The Big Red Biotech Blog

Sigma-Aldrich differentiates to HPAPIs for future

The market for production of small molecule APIs is becoming much more competitive - especially as these become more genericized and manufacturing moves to lower cost (for now) Asian suppliers.

Sigma-Aldrich looks to HPAPIs as generic sector heats up.

As a result, SAFC is moving its focus away from these more generic APIs and is focusing its efforts on the product of high potency APIs (HPAPIs).  SAFC has several new facilities that are geared toward this type of higher value more difficult manufacturing -- which separates its right away from some of the lower cost, less specialized manufacturers.  This capability allows SAFC to cater to drug developers working in cancer therapeutics with both HPAPIs and antibody drug conjugates.

Sigma-Aldrich CEO Rakesh Sachdev commented on this approach at the recent JP Morgan Healthcae Conference, "A greater percentage of [custom pharma] will become highly specialized offerings."  Sigma's focus will be "on very unique products" and this is driving our expansion in the high potency area to give ourselves a competitive advantage.

Posted by Bruce Lehr Jan 18th 2012.

 

ImmunoGen and Lilly Cut ADC Deal

From Fierce Biotech, ImmunoGen and Eli Lilly announced a deal for the latter to gain an exclusive license to a defined number of treatments utilizing the formers antibody drug conjugate technology.  ImmunoGen will receive $20 M in upfront payments, can earn up to $200 M in milestones and also can earn royalties when the drugs reach commercialization.

Lilly plans to exploit the ADC technology with its pipeline of oncology drugs to "develop agents with clear clinical benefit in specific patients populations."

Posted by Bruce Lehr Dec 20th 2011.

ADCs are Hot and Offer CROs/CMOs Opportunities

As covered in the BioProcessBlog, BPTC's first bioPULSE survey found that the market was bullish on the prospects of antibody drug conjugates (ADCs) to become a major therapeutic area going forward.

Increasing interest in ADCs.

Key findings in the web-based survey included:

• 83% of respondents expect to see a signifcant increase in the number of ADCs entering the pipeline in the next 5 years
• 24% indicated that they were not currently working on ADCs but expected to be doing so soon
• 24% indicated that they were already working on ADCs
• 95% of respondents said ADCs would be as big as mAbs or very important but not quite as big as mAbs (only 5% felt it was a niche application)

Conjugation technology and linker chemistry was seen to be the biggest challenge. Survey participants cited this as an opportunity for CROs/CMOs who could provide help with conjugation and linkers and provide manufacturing.  See Big Red Biotech posts here and here.

Posted by Bruce Lehr Dec 16th 2011.

ADC Biotechnolgy Wins Grant for new ADC Production Technology

ADC Bio received a new development grant from the Welsh government for its new antibody drug conjugate manufacturing technology that it hopes will make drug production cheaper.  The new "lock and release" method will minimize production steps and cut costs.

ADC Bio wins development grant for new ADC production tech.

The new technology is performed on a solid support versus current methods done in solution at high dilution. Binding the antibody to a solid support prior to the conjugation step provides some of the following advantages according to ADC Bio:

•  column binding of the antibody followed by conjugation to the cytoxic drug allows all superfluous reactants to be washed away from the immobilized antibody
• structural integrity of the antibody binding activity is maintained
• the antibody is protected throughout the process and can't be lost by leakage providing signficant risk management for pricey material
• reportedly production yields are increased in the new process by minimizing antibody aggregation

ADC Bio expects to begin testing commercial scale production in the next year and a half.  It plans to license the technology to CMOs and drug companies. The prospect of ADC's making a much bigger splash in cancer therapeutics over the next decade bodes well for demand for ADC manufacturing services and technologies.

Posted by Bruce Lehr Dec 13th 2011.

 

T-DM1 Generates More Positive Breast Cancer Data

Roche reported more positive data on T-DM1 in its latest breast cancer trial with 137 women. In this study, T-DM1 (aka trastuzumab emtansine) showed a 41% decrease in the progression of disease versus the standard of care -- Herceptin plus Taxotere.  T-DM1 kept patients' tumors from spreading an average of 5 months longer than the standard control. T-DM1 also had only about half the reported side effects and only 25% as many patients dropped out of treatment as the standard due to adverse events. Thus T-DM1 was better tolerated by patients.

This is more good news for Roche and its partner Immunogen in their quest to gain FDA approval for T-DM1, the latest antibody drug conjugate ("empowered antibody") to seek approval.  Thus the empowered T-DM1 appears to work better than its parent Herceptin plus standard chemotherapy.  Immunogen -- responsible for linking emtansine to Herceptin -- stands to gain as well from milestones and royalties when T-DM1 is finally approved.  Phase III results still await but the trend is positive. See Fierce Biotech and Xconomy.

 

Posted by Bruce Lehr Sep 26th 2011.

Seattle Genetics and Oxford BioTherapeutics Team Up on Cancer

Seattle Genetics and Oxford BioTherapeutics (OBT) have formed a collaboration to discovery novel antibody-drug conjugates against cancer. OBT will create panels of mAbs against tumor-specific antigens identified using its Oxford Genome Anatomy Project (OGAP®) database. These will be screened using Seattle’s ADC technology.

The OGAP database is built on disease protein information generated by OBT in-house coupled with genetic and clinical data from 50 different human tissues, including 5,000 cancer membrane proteins. OBT claims the database integrates all clinical and experimental  expression data from about 1 million human protein peptide sequences, 15000  validated genes,  50 tissues/organs, 58 diseases, and about 8 million SNPs and haplotypes.

Under the deal's terms, the firms will have an equal number of alternating options to select programs from preclinical ADCs for exclusive, worldwide development and commercialization. Each firm will receive progress-dependent milestone payments and royalties on net sales of any resulting ADCs developed by its partner.

Seattle Genetics is focused on the development of antibody-based therapeutics against cancer.  Its ADC drug Adcetris was recently FDA approved for two indications:  Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL).  Seattle Genetics has three additional ADC candidates undergoing Phase I testing: SGN-75 is in development against renal cell carcinoma and non-Hodgkin lymphoma, ASG-5ME is being evaluated for the treatment of pancreatic cancer and prostate cancer, and ASG-22ME is in development against solid tumors. See GEN.

 

 

 

 

Posted by Bruce Lehr Sep 18th 2011.

FDA Clears Seattle Genetics' Adcetris for Sale in US

Cue the Trumpets!  Seattle Genetics gained FDA approval to market its antibody drug conjugate (ADC) brentuximab vedotin for the treatment of Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL).  Yeah!

This is the first ADC to gain approval on the US market and it will be sold under the name Adcetris.  The approval came about two weeks ahead of the official review date of August 30th.  This is great news for Seattle Genetics as it is the Company's first approved drug after being in business for 14 years and spending nearly $546 M in R&D to reach this point.

The industry has been watching the progress of so-called "empowered antibodies" -- antibodies linked to powerful toxins to target specific cancers -- and a big success here for Seattle Genetics will only embolden other companies in the field. Seattle Genetics also has several more candidates of its own in various stages of the clinical pipeline. 

The company didn’t discuss one of the key facts investors will want to know immediately about the new product—its price. Most analysts expect that the drug will end up costing more than $100,000 per patient, as it is given to patients in a series of intravenous infusions once every three weeks. Seattle Genetics said it plans to discuss more of its commercial plans on a conference call with investors at 8:30 am ET/5:30 am PT on Aug. 22.  See Xconomy. 

 

Posted by Bruce Lehr Aug 19th 2011.

What have you done for me lately Seattle Genetics?

Yesterday, FDA advisory panels recommended that Seattle Genetics new "empowered antibody" drug called Adcentris (brentuximab vedotin) receive accelerated approval from the agency in late August for the treatment of Hodgkin's patients (non-responsive to chemo) and patients with anaplastic large cell lymphoma (ALCL) who've relapsed.  Pretty good stuff, huh?

Today, investors thus far have rewarded the company by driving down its stock price 5.7% from $20.33 to $19.17 in premarket trading.  Wow. What have you done for me lately? See Forbes.

 

Posted by Bruce Lehr July 15th 2011.

And Then There Were Two - Adcetris Gets OK for ALCL

Seattle Genetics' Adcetris (brentuximab vedotin) recieved its second thumbs up from a second FDA advisory panel today -- this time for the treatment of anaplastic large cell lymphoma (ALCL).  Once again, the panel voted 10-0 to recommend the drug's approval. 

About 2,000 new cases of anaplastic large cell lymphoma are diagnosed each year, half get effectively treated with chemo, but once it recurs, patients are only expected to live a little more than three months. The data for the Seattle Genetics drug in this group of patients was striking. The drug completely or partially shrank tumors in 86 percent of the patients studied in a mid-stage trial (50 of 58). Most of the patients (57 percent) went into complete remissions.

The FDA has a deadline of August 30 to complete its review of the Seattle Genetics application to start marketing the drug for patients with Hodgkin’s and anaplastic large cell lymphoma. If approved, the new drug will be Seattle Genetics’ first marketed product after 14 years in business, and it would the first commercially successful version of an “empowered antibody” -- a completely new type of molecule in the fight against cancer. See Xconomy.

 

Posted by Bruce Lehr July 14th 2011.

 

 

Seattle Genetics' Adcetris Gains FDA Panel Endorsement

Seattle Genetics, as expected, got the endorsement of an FDA advisory panel to approve Adcetris (brentuximab vedotin) for the treatment of Hodgkin's lymphoma.  If the drug is now approved by the FDA for sale (decision Aug 30th), it will be the first approved antibody drug conjugate (ADC) on the market.  Another FDA expert panel will be discussing this afternoon whether or not Adcetris should also be recommended for the treatment of anaplastic large cell lymphoma (ALCL). 

"Brentuximab works and it works well. People with Hodgkin's lymphoma will have another option for treating a terrible disease," said Michael Sekeres, an oncologist at the Cleveland Clinic. See Xconomy. 

Seattle Genetics will not only be gaining its first approved drug but as an ADC the first one of that class.  This is the second drug this year from the Seattle biotech pool, besides Dendreon's Provenge, that represents a novel treatment type for a cancer.  Fierce Biotech notes in an article today that Dendreon and Seattle Genetics would both appear to be high on Big Pharma's short list of acquisitions.  Cancer therapies are expected to grow twice as fast as the rest of the pharmaceutical market (according to IMS Health) and many novel oncology drugs have been approved so far in 2011 (see next post on Yervoy).  Indeed, look for more acquisitions in the oncology space to happen.

 

Posted by Bruce Lehr July 14th 2011.

 

 

Seattle Genetics 'Empowered Antibody' on Track

Seattle Genetics antibody drug conjugate, brentuximab vedotin or Adcetris, remains on track for its hearing at FDA on Thursday.  A briefing from the FDA staff report on the drug revealed no big surprises or negatives.  Adcetris is applying for approval to treat patients with Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL). 

The FDA did note that both Seattle Genetics trials were single arm rather than double blind.  We'll need to see if that sways FDA opinion as to whether to recommend accelerated approval or not.  All signs up till now would point toward the drug receiving the go ahead. If approved, the will be Seattle Genetics first ever drug and will also be the first ADC approved. See Xconomy.

 

Posted by Bruce Lehr July 12th 2011.

 

Innovation as the Antidote to Biosimilar Market Erosion?

Here is an interesting report created by RBC Capital Markets, entitled Biosimilars - A Wall Street Perspective that discusses the evolution of biosimilars and offers an opinion as to how the market will evolve.  One of the more interesting aspects is a discussion of modifications that can be made to innovator biologics to fend off challenges from biosimilars - including such technologies:

• Pegylation - reduce injections
• Ultra potent antibodies and ligand traps - less injections, subQ dosing, safety
• Bispecific antibodies and antibody fragments - potency, dual activity
• Antibody/drug conjugates (ADCs) - potency
• Glycoengineering - potency
• Fc engineering - potency, half-life modifications, novel functions

I post frequently here about some of the ADCs advancing through the clinic - the two most advanced being brentuximab vedotin (Seattle Genetics) and T-DM1 (Genetech/Immunogen).  Both drugs are in late stages phase III and are expecting approval.  There are at least another 34 programs identified publicly -- 22 of which are in phase I or II. We can expect to see a continuing cavalcade when the first two are approved and shown to be successful.

Here's a copy of the report: Download Wall Street report on biosimilars

Posted by Bruce Lehr June 29th 2011.  

 

Cha-Ching! Seattle Genetics Gets $5M Milestone from Takeda for ADC

Seattle Genetics has begun to cash in on its antibody drug conjugate (ADC), brentuximab vedotin, for reaching a key milestone by filing an MAA with the European Medicines Agency (EMA).  The milestone triggers a $5 M payment from its licensing partner The Takeda Oncology Company.

Seattle Genetics retains marketing rights to brentuximab vedotin in the US and Canada while Takeda has the rights in the rest of the world. The partners are splitting development costs 50:50. The drug will be targeted to the treatment of Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL). Seattle Genetics application with the US FDA is pending for both applications as well.

The review date with the FDA is scheduled on Bastille Day (July 14th) and the action date is August 30, 2011. See PBR story.

 

Posted by Bruce Lehr June 28th 2011.

FDA Sets Review Date on SGN-35 ADC

Seattle Genetics has its review date with the FDA set for July 14th to get an Advisory Committee decision on its antibody drug conjugate (ADC) brentuximab vedotin (SGN-35).  BLA's for the drug's use in the treatment of Hodgkin's and anaplastic large cell lymphoma will both be reviewed in back to back sessions.

SGN-35 remains on pace to be the first ADC approved.  And if the committe recommendation is positive as widely expected, Seattle Genetics will be really have something to celebrate (besides Bastille Day) as it moves to storm the market.

 

Posted by Bruce Lehr June 16th 2011.

Seattle Genetics and Agensys Expand ADC Deal

Seattle Genetics and Agensys (now owned by Astellas) will work on their second ADC together under the terms of their existing 2007 agreement.  The new project will develop ASG-22ME directed to the Neclin-4 antigen found on bladder, breast, lung and pancreatic tumors.

With this deal, Seattle Genetics says it now has 15 ADC projects underway between its own pipeline and through external collaborations.  Agensys says the deal confirms its commitment to ADCs and building its cancer portfolio.  Seattle Genetics expects its first ADC, brentuximab vedotin (SGN-35), to be approved sometime this year by the FDA.  See PBR.

Posted by Bruce Lehr June 9th 2011.

Good Primer: Antibody Drug Conjugates (ADCs) and Cancer

This is a good post from the Pharma Strategy blog explaining what antibody drug conjugates (ADC) are and how they work in treating cancers.  ADC's are a hot area in the treatment of cancer and presumably even more so in the future.

Antibody Drug Conjugates (ADCs) in cancer research: what are they?.

Seattle Genetics' brentuximab vedotin (SGN-35), now known as Adcetris, is furthest along toward approval having been granted priority review by August 30th.  It is being considered for treatment of Hodgkin's Lymphoma and anaplastic large cell lymphoma.

The next two in line are Roche's T-DM1 for the treatment of Her2+ breast cancers and Seattle Genetics' SGN-75 for the treatment of renal cell carcinomas and non-Hodgkin's lymphoma.  Roche has a fairly large pipeline of 6-7 addtional candidates following along. Bone up with this primer and look for more new approvals in this area over the next few years.

 
Posted by Bruce Lehr May 25th 2011.

SeaGen Gets Expedited FDA Review

Seattle Genetics announced today that the FDA had accepted its BLA on its antibody drug conjugate (ADC),  SGN-35 or brentuximab vedotin, for the treatment of Hodgkin's disease and anaplastic large cell lymphoma. This is good news for Seattle Genetics and the patients with these two diseases.

SeaGen FDA Deadline Set for Aug. 30.

SGN-35 will now receive a review date from the agency by August 30th.  This new type of therapy for cancer is expected to pass muster at that time and would be the first ADC approved.

 

Posted by Bruce Lehr May 2nd 2011.

 

Seattle Genetics Stays Hot with Abbott ADC Deal This Time

Seattle Genetics that announced an extension of its deal with Takeda Millenium for its antibody drug conjugate technology earlier this month, now has another ADC deal with Abbott that focuses on a single cancer target.  The Abbott deal calls for $8 M upfront and could pay another $200 M in milestones.

This continues Seattle Genetics roll in signing licensing deals for its ADC technology in cancer therapeutics.  SeaGen now has 11 deals in place and have received licensing payments amounting to $158 M dollars.  ADC technology is widely expected to play a more and more important role in cancer treatment even though the first treatment has not made it all the way to commercialization yet.  SeaGen's SGN-35 for hodgkin's lymphoma is expected to be the first later this year. See Fierce Biotech.

 

Posted by Bruce Lehr March 25th 2011.

Takeda Extends ADC Deal with Seattle Genetics

Takeda's Millenium group has decided to go for another target in partnership with Seattle Genetics utilizing the latters ADC technology.  Millenium currently partners with SeaGen on SGN-35 or brentuximab vedotin for the treatment of Hodgkin's lymphoma. 

SGN-35 is an antibody drug conjugate or so-called "empowered antibody".  The antibody specifically targets the intended cancer cell with a coupled toxic compound to be delivered to kill that cell. SeaGen's SGN-35 and Genetech's T-DM1 both seek to be the first licensed ADC's and there is a lot of excitement for these technologies.

SeaGen says that it now has 10 collaborations on ADC projects and has generated more than $150 M in licensing fees to date -- with more milestones lingering out there as they products make it to market.  There are 11 ADCs in clinical development using Seattle Genetics technology. The latest Takeda extension validates the growing interest in the technology.  See Xconomy Seattle and Fierce Biotech.

 

Posted by Bruce Lehr March 15th 2011.

Geo Origin of Biotech's Next Blockbusters

This piece from Xconomy examines where the next generation of biotech blockbusters will come from relative to bio clusters (or elsewhere) in the US.  The article was speculating whether San Francisco would retain its perceived dominant position - you should read the article in full.

The qualifications a molecule needed to meet to be considered, included: completion of a pivotal trial, and have either received FDA approval or are clearly on that path.  The 8 nominees using that criteria:

• Human Genome Sciences' lupus drug (Benlysta)
• Vertex Pharmaceuticals drugs for hepatitis c (telaprevir) and cystic fibrosis (VX-770)
• Dendreon's prostate cancer drug (Provenge)
• Seattle Genetic's rare lymphoma empowered antibody (SGN-35 or brentuximab vedotin)
• Amgen's antibody (denosumab) for osteoporosis (Prolia) and cancer (Xgeva)
• Plexxicon and Roche's melanoma treatment (PLX-4032)
• Genetech/Roche's empowered Herceptin (T-DM1)

That's one from Washington DC, two from Boston, two from Seattle, one from greater LA, and two from the San Francisco bay.  Over and out.

 
Posted by Bruce Lehr March 14th 2011.

SeaGen Turns in FDA Application

Seattle Genetics turned in its FDA application for its antibody drug conjugate or "empowered antibody" known as SGN-35 or brentuximab vedotin for the treatment of Hodgkin's disease. 

SeaGen Turns in FDA Application.

It asked the FDA for expedited review - faster than the agency's usual six-month review period for such a treatment. It remains to be seen whether the agency will grant the expedited request.  SGN-35 would be Seattle Genetics first product on the market and it would be one of the first if not the first ADC to be approved if the expedited review is granted.

This one will be closely watched as the industry as a whole is expected to make more efforts with empowered anitibodies if SGN-35 and/or Genentech's T-DM1 gain agency approval.

 

Posted by Bruce Lehr March 2nd 2011.

ImmunoGen CEO Highlights Two New Souped-Up Antibodies Against Cancer

Immunogen wants the world to know about its other antibody-drug conjugate clinical programs - beyond Genentech's T-DM1 - to let everyone know they are alive and kicking. It's CEO will get the word out at an analysts conference today and at scientific meetings later this year.

ImmunoGen CEO Highlights Two New Souped-Up Antibodies Against Cancer.

On parade our two compounds, IMGN859 and IMGN529, for non-hodkin's lymphoma and folate receptor bearing cancers, like breast or ovarian, respectively. Immunogen plans to file an IND with the FDA in mid-2011 for a non-hodgkins trial.  IMGN529 will enter human testing in phase I trials for various cancers in early next year. 

I believe that ADCs will be important cancer drugs going forward and it will be important to keep abreast of these trials as they progress.

Posted by Bruce Lehr Feb 25th 2011.  

SAFC Touts Completion of First HP-API Projects at Verona, WI Site

SAFC has completed its first customer manufacturing projects in its Verona, WI site.  The site was built to manufacture high potency compounds (including anitbody drug conjugates) - many for Big Pharma projects applied to the oncology and infectious disease areas.

News from InformexUSA 2011: SAFC Announces Completion of First Projects at New Verona, WI Facility « SAFC Live.

The new Verona site, which began GMP manufacturing in June 2010, complements its SAFC sister site in Madison, WI and houses commercial scale reactors capable of producing up to 4000 L batches, or up to 10x the batch capacity of Madison. Verona is designed to offer late stage and commercial scale and is also Safebridge certified like Madison.

The high potency market is growing in double digits.  The Verona site is an example of SAFC's commitment to invest in key high-value technologies in growth markets.

 

Posted by Bruce Lehr Feb 17th 2011.

SeaGen Strengthens ADC Grip within Genentech

From Seeking Alpha, Seattle Genetics is increasing "in" and Immunogen increasingly "out" in ADC projects in Genentech.  Genentech recently advanced 3 more antibody drug conjugate (ADC) programs to phase I using the SeaGen technology.  This is in addition to another more advanced program for a CD22 ADC aimed at blood cancers.  Genentech has not confirmed the identity of the three programs but it is speculated that CD97b (lymphoma) and TENB2 (prostate cancer) are among them.

Beyond that, Genentech still has TDM-1 based on Immunogen technology and it has shown remarkable activity and a surprisngly benign safety profile. All of the Genentech ADCs employ non-cleavable linkers and Genentech appears to prefer the SeaGen technology for that purpose.  Genentech also seems to prefer targets where non-cleavable linkers can be used with success - which again points toward more Seattle Genetics projects if that trend continues.

 

Posted by Bruce Lehr Feb 16th 2011.

Seattle Genetics Raises $155M to Support Selling First Drug

As reported in Xconomy, Seattle Genetics has raised another $155 M through sale of its stock to fund the anticipated launch of its antibody drug conjugate SGN-35 - a so-called empowered antibody.  The money will go to hiring a "lot of people" to introduce the drug to the US market.

Seattle Genetics Reloads Cash Reserves With $155M, On Cusp of Selling First Drug.

SGN-35 or brentuximab vedotin was developed with Seattle Genetics partner Millenium (now owned by Takeda) and is aimed for use in treating Hodgkin's disease and anaplastic large cell lymphoma.  The drug has performed extremely well in phase III trials and its approval is much anticipated.

SeaGen stock has increased by nearly 60% in 2010 and it closed at $16.17 yesterday.  In it's offering, the company sold 10 million shares at $15.50 per share (dilution). The compnay also reported having $315.6 M on its books as of September 30th 2010.

Posted by Bruce Lehr Feb 2nd 2011.