New Bioentrepreneur article

 

We’ve just published a new article on the Bioentrepreneur site.  (Here is the HTML version. To download the PDF, use the tool on the right hand side of page.) Written by Kleanthis Xanthopoulos and Garry Menzel, both at Regulus Therapeutics, the article examines why partnerships can sometimes fail and gives advice on how to keep them operating smoothly.

A problem, the authors write, is that some biotechs

“assume that the most important part of an alliance is the money. This could not be further from the truth. A good alliance is an investment in relationships”

The article also looks at academic partnering and includes data on select technology platform partnerships over recent years. It’s a useful piece, we think, and we’re happy to share it.  Feel free to add your thoughts or criticisms in the comments section below.

 

Entrepreneurial Events

Upcoming partnering conferences and events. If we’ve missed any that might be of interest to the Trade Secrets audience, please add in the comments section below. For our previous list of events, please go here.

 


 

16th Annual Allicense

 

May 1–2, Palace Hotel, San Francisco

 

https://www.recap.com/sitehome.nsf/allicense

 

 

Ninth Annual Strategic Alliance Management Congress

 

May 7–9, Loews Philadelphia Hotel

 

https://www.healthtech.com/Strategic-Alliance-Management-Congress/

 

 

BioEquity Europe 2012

 

May 15–16, Marriott Hotel, Frankfurt

 

https://www.biocentury.com/Data/NewsCenter2/Conferences/BCConferencesIF_BioEquity.html

 

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Testing the Value Hypothesis

Medical research tool providers have driven sweeping changes to the biotech industry. By introducing technologies like DNA sequencers, thermocyclers, mass spectrometers, and others, tool providers have tremendously accelerated biological understanding, leading to advanced new treatments and diagnostics.  A prime example is the impact genomic tools are making in the emergence of personalized medicine.  Technology push is a key factor driving medical revolutions and these new tools are enabling capabilities not previously dreamed possible.

Bringing such technologies to market is the role of many biotechnology startups.  Often, these firms are penetrating markets with significant technical differentiation but limited capital resources. In a series of posts we consider the challenges faced by these companies as they bring products through the varying stages of commercialization.  A recent post discussed the use of Minimum Viable Products (MVP) in biotech.   Here we focus on the use of a MVP in the first key stage of commercialization: setting up Beta-Sites to test the Value Hypothesis.

Testing the Value Hypothesis:

The Value Hypothesis simply states that your users obtain significant value from your product when they use it.  For a breakthrough product to provide value, it must demonstrate capabilities that otherwise cannot be obtained (achieves magnitudes better sensitivity, accuracy, cost savings, usability, etc.).  Such technologies are usually developed with a specific advantage in mind, however until your instrument or tool is in the hands of a user it is unlikely you’ve considered the full benefit or burden of your value proposition.   It could be the case that your system is superior in the metric advertised, but is inferior in aspects critical to your user (throughput, speed, workflow changes, etc.).  By getting your technology into the hands of users quickly, you allow yourself the opportunity to modify your product as needed (read: pivot).  The use of beta-sites is a useful way to understand the full scope of your customer’s needs.  The following outlines some considerations that should be taken into account to ensure your beta-testing is a success.

Request Payment to Ensure Your Technology Will Be Used

Only work with those users who are as serious about your technology as you are.  Early adopters should be excited enough about your offering that they are willing to use it at its earliest stages and they are willing to pay for this early access.  Look hard for these customers and avoid those that are only interested at zero investment.  Paid beta-sites will have ownership in the success of the program and are more likely to stay with your technology through the bumps and bruises.  Importantly, if you cannot find any customers who are willing to pay for early access, you will likely have a hard time finding customers willing to ever pay at all.

Test the Core Value Proposition You’ve developed your technology with a key benefit in mind.  However, your users may prioritize your feature set differently and you should clearly identify the real and perceived value your users place on the technology.  For instance, maybe instead of the improved sensitivity of your system, it’s that it avoids tedious tasks within with the user’s work flow.  By understanding your user’s perceived value proposition, further development and marketing materials can be guided accordingly.

Identify Real and Perceived Competition & Substitution Products. Every product has competition.  It is tremendously important to understand who your user thinks that is.  Who do they initially compare your product to?  Often this is not a direct competitor but a substitute approach (for example, using label-free antibody-based detection of proteins instead of mass spectrometry).  By having a deep understanding of your user’s perspective, you will be able to anticipate challenges posed by future customers.

Determine what is required for your product to be fully integrated into your customer’s work flow.  Adopting a new technology or process is a lot to ask of your customer.  He or she is taking a significant risk by using your untested innovation and their need for pragmatism will likely match your inherent optimism.  With your user, dig deep into the requirements needed to have your equipment be in the critical path of their success.   What data package should be compiled?  What level of reliability is required?  What upstream and downstream processes need to be changed?  And so on.

Discover new potential uses of your technology.  An important bonus of providing smart people with new innovative tools is that they come up with exciting new applications of your technology.  Be acutely aware of any potential new applications introduced by the user – this could be your next big thing!

In summary, initiating beta-test sites is important tool in understanding the value proposition your product offers your customers.  With some foresight into the objectives of the program, you can extract significant learning from this process.  In a follow up post, we will discuss some of the engineering considerations that will help ensure your program is a success.

James Taylor and Joe Marotta. Find more on the Biotech Startup Blog.

The News Net

Our roundup of news stories you may have missed includes strong words from an Indian pioneer, adding a dash of biotech to Kenyan schools and a peek into the world of DIY biotech.

 

  • Kiran Mazumdar Shaw, chairman of Indian biotech giant Biocon, has called on her government to move quickly to facilitate the growth of biotech. Her wishlist for startups includes a regulatory framework and access to seed money, perhaps through a stock exchange. Read the article here.

 

  • Participants at a biosafety workshop in Kisumu, Kenya, are calling for GMO crop production and biotech foods to be part of Kenya’s education curriculum. Educators say introducing Kenyans to the technology at a later stage in life may be to blame for widespread misconceptions. More here.

 

  • Finally, the HuffPo takes a look at the burgeoning DIY biotech movement, where hackers “operating in the near-empty spectrum between academia and big biotechnology companies” are pursuing exciting science with scavenged equipment and outsourced technologies. Check it out here.



Is it the Weather?

San Francisco vs London

The economies are of similar size, the university networks can also be compared. California boasts the most successful biotech companies, but the UK has failed to produce any significant success—is it the weather?

17 degrees, sunny –San Francisco. The Californian biotechnology industry may be facing some problems, but having a track record of 25% of the USA biomedical pipeline still makes it a huge success story. Interestingly, the biotech community in the Bay area does not just form around Stanford, but also around University of California at San Francisco and around the existing biotech “superpowers”: Genentech, etc.  In short there is a community established and successful in the Bay area, there is not in London.

This means that the development of biotech in the Bay area is supported by experienced investors, management and scientists; over time experience from the likes of Amgen gets ploughed into biotechs of a second generation, and from the second into the third. This is not true across the Atlantic.

4 degrees, cloudy –London. Any successful UK start up is quickly converted into cash through a trade sale rather than developing as a company. While it is possible for each of the interest groups to blame the other – universities to bemoan the lack of finance; investors to moan about the lack of experienced management and management the lack of support, this is not helpful. I suggest we need to be joined in an effort to establish the London area as a powerhouse of biotechnology. In the London area, I include Oxford and Cambridge. We need that level of critical mass to ensure the ideas and the finance come together with a supportive environment, with facilities being key to help move ideas fast from conception to delivery into the hands of doctors for the benefit of patients.

So it is not all about the weather, baseball or cricket, shiraz or Fuller’s Best. Driving from Palo Alto to highway 101 one notices many areas where laboratory space and facilities are available to rent at rents less than 10% of the cost in the London area. The community extends to developers and facility providers, giving the scientific concepts support in the most practical way. Driving out of London on the A13 we see Canary Wharf and shopping centres and further out Dagenham, but where are those cheap and efficient developments to provide the core base?

And taking Sandhill Road from Palo Alto to the freeway I-280 one also notices HP and lawyers and many venture capital offices, built to service the ideas coming from Stanford and the biotech community from Palo Alto to downtown San Francisco. Sadly the M4 corridor out of London does not have the same concentration of venture finance.

In the Californian economy, the biotech industry provides more than 250,000 jobs. A rough figure for the UK would be 20% of that.  Each job for a skilled biotechnology worker is estimated to create almost two jobs in the less skilled parts of the local economy. In the UK, we have the skill base and the financial base to do better. So why not focus on the triangle between London, Oxford and Cambridge, and add some real determination to support companies with high growth potential to see a little more sunshine in an industry with tremendous growth prospects?

Keith Powell

 

 

Demystifying China: Understanding the Chinese IND approval process

Last year, several inquiries to us at Modular R&D, where I am a managing partner, were from companies new to China, on the subject of filing clinical trial applications. We hear comments such as “It’s taking too long,” “I cannot give out this information,” and “Why do I need to do an expensive long-tox study for a phase II?”  These are usually expressed in great frustration. So we did a workshop recently at the ChinaTrials conference, and worked with experts in regulatory affairs and preclinical studies from US, Europe and China, to look at the Chinese IND process in detail, especially how it compares to the US investigational new drug (IND) application and EU Clinical Trial Application (CTA).

In order to conduct clinical trials in China, one needs to obtain approval from the State Food and Drug Administration (SFDA). The process for doing this is called  药物临床试验申请, and is translated either as Clinical Trial Application (CTA) or Chinese IND (CIND).

The Chinese IND is functionally similar to the IND in the U.S. and the CTA in EU. The application process is like any other:  You fill out an application form, supply required materials, submit them to the relevant agency, then wait for approval, or lack of disapproval in the case of the US IND.

The required materials are similar across the regions, with minor differences.  The materials supporting clinical trial conduct are organized into four parts: Summary, CMC (Chemistry, Manufacturing, and Controls) data, pharmacology and toxicology data, and clinical trial information. Each region has its guidelines on content and format of the application materials, but the Common Technical Document (CTD) format is accepted worldwide.

Then there are the differences.

One is that the review and approval of a Chinese IND application takes a lot longer. A regular new drug application takes at least seven months, and could sometimes go to a year. This compares to the 30 day review time by the FDA and 60 day review time for the EMEA.

The reason given for the long timeline is usually the lack of personnel in the Chinese Center for Drug Evaluation (CDE), the agency under the SFDA responsible for the technical review of the application.  There are around 120 reviewers in the CDE to review over six thousand applications per year. The State Council sets employment quotas at the SFDA, so hiring more people is not as simple as a corporation adding head count. The CDE went through a reform early last year, to increase the efficiency of the approval process. However, there are parts of the timeline that are not under the control of the CDE, and the published official review time is still the same as before the reform.

Another issue is that the China IND application has high CMC requirements. This is shown in two aspects. One is that sample testing is required for several types of drugs, including imported drugs being submitted for market registration. For local drug IND, not only does the drug need to be tested, the manufacturing facilities are also inspected at the time of IND submission. The other aspect, which is more challenging for international companies, is that the China IND requires extremely detailed manufacturing protocols that many drug development companies may consider sensitive or even trade secrets.

The Chinese drug approval system was developed in the context of a large generics manufacturing industry. At the beginning the agency was faced with ensuring the production quality of thousands of small manufacturing facilities, instead of the drug safety and efficacy concerns of innovative new drugs. The regulations have been improved upon four times in the past two decades, yet one still find vestiges of this generics background. The high CMC requirements are one of these.

In a way, the long timeline issue is one of the easier to deal with, since it is predictable – you should simply plan ahead if you want to integrate China into your global development plan. In working with high CMC requirements, it’s necessary to decide the company’s comfort level in terms of sharing protocols and know-how. If what is asked for goes beyond that threshold, then China plans may need to be put on hold.

Then there are sentiments such as, “Our IND is approved and we have already started clinical trials in the States, why is SFDA still asking us to do…” which are based on generalized assumptions that the SFDA will operate like the more familiar FDA or EMEA. The Chinese regulatory system adopted many parts of US and EU system, but have adaptations and adjustments based on China’s preexisting conditions. Understanding and working with these differences is a good way to avoid frustration.

We learn to drive on the left in Britain and Japan, we learn to use inches and yards in America, and when we go to Rome, we do what Romans do. The globalization of drug development sometimes requires dexterity of mind, to understand how things come to be the way they are, and when in China, do what SFDA asks you to do.

Chloe Liu

A true reflection of the human spirit

The author, at the Great Wall of China.

On the 8th of December 2011, I was invited to represent Kuwait at the Human Variome Project (HVP) meeting, being held for the first time in Beijing, China. The meeting was a result of many months of negotiation and the finalization of a historic partnership agreement between China and the Project.

HVP is an international consortium of researchers and clinicians, and later UNESCO representatives from more than 30 countries.  It formally inaugurated in 2006 in Melbourne, Australia, with the major goal of documenting (and placing in a database) all polymorphisms and mutations in human sequences, as well as associate these with human health and diseases. This ensures that global information on genetic variation is collected, curated, interpreted and shared freely and openly.

I want to stress the words “openly” and “freely,” because for a scientist this is the best way to share data. For an entrepreneur, though, this is a waste of effort, growth, and potential income, if not secured first by patenting.

Let me explain the problem. There is no doubt that the HVP will uncover thousands of DNA changes associated with disease predisposition and outcome, and they will be useful for disease diagnosis, prognosis and theranostics.  For example, yesterday I found a base substitution in the MLH1 gene of an Arab patient with hereditary non-polyposis colorectal cancer (HNPCC). The genetic change was non-synonymous (meaning it changed the amino acid composition of the MLH1 protein from proline to serine). The DNA change may have altered the protein function, predisposing the individual to cancer. However, one really cannot tell for sure because it can be a polymorphism found in the normal population.  One of the major aims of the HVP is to stratify these DNA changes into polymorphisms or disease causing mutations.

This is achieved for HNPCC by the Insight group, one of many databases curated for the HVP.  Now that federal appeals court ruled that genes (or more accurately, DNA sequences) can be patented, overturning a lower court decision by Judge Sweet, biotechnology companies are rushing to gain from genome wide association (GWAS) and linkage studies.

On the 18th of January 2012, we learned that Myriad Genetics has acquired exclusive license to intellectual property covering the analysis of the RAD51C gene for risk of hereditary breast and ovarian cancer. The six heterozygous mutations found in the RAD51C gene by a German group confer increased susceptibility to breast and ovarian cancers (for more info, click here).

My dilemma, and the reason behind my post, is to ask how will the patenting industry cope with thousands or more disease-associated DNA sequences coming out from the HVP? Moreover, after further validation, do I submit my unique sequence I found in the MLH1 gene to the Insight database, where it may help clinicians and patients, or do I patent it first?

By the way, I know that I and my colleagues in the Middle East and beyond have hundreds of these risk-associated sequences. We do want to do something with them that reflects the true human spirit!

Fahd Al-Mulla

Entrepreneurial Events

Upcoming entrepreneurial events. Are any of these on your schedule? Of note for those in the New York area, the BIO CEO conference happens next week in midtown.  Find out more here.

 

BioPharma Asia Convention

March 19–22, Marina Bay Sands, Singapore

https://www.terrapinn.com/exhibition/biopharma-asia/index.stm

 

Bio-Europe Spring 2012

March 19–21, Amsterdam RAI Convention Center

https://www.ebdgroup.com/bes/index.php

 

24th Annual EuroMeeting of the Drug Information Association

March 26–28, Bella Center, Copenhagen

https://www.diahome.org/diahome/FlagshipMeetings/home.aspx?meetingid=25205

 

BIO IP Counsels Committee Conference

April 16–18, The Driskill, Austin, Texas

https://www.bio.org/events/conferences/ip-counsels-committee-conference-overview

 

Future Leaders in the Biotech Industry

April 20, Millennium Broadway Hotel and Conference Center, New York

https://www.biocentury.com/Data/NewsCenter2/Conferences/ConferencesFiles/FL12BrochWeb.pdf

 

The World Congress on Industrial Biotechnology and Bioprocessing

April 29–May 2, Gaylord Palms Resort and Convention Center, Orlando, Florida

https://www.bio.org/events/conferences/welcome-2012-bio-world-congress