involved in the success of entrepreneurs. While we haven’t raised institutional money, the topic is still of interest so I wanted to read the paper. Almost immediately I got to a sticking point, which I have underlined in the excerpt below.

“In this paper, we address two basic questions: Is there performance persistence in entrepreneurship?  And, if so, why?  Our answer to the first question is yes: all else equal, a venture-capital-backed entrepreneur who succeeds in a venture (by our definition, starts a company that goes public) has a 30% chance of succeeding in his next venture. By contrast, first-time entrepreneurs have only an 18% chance of succeeding and entrepreneurs who previously failed have a 20% chance of succeeding.”

The definition stuck out because my sense has been (at least in biotech) that going public happens for a minority of companies and that for many of those an initial public offering is a way to access a wider pool of capital, not necessarily an exit for existing shareholders.

I tweeted that I was stuck on success as IPO and got some quick responses, including

• @drhamptn (Dave Hampton) “A disablingly narrow outcome measure: revenue is key”
• @rofrechette (Roger Frochette) “kinda limits the pool of potential study participants”
• @dbsable (David Sable) “agreed-way 2 narrow an outcome measure”

So how narrow of a sample are we talking about? The National Venture Capital Association (NVCA) has compiled the data on the exits of venture-backed companies and you can see that even in years with decent market conditions, merger and acquisition is a significantly more likely outcome than IPO.

**Includes all companies with at least one U.S. VC investor that trade on U.S. exchanges, regardless of domicile. 

Looking at the question of an IPO as a fundraising opportunity or an exit for shareholders, Bruce Booth from Atlas Ventures has blogged about the issue (underline added):

IPOs aren’t liquidity events in Biotech, they’re just financings and insiders typically do at least a third.  This insider participation isn’t the case some of the higher flying Tech IPOs, but venture investors still often hold their shares for a long time after the offering.  We held shares of Isilon for years after the IPO until its exit last fall via acquisition by EMC.  I don’t have the data to be quantitative on this, but the IRRs differences in the past decade would suggest time-to-liquidity can’t be much better for Tech.

After I got past the definition of success, I noticed that the study uses the term ‘entrepreneur’ to refer to the founders of the company. As I mentioned in the section above, the team that starts a company isn’t necessarily the same as the team that would take it “all the way” (a drug to FDA approval or in this case to IPO). In looking for some data on this point, I came across a small study from the Angel Resource Institute on 50 VC backed companies. At the time of IPO, a founder was CEO of only 49% of the VC-backed firms in the study (page 4).

Success = …. – Here is my working definition:

If we

• develop a cancer drug that is enticing enough to be advanced to FDA approval
• and convert that implicit value into a solid return for shareholders

then we will have succeeded for all of our stakeholders.

And that is what I’m off to work on now because I assure you it isn’t anywhere near as straightforward as it sounds.

*Addendum: A friend and mentor who has built lasting profitable businesses and provided return for shareholders gently reminded me that this post is a look at success through a very narrow lens. The reminder? A link to Bessie Stanley’s answer to the question What is Success. (A similar version is often credited to Emerson.)

He has achieved success who has lived well, laughed often, and loved much;
Who has enjoyed the trust of pure women, the respect of intelligent men and the love of little children;
Who has filled his niche and accomplished his task;
Who has never lacked appreciation of Earth’s beauty or failed to express it;
Who has left the world better than he found it, Whether an improved poppy, a perfect poem, or a rescued soul;
Who has always looked for the best in others and given them the best he had;
Whose life was an inspiration;
Whose memory a benediction.

There has been a lot of noise over the last few days as PricewaterhouseCoopers and the National Venture Capital Association released the venture capital (VC) investment numbers for 2011. Overall, the numbers are positive: $28.4 billion was invested across 3,673 deals, which is an increase of 22 percent in dollars and a 4 percent rise in deals over 2010. If you were reading this news in Wisconsin, you were much more likely to read about a decrease in VC dollars flowing to the state, from $112 in 2010 to $72M last year (here and here).

My first thought wasn’t that the sky is falling in Wisconsin – it was that the VC investment in Wisconsin in 2010 was probably an outlier. The 2010 story was stuck in my mind because I wrote a post about the need to distinguish between private equity and VC.

Two of the 2010 investments account for $87M of the $112M and involved a lot of individual and corporate partner dollars. Backing out these two investments leaves $25M of VC invested in WI in 2010. Looking back to 2009, only $23.9M of VC flowed to the state, a near all time low. Based on the graph below, the $72M in VC in 2011 is probably a victory – putting Wisconsin back to pre-2007 territory.

(The VC investment data comes from Thomson Reuters and is provided on the PWC website going back to 1995. The graphs here are all based on those spreadsheets.)

Now you might wonder (as I did), that last statement is true – is the uptick from $23.9M in 2009 to $72M in 2011 representative of the national VC investment environment?  A large caution in looking at the next graph is that there is a massive difference in scale between the primary y axis (VC investments) and secondary y axis (Wisconsin VC investments). With that out of the way, the national trend appears to generally be mirrored in the Wisconsin experience.

Since my day job is in biotechnology, I felt compelled to break out the data for that sector. (Biotechnology and medical devices are separate categories.) Again, note the difference in scales of the two y axes. Other than potentially being on an upswing after the low of 2009, I don’t think the numbers lend themselves to much further analysis.

Wisconsin doesn’t get a significant share of VC dollars and that is often the source of angst for folks wanting to build and scale businesses here. While we need to continue to pursue a variety of approaches to gain greater access to capital to grow our businesses in Wisconsin, we shouldn’t sell the state short on what appears to be a victory, although somewhat bittersweet.

Why would a biotech COO/President tweet so much at an investment bank healthcare conference?

I would argue it wasn’t to fulfill my main JPM goal: business development. A struggle with key conferences is timing your data to have fresh additions to your story to demonstrate clear progress. My target for JPM was exposure data from our ongoing Phase I oncology trial, but by early December it was clear that the data would be delayed. Pharma companies and investors set up days of back-to-back 30 minute to hour long meetings. Rather than push for these slots, most of my scheduled meetings were quick, informal contacts or more leisurely catch up meetings at the end of the day. This year I ended up with almost as many chance meetings in the halls and cocktail events, perhaps because I was open to them rather than rushing along with my head down. Overall, folks know we’re still advancing our drug and that I’ll have more of the package ready soon.

A secondary goal for me at JPM is a reality check on where our drug is in relationship to other drugs in development. Although there is a lot of talk about regional biotech hubs, our drug (and our company) are (and should be) benchmarked against the companies presenting at conferences like this one. As we approach the end of our Phase I trial, our product development plan, sometimes referred to as a target product profile, is increasingly top of mind. Seeing the clinical trial designs, plans for biomarkers (predicting responders), etc. keeps us focused on what we need to accomplish. I attended and took notes at a variety of cancer company presentations, including Exelexis, Aveo, Ariad, Agios, ImmuoGen and Seattle Genetics. As I often do when reading interesting news, I tweeted about what I was hearing – what was interesting or relevant to me.

One of the main benefits was discussing (online and IRL) the information with folks who have been in the industry longer than I have or have different perspectives. While not news themselves, some of the interesting topics I walked away thinking about are:

• Investors and partners have different pressure points.
  • For example, a public company that pushes back a deadline suffers more from the market than from potential pharmaceutical partners.
• Setting expectations is critical.
  • The CEO at Dendreon told the crowd in the breakout session that they would no longer give monthly sales because they are not predictive of quarterly results.
  • When asked about early stage drug candidates, Seattle Genetics’ CEO said they weren’t discussing them because the results of their experiments over the next year will tell them which ones will be most exciting.
• There are significant differences in covering public and private companies.
  • Forced transparency of public companies can make it easier to keep track of progress, financial and otherwise.
• Understanding the relationship of dose and efficacy is important throughout all stages of development.
  • In cancer, drugs are often given at or near their Maximum Tolerated Dose to have the greatest chance of efficacy. However, dose reductions due to side effects can make it difficult to see the drug’s benefit.
  • Exelexis is developing their cMet inhibitor cabozantinib in multiple cancer indications and have found efficacy at doses much lower than those used in some of their late phase trials.
• There are challenges to moving from one stage of drug development to another due to the need for different skill sets.
  • The transition from clinical trials to commercial (selling products) was the most prevalent area of difficulty for companies at JPM.

Why would a biotech COO/President tweet so much at an investment bank healthcare conference? Because it resulted in interesting discussions with people who are just as fascinated with cancer drug development as I am. And I learned from each one.

Drug development goes through a process that (focusing on FDA approval) looks like this:

A couple of notes on this oversimplified drug approval process graphic:

• Key milestones are often catalysts for equity investment, acquisition, etc. and as such are the topic of much discussion at JPM.
• Another key milestone is “proof of concept”, whose position can be the topic of much debate but lies somewhere between the end of Phase I and Phase III. (Perhaps POC will be a topic of a future post.)

Why do so many drug development companies gravitate to San Francisco in early January?

Biotech Companies Presenting at JPM

These companies are generally public biotechnology companies that are selected to present at JPM and therefore get good exposure to investors and analysts. You can read much more about some of the companies selected to present at JPM in this article by Adam Feuerstein at The Street. JP Morgan has a site to find additional information about the presenting companies.  Some of these biotech companies are also want to partner with pharmaceutical companies, who set up shop in hotels near the Westin St. Francis (where JPM is held)

Biotech Companies Not Presenting at JPM

In addition to the pharmaceutical companies, venture capitalists, even early stage investors, come to San Francisco for meetings in or around JPM. Biotech companies not presenting at JPM can use a single trip for introductory or follow up meetings with potential partners and funders. If companies are so inclined, there are other conferences that have grown up to showcase biotech companies at earlier stages or in somewhat different spaces. Websites have grown to allow people to find one another in San Francisco.

Any More Reasons to Come to San Francisco?

• The program at JPM also includes great keynote speakers from places like the FDA and the CMS as well as presentations by payors to calibrate the reality of who is willing to pay for these new drugs.
• There are always new people to meet or old friends to greet by the clock in the lobby of the Westin St. Francis.
• Networking doesn’t stop at the end of the day, just moves to nearby bars and restaurants for a reception or two before dinner.
• Communications people are everywhere. Seriously, PR people and journalists are in San Francisco in force to tell the stories and report the news.

For an informal glimpse into JPM, search for the #JPM12 hashtag in twitter. And if you have an interest in talking about a Phase I oncology asset, let me know.

First, Sonosite has had some relatively bold TV spots. While I was watching football this fall, I saw The Rehabilitator, which is an ad for ultrasound equipment that is supposed to provide enhanced images. How often do you see doctors with the overlay of superhero imagery (the floating cape now a white coat) in medical advertisements? 

The ad and the transaction are also notable to me because a local (Madison, WI) biotech company is in the ultrasound space. Echometrix is working to provide quantitative ultrasound imaging and to tie the imaging not only to initial diagnosis of musculoskeletal injury but also to track repair over time. Sam Adams, who runs the company, recently invited me to an open house where I had the chance to see a demo of the EchoSoft system, which uses acoustoelasticity in conjunction with ultrasound. A key differentiator to other approaches is that the technology allows for evaluation of dynamic, as opposed to static muscle. The technology came out of Ray Vanderby’s labs at UW Madison. If you are interested in seeing how it works, a beta version of their EchoSoft Portal available for research use. Since they are working on their 510(k) approval, the product is limited to investigational use. If you read about lean biotechs, Echmoetrix is a good example of doing a lot with relatively small investment. Angel investors and SBIR grants have funded the company’s product development and the team has been able to form a number of exciting partnerships that will help them collect the clinical data to support their development of the product. Their collaboration with the US Marines to evaluate possible tendon damage during training hikes was announced earlier this year. Echometrix also has a clinical trial ongoing with the PanAm clinic in Winnipeg, which is funded by Manitoba’s Science and Technology International Collaboration (STIC) fund.

One of the differences between the coasts and Wisconsin is the size of our biotech communities. While I can’t necessarily get a room packed full of cancer drug development folks, I can always find a group of passionate entrepreneurs working to bring medical innovation to patients.

Last week Luke Timmerman at Xconomy arranged for Daphne Zohar from PureTech Ventures to discuss the challenges facing life science venture capital (VC) these days. (You can see a storify version of the conversation.)

In my opinion, a key part of the discussion was about the nature of the VC firms themselves. About ten years ago when I started with Quintessence, the VC model seemed fairly established. A fund would invest, giving them board representation, but the company’s employees managed the business. One of the interesting features of PureTech is their model involves hands on work to advance the technology even prior to establishing a stand alone company.

Which leads me to another key distinction: If these investors are rolling up their sleeves to get their hands dirty, one might wonder if their compensation model is different from a traditional VC. During the chat, Daphne responded to a question about PureTech incentives by saying that they “get founders equity, preferred shares & even royalties on our inventions”. While I didn’t have the chance to follow up, this approach seems in contrast with the more traditional VC incentive structure of “2 & 20″, which provides annual management fees of 2% of committed capital and a 20% share of profit.

So if the activities and incentives are different, are firms like PureTech Ventures truly VC? Are these translational investors rather than venture capitalists? Perhaps a different name for these investors would better capture the possible evolution of risk capital rather than focusing on the downward trend of traditional VC.

(If you want to learn more about this type of firm, Daphne mentioned a few other firms in the space: Allied Minds (founded ’05), Flagship Ventures (founded ’00) and Third Rock Ventures (founded ’07).)

Whether you read the mainstream news or industry related publications, the message is the same: the pharmaceutical industry is facing massive challenges that include the patent cliff and diminishing return on investment (approved drugs relative to dollars invested in research and development). The industry and Wall Street don’t seem to be aligned on the how to address some of these issues, including the pros and cons of cutting R&D spending. The acceleration in layoffs in the pharma industry continues to take a toll on productivity, even of the survivors. All of these issues are overlaid on the process of getting a drug from discovery to the marketplace, where the chance of navigating that path successfully is about 1 in 10.

While biotech has been recognized as a key contributor, involved in bringing to market 34% of new drugs over the last ten years, pressure has been building on biotechnology companies from both ends of the financing continuum. With fewer risk capital dollars coming into the sector, biotech is experimenting with business models, particularly to a focus on tangible (e.g. saleable) assets, such as a lead drug. With a cold shoulder from the public markets, biotech is relying on pharmaceutical companies for their exit strategy.  In turn, pharma is shifting to risk sharing models, which entail licensing deals with smaller upfront payments vs. outright acquisition. Overall, the last few years have dramatically changed the environment for building value for biotech companies involved in drug development.

What about running made me think of the drug development ecosystem?

Avoid getting caught up in a crowd: For me, peace is one of the wonderful features of running so I rarely run road races. On Saturday, I was surrounded at the starting line by hundreds of people that would run the same route with the same overall goal, to finish. While some trained for time, others were there for fun, as evidenced by some of the very creative but at times unwieldy costumes!

My first road races came as a teenager, running with my father. I remember him coaching me through the first few events. He told me that there would be faster runners and slower runners and that the most important thing to remember was to run my own race. Even when you can tell the pace is wrong (too slow, too fast), being surrounded by a group of people all headed in the same direction makes it easy to lose track of your plan.

This Saturday, my pace for the first nine miles felt very comfortable and consistent. Then I started noticing that the crowd around me was changing. I was passing folks that had gone out too fast and being passed by runners that had held back. Even though I was aware of the challenge, I found myself checking my watch frequently, reminding myself to stay steady and run my own race.

Adapt to change: Of course, there are factors that should result in a change in plans. While the weather wasn’t a factor in Madison this weekend, the only other half marathon I have run was five years ago. My training was more structured because I was working towards a specific finishing time. The race was in May when the average high temperatures are in the 60s. Unfortunately, the temps that day started in the 70s and climbed quickly into the 90s. I wasn’t prepared for the heat and had to decide whether I would push for my time (and potentially fade out) or pull back and guarantee a finish. While altering your plans midstream may cause angst, evaluating possible outcomes with and without the changes can help you see  the right path. I was disappointed to miss my time but my decision to pull back felt validated as I passed runners on the side of the road being attended to by medical personnel.

At Quintessence, we started developing our technology prior to the changes in the market and have succeeded in getting a lead candidate into a Phase I clinical trial. My goal over the last few years has been to advance our innovative cancer drug to the point where sufficient risk was reduced for a pharmaceutical partner to value the drug enough to 1) support development moving forward and 2) provide our shareholders a return on their investment. As the good, bad and ugly news in the biotech sector continues to ebb and flow, the parallel I find in my running and my work is to continue to run my own race, being aware of my self and my environment but not distracted by others.

Finding New and Old Connections – A good place to find existing or make new connections is your existing contacts. Increasing the number of people you are connected to will help populate the People You May Know section on your home page with people you recognize. These activities combined with adding people as I meet them accounts for the vast majority of my network on LI but they just scratch the surface of the utility of the tool.
Along the lines of People You May Know, you can look for colleagues from current and past jobs as well as alumni from your schools. Since I have worked for the same small company for the last eleven years, I’ll speak to schools but companies work the same way. I went to a small school for undergrad so I can sort those alums by graduation year and get a manageable number (~500). For larger schools, this feature is not as user friendly (>3,500 people on LI graduated in 2000 from UWMadison). One of the ways to work around this is to find Groups that have a more narrow focus. The UW Madison Chemistry Department Alumni group has ~360 members and I am connected directly or one person away from just over half of those people. Another group of interest to me is Badgers in the Biotech & Pharmaceutical Industry. The group has ~640 members and I am connected directly or one away to all of the members. Looking through these pages for people I know but am not connected with could be a good step to strengthen my connections.
Making New Connections – Making connections and developing relationships follow the same principles online as in real life so I’ve incorporated some general comments on my tenets of networking. (Overall, I am a believer in balance – giving as much as you get. I am not always able to give back directly but I strive to pass that along to others, which generally means I am trying to help others connect.)
If you have met someone already, remind them in your invitation where you met and maybe what you discussed. The only time I send the generic LI invite is to someone I know well and see often, which is also the only time I will accept generic invites.
As in real life, the best way to meet someone is through a common connection. While this approach isn’t always necessary on LI, you are more likely to get a response if your message says that your colleague Jane Doe said I should contact you. If you take this approach, I suggest you ask your contact first. Send them a name (or list of names) and ask if you can use their name in your introduction. While this step seems like extra work, the potential benefits include getting additional contact suggestions and/or a recommendation to the new connection. You will also avoid any awkwardness from misinterpretations of the difference between we have a common contact vs. this person told me to contact you.
If you are approaching someone cold, your message should have at least two key components. First, you should demonstrate that you took the time to learn something about the person. Even something as simple as I see that you got your PhD at UW Madison Chemistry with Jane Doe and I got my degree there with John Smith. You are asking for something (the connection) and you should make it as easy to say yes as possible. The second part is to mention why you are interested in connecting. You are likely to get a better response if have a purpose beyond getting a job at their company, selling them something or mining their connections.
What if you are looking for a job? In my experience and from talking with others, leading with that objective doesn’t often have the desired impact unless the contact is a recruiter. An alternative could be to say what your general goals are (you are interested in a job in their city) and you are interested in what experience they can share on how to get there. Think about what you can learn from the person – how they got their job? what their company culture is? was their degree a good investment for the job they have? what training did they get to enable them to move from one discipline to another?
If you ask for something, make it easy for the other person to say yes, and/but. For example, if you want to talk to them, give options that range from easy (10 minutes on the phone) to hard (lunch). Yes, I am happy to meet with you, but we’ll have to do it by phone. If you want them to make a connection for you, give them an easy option (someone who has made the transition from basic science to regulatory affairs) and a more challenging one (Jane Doe, VP of Regulatory Affairs for a Fortune 500 company). Yes, I’d be happy to introduce you to someone in regulatory affairs, but you should start by talking with John Smith, a regulatory manager at a local company. If you ask and receive, you will likely make a strong impression if you follow up with a thank you and one line how what they did helped you.

Maintaining Connections – As long as people are using LI, access to your connections provides a self-updating electronic Rolodex. With people moving around so much these days, this feature alone could be enough to use LI. Historically, keeping track of colleagues as they move has been my most frequent use of LI. Another benefit is that you can export your connections in a few formats, including Outlook and Address Book (See How to below).

Putting the Social in Social Media – So far, the features may seem professional and not at all “social”. Remember that LI is primarily a professional site. Even the “social” discussions are more directed and formal than other places, such as Twitter.
Learning and Interacting – Discussions are generally segregated into groups, which seem overly plentiful in LinkedIn. For example, there are a wide variety of groups dedicated to cancer drug development. The value of the groups is greatly impacted by the person running the group. Many of the groups appear overrun by sales pitches for people, products, services, etc. That said, I recently had a valuable discussion in one of the oncology groups about statistical design of xenograft models. I included the thread at the bottom of this post. (I am also testing out Quora as an alternative for more technical conversations but so far have had minimal success.)

Updates, News, Etc. – You can use the network updates in LI in a similar fashion as Twitter or an RSS feed. A major difference is that you seem to be defaulted in to all updates for all contacts in LI, which makes the main page appear cluttered. You can change your settings to see only certain types of updates (see How to at end of post). I ignore connection updates (Jane Doe is now connected to John Smith.). If you move beyond the main page, the activity is also sorted by Category (Updates vs. Connections) or by Connection (See How to below). If you don’t want to come back to LI and are an RSS fan, LI does provide a way to feed your network updates into your favorite RSS feed. (Note the mention on public vs. private feeds.)
In LI, you can hide updates from specific connections on your main page. The method took me a while to notice, but when you hover your cursor over an update “Hide” will appear in the top right of the update. I have only hidden a handful of people but I can see this tool becoming more useful as updating becomes more common. I’ve mentioned previously that my current personal bandwidth on Twitter is about 100. While lists are helping with that, I would overload quickly (or simply give up) if my LI ~650 contacts started updating frequently.
One reason I have hidden updates from specific people in LinkedIn is they feed updates directly from Twitter. I’m not a fan of this approach. When I first started using Twitter, I linked the two accounts. I did not anticipate that many of my LI contacts are not on Twitter. These folks would see my messages, which were particularly confusing when a conversation broke out in Twitter. Unless you have an account, you can’t get over see the other parts of the Twitter conversation.
Updates in LI can be more appealing at times because 1) you can use real names rather than @handle and 2) you don’t need as many abbreviations when you aren’t limited to 140 characters. If you want to use both, there is an intermediate step to allow Twitter updates into your LI profile. When you give LI permission, you can add #in to a tweet and the information will show up in as a LI status update.

How To
1) Export your contacts: Go to your Contacts page. At the bottom right, click on Export Connections.
2) Control what activity you see: Go Settings. Select the Account tab. Select “Customize the updates you see on your home page” and you should see a list of the update types. You will also see a tab that says Hidden that will keep track of the connections you choose to hide on the home page. You can also access these settings from the main page by hovering on “More” and then “Customize”
3) See activity by Category or Connection: On the main page, you can see 

Hover over “More” to see “See additional views”, which will bring up 

 The final tab provides all of your updates.

Samples Discussion from a LinkedIn Group