The Big Red Biotech Blog

IBCs 8th Annual Cell Line Development and Engineering

I have several colleagues appearing at this IBC conference in San Francisco in early June.  Kevin Kayser, head of our cell engineering program, is a session chair for "Application of Genomic and Other Omics Tools, Novel Technologies and Next Generation Sequencing".  Kevin's group has just completed the development of SAFC's new CHOZN GS -/- platform cell line matched to chemically defined media and feeds.  The line has proven to offer very quick selection with resultant high titers which greatly speeds development of new clones. It has been designed to be used as a biopharmaceutical production system.  

 

IBCs 8th Annual Cell Line Development and Engineering

Another colleague, John Kolman, Senior Director, Research and Development from our new Bioreliance acquisition, will also be speaking during the session about deep sequencing methods. SAFC is also sponsoring the best poster award and will be announcing the winners of the "Cell line 2012 SAFC Young Investigator Poster Award."

Here's a quick shout-out to Kevin and John.

Posted by Bruce Lehr May 31st 2012.

Seattle Genetics Reports Groundbreaking Results With SGN-35 for Hodgkin's

Seattle Genetics will report results today at ASH Meetings of its clinical trials with SGN-35 (brentuximab vedotin) on relapsing Hodgkin's disease patients.  In the latest clinical trial, 94 percent of the patents had at least some observable tumor shrinkage - 75% saw at least 50% shrinkage and 34% went into complete remission. Side effects were mostly mild compared to conventional chemotherapy.

Seattle Genetics Report Groundbreaking Results With Drug for Hodgkin's.

The results are being hailed as groundbreaking by company officials and some clinicians involved in the clinical trials. This is the first success of a so-called empowered antibody (antibody drug conjugate) and is being closely watched in the industry. Seattle Genetics plans to file an application with the FDA by the end of March seeking approval.  About 1/3 of the 8500 patients diagnosed with Hodgkin's will relapse at some point during their treatment. Seattle Genentics is aready talking about testing the hypothesis that the drug has the potential to be the standard of care with chemotherapy for 100% of newly diagnosed Hodgkin's patients.

Seattle Genetics controls 100% of the commercial rights in the US.If approved, Seattle Genetics will have its first product on the market and will begin to transform itself from and R&D organization to a more fully integrated commercial one. By the end of 2011, the company expects to add a commercial team numbering 110 and overall staffing could grow to 475-500 employees in the next 12 months.

"We want to be the next Celgene, the next Genzyme, the next really important biotech company," said Clay Siegall, Seattle Genetics CEO.

 

Posted by Bruce Lehr December 6th 2010.

Merck Scores Coup with its CETP Inhibitor at AHA Meeting

 

According to Fierce Biotech, Merck greatly impressed an audience at the American Heart Association meetings with "jaw-dropping" data on its new CETP inhibitor, anacetrapib.  Remarkably, in a small clinical trial, the drug increased the "good cholesterol" HDL by 140% and decreased the "bad cholesterol" LDL by 40 percent.  The study's lead investigator indicated the results were wildly unexpected in both directions.

Analysts think Merck may have a mega-blockbuster on its hands with this brand new class of drug - some have predicted that anacetrapib could rack up numbers like Pfizer's Lipitor someday. Merck is anxiously trying to avoid the catastrophic failure Pfizer experienced with torcetrapib, another CETP inhibitor. Four years ago Pfizer had to halt its pivotal study after finding that the drug arm was experiencing a higher death rate.  Merck designed this initial smaller trial to look at both the therapeutic effects and at patient safety as a result.  In this trial, no significant adverse effects were noted.  Now Merck will move on to another larger trial.

In a related post in the Forbes blog, Harlan Krumholz lauds Merck for "doing the right thing" with its trial design - given Pfizer's safety disaster with torcetrapib in late stage clinicals.  Torcetrapib was anticipated to be a sure blockbuster but was found to increase deaths and heart disease events in a large clinical trial. The results surprised most observers as the drug seemed sure to be a great success.

This Merck's DEFINE study, presented to a plenary session at the meeting, confirmed the drug’s powerful effect on laboratory values. It also showed that the drug did not have a major harm or benefit – though it was too small to detect modest harms or benefits. Nevertheless, the drug has passed an important test with this trial – and Merck is now proceeding with the next step, a large clinical trial. Merck did the right thing in looking at the safety aspects too in this early stage with an appropriately designed study.  Anacetrapib will not reach the market until at least 2015, but it has passed the latest step in a way that takes patient safety in mind, as well as clinical results.

 

 

Posted by Bruce Lehr November 18th 2010.

 

CLE on Whole Genome Sequencing Coming Soon

From the Patent Doc blog, an announcement of an upcoming course examining whole genome sequencing and gene patents. The one-hour webinar is entitled "Whole-Genome Sequencing v. Gene Patents: The Coming Showdown" and will be held on Wednesday, November 3, 2010 beginning at 2:00 PM (ET). 

The  webinar will address the question:  when sequencing all or a portion of an individual's genome, are individual gene patents infringed upon by either the company providing the sequence, a company selling software to analyze the sequence, or the individual purchasing or requesting it? 

The registration fee for the webinar is $100 (government and academic rates are available upon request).  Those interested in registering for the webinar, can do so here. 

Given the Government's filing of an amicus brief in the Myriad gene case, and its announcement that it will reverse its long-standing position favoring gene patents, this CLE program would seem to be particularly pertinent.

Posted by Bruce Lehr October 30th 2010.

You Miss FDA Basic's Seminar on Generic Drugs?

The FDA Transparency blog has posted links to the agency's recent FDA Basics seminar on Generic Drugs.  This includes links to both slides and to the a 30 webcast of the seminar. There are also links to other FDA Basics seminars that have been archived.

Download FDA Generic Drugs  You can also access the slide here.  

 

 

Posted by Bruce Lehr October 7th 2010.

Wanna Learn More About Stem Cell Patent Landscape?

If you are interested in learning more about the patent environment surrounding stem cells and in particular induced pluripotent stem cells, I got the webinar for you. 

As related in the Patent Doc blog, Sunlight Research will be offering a webinar entitled "How Are iPSCs Changing the Stem Cell Patent Landscape?" on October 6, 2010 from 12:00 - 12:50 PM (EST).  Dr. Robin Chadwick of Schwegman, Lundberg & Woessner, P.A. will provide insight into the induced pluripotent stem cell (iPSC) patent activities of leading stem cell business and research institutions, illuminating potential commercialization obstacles and co-development opportunities.

The registration fee for the webinar is $147 (single viewer), $197 (2-5 viewers), or $447 (6-20 viewers).  Those interested in registering for the webinar, can do so here.

Posted by Bruce Lehr October 2nd 2010.

Biomarkers in cancer research - thoughts from AACR in Denver

via www.pharmastrategyblog.com

Sally Church, while adjusting to the high altitude of Denver at the American Association of Cancer Research (AACR) meeting on molecular diagnostics and cancer therapeutics, penned this item about new cutting edge ideas from the show.

She mentions the need for closer and more collaborative relationships between basic and clinical research in order to translate the knowledge and ideas into practice in the clinic more quickly. Essentially, better collaboration between academia, industry, between labs and between companies, even between what some may seem as competitors.  Sounds a lot like a cry for more open innovation.

A second theme she called out is the need to put more emphasis on systems biology - to look at "pathwayness" - that is trying to understand the complex pathways involved in cancer and devising strategies against the pathway versus attacking individual receptors that may only shut off portions of the pathway that can be bypassed by the cancer.

By taking the more open innovation route, and by picking up the tools we already have to more coherently apply to the pathways approach, we can potentially target more effective treatments for the individual patient -- and get there more rapidly. It again highlights a need for more work to identify biomarkers that can be used to assess successful outcomes in clinical trials within patient subpopulations - so we can apply the best treatments to the patient populations most likley to respond favorably.

Posted by Bruce Lehr September 30th 2010.

Highlights on ADCs from Interviews with The Experts

On October 27th and 28th, Boston, MA will be host city for the World ADC Summit, sponsored by Biorbis. SAFC will be in attendance as a featured Exhibitor. Several posts on this blog (1, 2, 3) detail SAFC's new facilities and capabilities to support ADC manufacturing and other high-potency APIs.

 

As a preview to the Conference, Biorbis has posted 4 interviews with industry experts on antibody drug conjugation (ADC) on its registration site.  The interviews are free to download and I'd encourage you to read them in their entirety to whet your appetite for the conference. However, I'd like to highlight some of the content here from interviews with the following experts: Dr. Jay Tibbitts at Genentech, Dr. Thomas Davis at Celldex Therapeutics, Dr. Alejandro Ricart at Pfizer, and Dr. Beverly Teicher at Genzyme.

 The appeal of ADCs is they provide the chance for a targeted therapy directed to a cancer cell rather than treat with a systemic chemotherapeutic agent for example. This is made possible by the antibody's specificity and afinity for cell surface targets. Unfortunately, not all cancers are amenable to the ADC approach.

The target protein must be expressed abundantly on the target cell surface and have very limited expression on normal cells. The target protein must also be internalized when it is bound by the antibody. That is how the toxic payload attached to the antibody is delivered within the cell. Right now, there are relatively few therapeutic target proteins that fulfill these criteria - so this approach can't be used with every cancer.

Some of the big improvements that have been made with ADCs include some of the following advances:

• Better availability of linker molecules that are stable in circulation and release their drug conjugate inside cells - deliver more drug where its needed
• Ability to make more human variants of monoclonal antibodies
• Genetically engineered antibodies with specific or selective binding sites for linker-drug attachments
• Antibody fragment technology gives molecules of smaller size, potential for better cellular penetration, and better PK characteristics
• Improved analytic testing allows monitoring your antibody, your drug conjugate, and the impact of the linker and its stability - allows measurement of antibody and free drug levels

 Areas of potential improvement of course still exist.  Some of the areas where more work is needed:

• More work is needed toward discovery of suitable tumor-associated antigens - proteomics may be used to help here
• Very important to develop diagnostic/biomarker tests alongside most ADCs to help define best patient populations for these potent drugs
• Newer, more stable linkers are still needed
• Exploration of 'bystander killing' - that is killing of other tumor cells near your target that may not express the target specific antigen. This is mediated through release of the toxin from dead tumor cells after they been killed.
• The regulatory space outside the US FDA is years behind - education with these regulators will be required as this technology moves forward

 ADCs are a relatively high COG therapeutics.  They require expertise in protein production, small molecule production and reproducible conjugate production.  In some cases, it has required collaborations between three or more companies, not counting manufacturing contractors, to bring a single ADC to clinical trial. SAFC does perform contract manufacturing of ADCs - performing the conjugations steps with specialized facilities to handle high potency drugs.

At present, the industry is watching T-DM1 and SGN-35 closely. If these ADCs in clinical investigation are successful therapeutics, other ADCs will become much more widely applied to cell surface targets that fit the necessary criteria.

Posted by Bruce Lehr Sepember 22nd 2010.

GEN Webinar: Impact High Titer Processes on Protein Quality

Over the past decade it has been all about titer, titer, titer in the biopharm industry as process development groups strove to reach "holy grail-type" production levels of 10 g/L or more (at least for MaBs). 

Now, many groups in the industry have reached that level or even exceeded 10 g/L and have concluded that may be too much. There seems to be a consensus building in the industry that 5 g/L is fine from a COGs perspective and that gains above 5 g/L don't save that much in additional COGs and create more problems with protein quality.

 

GEN will present an educational webinar on September 27th and 28th entitled, "Impact of High Titer Process on Product Quality".  Registration for the webinar is FREE.

Topics covered will include the following:

• Comparing cell-line productivity using a traditional fed-batch system versus high-density cell culture to express Fc-fusion proteins or antibodies
• Impact on aggregation, glycosylation, and in vitro activity resulting from high-density cell culture processes
• Increasing titer output without changing the genetic construct or process media
• Downsizing bioreactors while maintaining high yields of a biopharmaceutical product
• Reducing cost of goods and time to market 

The event will be moderated by GEN Editor in Chief, John Sterling.  Industry Panelists include: David Bienvenue, Assoc. Dir., VLST Corp., Wei-Kuang Chi, VP and Director, cGMP Biopharmaceutical Plant, Development Center for Biotechnology, Rolf Douwenga, VP, Global R&D, DSM Biologics

Posted by Bruce Lehr September 21st 2010.

Sigma-Aldrich to Present at UBS Conference

Sigma-Aldrich will present at the UBS Global Life Sciences Conference on Tuesday, September 21st at 12:30 PM ET in New York City. Interested parties may listen via live audio broadcast over the Internet available at http://investor.sigmaaldrich.com/.  Users can click the "Webcast" icon to access this file.

Posted by Bruce Lehr Septemeber 16th 2010.

Sigma-Aldrich Presents to 2010 Healthcare Conference

Sigma-Aldrich will be presenting at the Stifel Nicolaus 2010 Healthcare Conference on Thursday, September 16th at 2:05 PM ET in Boston, MA.  Interested parties may listen via live audio broadcast over the Internet available at http://investor.sigmaaldrich.com/ Users can click the "Webcast" icon to access this file.

Posted by Bruce Lehr September 9th 2010.

Biosimilars Near Term Require Big Bucks

The Biologics Price Competition and Innovation Act passed this year gives biologic drugs a new pathway to market - if it can be shown to be biosimilar to a marketed (reference) drug. Previously this could only be done through a complete clinical trial program.  The idea is to introduce more competition for these bio drugs similar to what has been done with Waxman-Hatch for the small molecule generic market.

A Fierce Biotech story this week explains that in order to really play in the biosimilar market in the next 5 years - a company will reqire heavy investment and infrastructure. This may seem counterintuitve as biosimilars are projected to eventually represent a cheaper (estimated at 30%) source of biologic drugs - at least that is the plan.

However, one will need to take proof of concept data with a biosimilar and ramp that up through expensive stages of clinical development - stages not suited to skills or pocket books of cash strapped small and medium biotechs.  It also means having to run fairly expensive comparison studies to marketed therapeutics.  The drugs of course will not be nmarketed prior to patent expiration on the reference product.

Experts estimate that it will take up to 8 years and $100M to $150 M dollars to get biosimilars to the point of being marketed. You also have the 12-year data exclusivity period for the reference products - a period keeps competitive drugs from being approved through a biosimilar pathway. This period starts when the reference product is first approved - and no biosimilar application filing can take place with the FDA until 4 years after approval.  By contrast, NCEs now get about 5 years of regulatory exclusivity.

Given the costs and the still substantial regulatory requirements for biosimilars, it remains likely that only a hnadful of big pharma players will be able to exploit this pathway in the next 5 years.

To learn more about this topic, the PatentDoc blog provides a link to an SMi Conference entitled, "Biosimilars & Biobetters: Aligning Business & Science for Success".  The conference is slated for London from September 22nd-23rd. Topics will cover changes in regulation and legislation in both the US and EU framework. More details on the program and pre-conference workshop can be found on the SMi site.

Posted by Bruce Lehr July 3rd 2010.

Melamine testing of Excipients Webinar June 29th

Angie Drakulich in the PharmaTech Talk blog announced that Pharmaceutical Technology will be sponsoring a webinar on June 29th that will address topic of melamine screening - particularly for pharmaceutical excipients. 

Presenters for the webinar include the FDA's Steven Wolfgang, Recall & Shortages Branch, FDA's Brian Hasselbalch, Division of Manufacturing and Product Quality, and Dave Schoneker, IPEC. 

The seminar will touch on recent movements with melamine testing and screening.  USP has been working with a coalition consisting of IPEC, PhRMA, GPhA, CHPA, and SOCMA to look a monographs for melamine testing. USP has also been exploring use of infrared spectroscopy and gel permeation chromatography in screening excipients - which should help melamine detection.

See previous Big Red Biotech Blog post for SAFC approach to melamine screening and risk assessment.

Posted by Bruce Lehr June 19th 2010.  

Concensus View from ASCO - or Not?

Many observers, see Fierce Biotech and Forbes blog as examples, have declared that Bristol-Meyers Squibb and Pfizer were the really big winners at ASCO. BMS reported sterling results with its new cancer immunotherapy drug ipilumumab for the treatment of stage 4 melanoma patients - the drug increased mean survival from 6.4 to more than 10 months which by all accounts was impressive. Some analysts are projecting this to be a greater than $1 B a year drug.

Pfizer also reported good results for its lung cancer drug, crizotinib, which stopped disease progression in 87% of patients it was tested on.  The drug is designed to be used with lung cancer patients exhibiting the ALK gene (5% lung cancer patients), as learned by Japanese researchers.  The drug could hit $800 M in annual sales. 

Other honorable mentions for the show include Roche for a very positive study with Avastin's use in the treatment of ovarian cancer.  The results suggest the drug has a future in maintenance dosing for this and possibly other cancers. 

Amgen's Prolia was also deservedly singled out.  It received FDA approval recently for the treatment of osteoporosis but is also looking for an indication in the treatment of bone loss in other cancer patients.   Should it achieve the latter approval, some analysts are projecting peak sales as much as $3 B per year.

The above describes the general consensus in the press coverage of ASCO.  However, as always, there are other with differing or more tempered views, examples include pieces from the Pharmalot blog, the Forbes blog, and yet a third offering from the Forbes blog.

The first two blogs discuss BMS' unusual study design in the ipi melanoma trial. BMS chose to compare its drug to a vaccine instead of to a placebo or other treatment standards (there aren't many).  This could make it difficult to predict how the FDA will interpret its application for approval. One big question is whether the control vaccine had any negative effects itself - thus making it a poor control.  BMS seems confident that it has vetted this possibility and is confident in its positive results. And it better be, as BMS has several other cancer immunotherapy candidates in its pipeline acquired from Medarex for $2.3 B.  Even the skeptical analysts on BMS chances of easy approval were increasing their annual peak sales estimates up to a range from $700 M - $1 B. 

The last blog post from Robert Langreth acknowledges the apparent success of the BMS and Pfizer drugs, but points out that there were a lot more failures reported than big winners.  This included failed trials involving Pfizer's Sutent (breast cancer), Roche's Avastin (colon cancer), and Lilly/BMS Erbitux (colon cancer).  Big Pharma still hasn't found a fool-proof way to select and develop cancer therapies - and Langreth questions whether there is a rush to trial before the biology is really understood. Even treating patients at earlier stages (less advanced) of cancer did not always pan out - see colon cancer.  

So in the end, it is still a mixed bag of cancer successe.  It is clear there may be some significant new therapies approved with enviable sales projections.  It is also true that there have been some dismal trial failures and a need to keep refining the way we go about developing and testing new therapies.

Posted by Bruce Lehr June 7th 2010.

CHO Genome Sequencing Underway - How Close?

At April's Cell Culture Engineering (CCE) XII Conference, Dr. Bernhard Palsson, the Galetti Professor of Bioengineering at UCSD , and founder of bio companies like Cyntellect and Genomatica, did a talk on "CHO-mics". 

CHO-mics involves full genome sequencing of CHO with comparative sequence analysis. The idea is to unravel metobolic pathways and control of processes like glycosylation.  During the talk he indicated that his collaborators have looked at 626 metabolites, 709 reactions and 104 glycosylation genes (unpublished). 

However, the most interesting statement during the talk was that Dr. Palsson's group was collaborating with the Beijing Genome Institute to sequence CHO.  They expected to publish this information after assembly and annotation.  It was implied that the work could be completed within the next two years. 

The announcement raised some eyebrows. 

   

Posted by Bruce Lehr May 15th 2010.

Brief Biopharm & Cell engineering History - ECI's CCEXII

At ECI's recent April 2010 Cell Culture Engineering Conference XII in Banf, Dr. Thomas Seewoester, Amgen presented a talk on the history (progress) of cell engineering in the biopharm industry.  He noted that the indsutry had come from talking about - how can we successfully produce a mAB to a position where  overproduction (> 10 g/L) of a mAb is conceded to result in poor product quality.  He presented the following time line and major conference themes from 1998 to 2010.

Download Biopharm History CCEXII

Dr. Seewoester indicated the industry has turned its head to some other issues besides increasing titer.  Keys for success include more focus on time to clinic, providing operational flexibility, and creating process freedom to aid manufacturing. Product quality assessment is now more of a focal point than pure productivity in g/L.

Other speakers, like Dr. Brian Kelly, Genentech, agree that when titer reaches > 10 g/L other issues such as downstream purification effiency become more important. Downstream processing is an area that needs to improve - addressing issues like reduction of yield at harvest, deamidation, aggregation, and novel equipment needs.

Cost of Goods is in pretty good shape at < $100/g for many products. There is an opportunity now to pursue smaller markets, biosimilars and personalized medicine.

As the industry becomes more mature, there is a greater financial discipline that is required.  Asset utilization becomes very important. Creating flexible processes that will accomodate product innovation is also key - "don't lock manifacturing in box."

As Dr. Seewoester concluded, "A culture of innovation is hard to build and easy to lose."

"Don't judge each day by the harvest you reap, but by the seeds that you plant."  -- R.L. Stevenson

Posted by Bruce Lehr May 15th 2010.

 

 

 

Follow On Biologics Conference

The Patent Docs blog is promoting a conference on Follow on Biologics in NYC from June 21-22. The conference will present sessions covering topics such as:

 

• impact of the 12 yr exclusivity period
• methods for demonstrating or disproving similarity
• determine safety data and technical support needed
• maximize biologic patent life
• alternative methods for approval
• overview history of US biosimilar legislation
• current FDA position on biosimilars
• lessons learned from biosimilars in international markets

This is obviously a hot area with passage of the Healthcare Reform bill.  It will likely only get hotter as biosimilars take on even greater importance with the Big Pharma pipelines drying up and their moving into the biosimilar space.  Biosimilars will of course have great impact on the growth of the World pharmaceutical market, especially in pharmerging markets.  As such, I thought it was worth passing on the information regarding this conference.

Posted by Bruce Lehr May 1st 2010.

Shout Out for Friend - Health Network Communication Conferences

As a favor to a new found web colleague, I'd like to pass along information for two upcoming conferences sponsored by Health Network Communicatons.

Exploratory Clinical Development World Europe 2010 has established itself as the largest and most influential European event for top pharmaceutical and biotechnology representatives working within exploratory development and early phase clinical trials.  For more information or to register.

The 4th annual World Drug Safety Congress Europe conference brings together top pharmaceutical, biotechnology and regulatory representatives in a forum that addresses the key issues of the industry.  For more information or to register. 

Posted by Bruce Lehr April 19th 2010. Re-posted May 1st.

 

A Message from my good buddy John - One Health Initiative looms near

My buddy, John Parfet asked me to pass along this announcement for a local event to be held near our facilities in Kansas. Since, I'm an easy touch, I agreed to comply.

One Health Initiative:Animal Health & Biomanufacturing Summit on LinkedIn Events and thought you might be interested in going! http://events.linkedin.com/One-Health-Initiative-Animal-Health/pub/228082 One Health Initiative:Animal Health & Biomanufacturing Summit Wed, Mar 03 Johnson County Community College, Overland Park, KS,

Posted by Bruce Lehr Feb 7, 2010