Pullan Consulting
Biotech Business Development Consulting
www.pullanconsulting.com and www.lindapullan.com
email: lpullan@msn.com 805-558-0361
Issue #38, August 2009
Pullan's Pieces
Commentary on Science & Business of Drug Development
For Business Development & Others
Cell Therapy for Cancer – J&J does a CRADA; a status report on cell therapies in the pipeline
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J&J (Ortho) announced a 5-year CRADA (Cooperative Research and Development Agreement) with Steve Rosenberg of the NCI to run a melanoma clinical trial using autologous (where the cells come from the same patient) cytotoxic T lymphocytes (CTLs). There will also be work together on a T cell receptor program. http://www.jnj.com/connect/news/all/20090605_090000 With J&J funding trials on autologous cell therapy for cancer, I thought it was time for to look at cell therapies in the development pipelines for cancer. Historically, autologous therapies (where the patients own blood or tumor is expanded, treated and returned to the same patient) have been seen by big pharma as less like a drug in a bottle than a surgical procedure, and the complicated business model has been explored only by small companies.
A lack of big pharma activity is still apparent today. Sixteen autologous cancer vaccines are in Phase I and beyond, according to Pharma Projects. 5 are in Phase III or beyond. AVAX has approval in Australia for its haptenized melanoma cell vaccine, in Phase III in the US. Northwest Biotherapies has filed in Switzerland for its dendritic cell vaccine for glioblastoma and expects to file in the EU and US later this year. Northwest also has a Phase III dendritic cell vaccine for prostate cancer. Dendreon plans to submit an amended BLA for its dendritic cell vaccine for prostate cancer in the 4th quarter of this year, with data from the SPA (Special Protocol Assessment) Phase III trial. Accentia Biopharmaceutical is in Phase III with its anti-idiotype NHL vaccine. Its anti-idiotype antibody is an antibody designed to mimic the NHL antigen epitope and get an antibody response that recognizes NHL cells. Only 1 autologous clinical stage program has a large pharma partner. Kyowa Hakko Kirin is partnered with Argos Therapeutics for the RNA-pulsed dendritic cell vaccine in Phase II in renal cell carcinoma.
Heterologous cell therapies (where the cells can be from a pool of donors or from cell lines) seem to be more like the drug in a bottle business of pharmaceutical companies, but there are few in clinical development for cancer. There are 6 heterologous cell therapies listed as in Phase I and beyond. 2 are in Phase III or beyond. Both have large company partners. Osiris Therapeutics, partnered with Genzyme, has submitted a rolling BLA for its expansion of mesenchymal stem cells for graft versus host disease (GVHD) after bone marrow transplant in cancer patients. Gamida and Teva have a Phase III program with the use of cord-blood expanded CD34+ stem cells for hematopoietic reconstruction in hematological malignancies.
Signs of optimism: an IPO, new public stock offerings; a BIO and Thomson Reuters survey; Cooley Goodard on private company financings
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Cumberland Pharma filed an IPO, the first new biopharma offering in almost two years. Talecris Biotherapeutics has expressed an interest in filing a billion-dollar IPO. Seattle Genetics is raising $118 million from a new stock offering. Inspire Pharmaceuticals’ offering raised $115 million.
A survey (http://www.bio.org/edocs/BIO_ThomsonReuters09_study.pdf) of 80 biotech analysts, investors, and portfolio managers found that 64% said now is a good or very good time to invest in biotech. 2/3rds expect more M&A. Despite concerns about R&D productivity, 30% saw upcoming approvals as a catalyst for investment performance in the sector. Analysts saw oncology as the therapeutic area offering the best investment opportunities. Cash and management are among the key factors in looking at investments in the biotech sector.
As shared in PE Hub (http://www.pehub.com/47219/green-shoots-in-company-financings/), Cooley Goodard reported that the median pre-money valuations for private company (not just biotech) financings in the 2nd quarter were up from the prior two quarters, and that is true for A thru D+ rounds. Up rounds were an increasing percentage (but still a minority). The Cooley Goodard report has lots of stats on investor preferences for private financings.
Genomic sequence conservation does not always imply critical function
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We have come to think that when a gene is conserved, it means it is likely to have an important function, critical to the survival of the organism. If a sequence has fewer mutations than others, the difference has been ascribed to “constraint”, meaning mutations were rejected during evolution because they reduced the organism’s fitness. But this is simplistic according to an overview in Science (Don Monroe, July 10, p142-143).
Not all conserved sequences are important and not all important sequences are conserved. A study found that ultra-conserved sequences could be deleted from the mouse genome without killing the animals. The ENCODE study estimated 5% of the human genome is constrained to some extent, but only 25% to 30% of these were protein coding. Most of the rest were transcribed into RNA. But the ENCODE team could find no biochemical activity (such as binding transcription factors or epigenetic changes) on 15% of the constrained sequences. That this is not a mere lab artifact was suggested by the work of Zhang and colleagues, who found no correlation between the degree of conservation in sequence and function even for yeast genes that proved essential in 400 highly varied conditions.
Conservation may exist only because selective pressure over all the span of evolution just has not been enough to get rid of them. It is also not always true that clearly important genes will be more constrained than unimportant genes. The ENCODE studies have found a large portion of functional sequences have no evidence of evolutionary constraint. Comparing across many species may indicate some of these are lineage specific and others may be unconstained due to amazing redundancy in biology. Subtle constraints in sequences may also be due to effects not visible in the protein itself but in other intermediate effects such as on mRNA stability, or DNA binding protein interactions with the DNA sequence.
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Pullan Consulting
Linda M. Pullan, Ph.D.
Biotech Business Development
www.pullanconsulting.com and www.lindapullan.com
e-mail: lpullan@msn.com
805-558-0361
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