Pullan Consulting
Biotech Business Development Consulting
lpullan@msn.com 805-558-0361
Issue #16
Pullan's Pieces
Commentary on Science & Business of Drug Development
For Business Development & Others
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Deal Averages.
A recent Nature Biotechnology (August 2007, p 859) cites Recombinant Capital on some average deal sizes. The average upfront payments and back-end payments were reported to be $6.5 million and $39 million for preclinical deals; $10 million and $55 million for Phase I deals; $17.5 million and $110 million for Phase II deals; and $70 million and $150 million for Phase III deals. Of course, the averages have very large ranges and cover diverse types of assets and deal structures. The free portion of the Recap website (www.recap.com) lets you see a number of analyses for a bit more feel, but it is still very hard to grasp what the averages represent without going deal by deal.
The US Patent and Trademark Office tapping the internet to find prior art.
The US PTO is starting an internet test with 250 patent applications, letting the public provide information on possible prior art. Prior art can mean a claimed invention is insufficiently novel and unobvious to warrant a patent. In the internet trial, participants will discuss the validity of claims by posting messages, uploading digitized prior art, and voting on the Peer-to-Patent site. The 10 best pieces of prior art that emerge through this process will be forwarded to the patent examiner at the US PTO. Software companies such as Sun, Microsoft, GE, IBM, and Redhat have all volunteered to have their patents examined via the Peer-to-Patent website. The PTO will compare the results with the independent searches conducted by the patent examiner. It is hoped that the process will reduce the spurious patents that lead to post-grant examinations and lawsuits, and perhaps reduce the backlog for examiners. 173,771 patent applications were approved in 2006 and there is a backlog of more than 800,000 patents. New submissions have a time from filing to first action of up to 52 months. http://www.technologyreview.com/Biztech/19419/
Polypharmacy the 5th leading cause of death in the US.
Drug-drug interactions from polypharmacy are responsible for up to 28 percent of hospital admissions and, if it were reported as the cause of death, would be the fifth leading cause of death in the United States. The average community-dwelling older adult takes roughly twice as many drugs as younger persons, 4.5 prescription drugs and 2.1 over-the-counter medications, and their physiology is less able to handle them. Often there is no single physician or pharmacist aware of all the drugs taken. (The New York Times, Sept 28, 2007).
Will continuous manufacturing replace batch manufacturing?
Novartis is paying MIT $65 million over 10 years to study how to change pharmaceutical manufacturing from repeated batches to a continuous process. (Fierce Biotech, Sept 28, 2007). For batch processes, the ingredients are added at the beginning of each cycle, and the product removed at the end of each cycle. Poor quality batches can be rejected or re-processed. In continuous manufacturing, new materials are added continuously and products are removed continuously; quality is assured by predetermined measurements throughout the process.
Expected benefits of continuous manufacturing include using smaller production facilities, with lower building and capital costs; minimizing waste, energy consumption and raw material use; and enhancing process reliability and flexibility to respond to market needs.
Why are drugs generally made in batches unlike the continuous processes used in other industries from automobiles to the oil industry? Most drug candidates are first synthesized in small batches in the lab. For many drugs, the quantities needed during clinical trials establishing efficacy and safety are quite small and can also be made with a batch process modeled on the lab process. The desire to get on the market rapidly to exploit the time without direct competition may also reduce investment in novel processes. Finally, manufacturing costs are a small proportion of the overall costs of getting a drug to the patient. FDA approval currently requires multiple validation batches of the final manufacturing process; changing the process substantially during development risks difficulties or delays with FDA approval. (However, the FDA has an initiative, “Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach”, to encourage continuous processes and other improvements. http://www.fda.gov/cder/guidance/5815dft.htm).
Biotech tour: Italy
Italian biotech is composed of 222 companies, with 4083 million Euros ($5.08 billion) in revenue. Italy has a foundation of quality science, ranking 7th in the world in highly cited publications in a 2004 Nature review. Several of the pharma companies have long histories, with Molteni founded in 1892, Indena in 1921 and Recordati in 1926. Most of the companies, including Menarini with ~ $2 billion in revenues, are private. There are few local VCs. However, in recent years, four Italian biotech clusters located in Lombardy, Piedmont, Tuscany and Friuli Venezia- Giulia, have promoted biotech by financing technology transfer agencies, incubators and supporting seed funds. Science and technology parks have been important for supporting start-ups, with 30% of the Italian companies located in biotech parks. In 2006, Gentium, BioXell and Newron Pharmaceuticals had successful IPOs. The new Italian Financial Law approved new incentives to encourage the biotech industry development with an insurance plan for bank loans and capital and a tax credit on research. (www.biotechdirectory.it)
Companies with drugs in clinical trials according to PharmaProjects include:
Abiogen Pharma – in Phase II: a MHC non-restricted cytotoxic T cell line for CML and other cancers, an MSH fragment for mycosis fungoides (a form of NHL). In Phase I: an osteogenic growth peptide, an immunotoxin of anti-CD22 and anti-CD19 conjugated to ricin for NHL, and an iron-cholic table for iron-deficiency-related anemia.
Angelini – in Phase II: a chemokine synthesis inhibitor as an anti-inflammatory for diabetic nephropathy.
Chiesi – in Phase II: an NMDA and MAO inhibitor (with Vernalis) for neuropathic pain, an M3 antagonist for asthma. In Phase I: a SERM for osteoporosis, an inhaled b2 agonist and a corticosteroid for asthma (SALVAT has co-marketing rights for Central America and Spain).
Cosmo Pharmaceuticals – in Phase III: an oral colonic-release formulations of the steroid budesonide for IBD, a low molecular weight heparin for ulcerative colitis, and a semisynthetic antibiotic rifamycin SV for infectious traveler’s diarrhea.
Dompe - in Phase II: an IL-8 antagonist selective for CXCR1 and CXCR2 receptors for post-ischemic reperfusion injury and the prevention of delayed graft function after transplant
Eurand – in Phase I: a once-daily Diffucaps formulation of ondansetron for nausea and vomiting
Genextra – in Phase II: an oral FxR agonist for the treatment of primary biliary cirrhosis and non-alcoholic steatohepatitis
Indena – in Phase II: (with Spectrum) a semisynthetic taxol anticancer agent.
Italfarmaco - in Phase II: an oral suppressors of TNF-alphaIL-1β biosynthesis for AML and myeloma.
Keryos – in Phase I/II: a recombinant methionyl GCSF for prevention of neutropenia
Menarini – in Phase III: an anti-idiotype antibody that mimics the ovarian cancer antigen CA 125, and a 2nd-generation tissue plasminogen activator (tPA) thrombolytic. In Phase II: an NK-2 receptor antagonist for IBS, an NK-2 receptor antagonist for asthma, and a synthetic 3rd-generation topoisomerase II inhibitor for solid tumors.
MolMed - in Phase II: (with Takara Bio for Asia) an autologous Tcell MAGE-3 and HSV TK cancer vaccine for melanoma and other tumors, a modified form of TNF-alpha fused to the angiogenic targeting peptide NGR for cancer, and (again with Takara Bio) a HSV-tk gene therapy for the prevention of graft-vs-host disease.
Molteni Farmaceuitici – in Phase I: an antibiotic/antifungal for dermatological infections and oral candidosis.
Nerviano Medical Sciences – in Phase II: a doxorubicin derivative for primary liver tumors, a DNA minor groove binding derivative of distamicin A for sarcomas ( with Cell Therapeutics) and an aurora kinase inhibitor for CML, and in clinical trials: a CDK inhibitors for cancer.
Newron – in Phase III: a sodium and calcium channel antagonist, glutamate release inhibitor, MAO-B inhibitor and dopamine uptake inhibitor as an anticonvulsant and antiparkinsonian (licensed to Merck Serono) and a voltage-gated sodium channel blocker for chronic pain.
Philogen – in Phase II: an antifibronectin antibody fragment conjugated to radioactive 131I for targeted radiotherapy of cancer (with Bayer).
Recordati – in Phase II: a 5-HT1A antagonist for overactive bladder and urinary incontinence.
Rottapharma – in Ph III: the active enantiomer of the CCK-A antagonist loxiglumide for IBS. In Phase II: a K channel agonist for bronchial asthma, COPD and allergic rhinitis, and a CCK-B receptor antagonist for anxiety and panic attacks. In Phase I: a glycine site NMDA receptor agonist as an antipsychotic (Xytis has a license).
Sigma-Tau – in Phase III: cysteamine hydrochloride eye drops for corneal cystine accumulation. In Phase II: intra-operative avidination for radioisotope therapy for breast cancer, an oral camptothecin derivative for cancer (Novartis has rights), a Na+/K+-ATPase inhibitor for heart failure (Debiopharm has rights), a steroid-based renal Na+/K+-ATPase inhibitor for hypertension in patients with an adducin gene mutation, and a carnitine-related palmitoyltransferase inhibitor for Type II diabetes. In Phase I: an pretargeted antibody radioimmunotherapeutic, a camptothecin derivative, and an adamantyl retinoid derivative, all for cancer.
SPA (Societa Prodotti Antibiotici SPA) - in Phase II: a polyene for mycosis (Kaken is a licensee).
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Pullan Consulting
Linda M. Pullan, Ph.D.
Biotech Business Development
lpullan@msn.com
805-558-0361
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