Insmed Gets First FOB Clinical Study Greenlight!

An important milestone for Insmed (NASDAQ: INSM), developer of follow-on biologics and biopharmaceuticals, was achieved in the form of approval from the UK's Medicines and Healthcare products Regulatory Agency to initiate their first clinical study for INS-19, a follow-on biologic product candidate. INS-19, is a recombinant form of human G-CSF, is a follow-on biologic of Neupogen®. Amgen (NASDAQ: AMGN) booked 2007 sales of Neupogen® that approached $900M, and the patent expires in 2013.

The Phase I study will be conducted in the UK and will compare the safety and establish the bioequivalence of INS-19 to Neupogen®. Results from the trial are expected in 2H08, and are planned to be used as part of a submission to the FDA to establish a protocol with the agency for a Phase III trial in the U.S.

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Amgen: Denosumab, Part III

CLSDF has been paying particular attention to the clinical development of Amgen’s (NASDAQ: AMGN) Denosumab, a monoclonal antibody that targets RANK Ligand, the essential mediator of osteoclasts - the cells that break down bone (Read Part I HERE and Part II HERE). Now, pivotal Phase III data shows Denosumab increased bone density at multiple skeletal sites in early and later-stage postmenopausal women.

Results from a 24-month, 332-patient Phase III pivotal study in women with early and late-stage postmenopausal osteoporosis was published in the Journal of Clinical Endocrinology and Metabolism. In this study, twice-yearly subcutaneous injections of Denosumab increased bone mineral density (BMD) at all sites measured, including in highly cortical areas of the skeleton. Cortical bone comprises 75 percent of skeletal mass and is a primary determinant of overall strength in vertebral and non-vertebral sites throughout the skeleton. Denosumab treatment significantly increased lumbar spine BMD compared with placebo and also produced significant increases in BMD at the hip, wrist, and total body.

Amgen expects the results of its large, pivotal Phase III registrational study, which will evaluate Denosumab's impact on fracture risk reduction, in women with postmenopausal osteoporosis, in the 2H08.

Next week we should have an update on Amgen’s oncology pipeline of five investigational compounds AMG 102 (a fully human monoclonal antibody that targets the action of hepatocyte growth factor/scatter factor), 386 (a recombinant Fc-peptide fusion protein (peptibody) targeting angiopoietins), 479 (a fully human monoclonal antibody that binds to insulin-like growth factor-1 receptor without cross-reacting with the closely related insulin receptor), 665 (a fully human monoclonal antibody agonist directed against Death Receptor 5) and 706 (Motesanib diphosphate is a highly selective, oral agent that is being evaluated for its ability to inhibit angiogenesis and lymphangiogenesis by targeting vascular endothelial growth factor receptors 1, 2 and 3).

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Insmed: A Going Concern…

It is often a challenging path to be first to market. Insmed (NASDAQ: INSM) is blazing that trail via their aim to be the first US-based biotechnology company to develop a comprehensive portfolio of Follow-on Biologics (FOBs). From my understanding, one such challenge the company faces is that no regulatory pathway currently exists for FOBs, which are also commonly referred to as biosimilars or biogenerics, in the US, though a regulatory system for approving FOBs was established in Europe in 2006. As many a successful company in the life science space has done is avoid being a one-trick pony by diversifying the product portfolio. Insmed subscribes to this asset diversification strategy with incorporation of their proprietary protein platform (say the five times) that focuses upon niche markets with unmet needs.

Insmed announced, in order to remain compliant with NASDAQ rules and regs, a going concern audit opinion was submitted with the most recent 10K SEC filings. This going concern audit opinion was given because the Company’s ability to continue as a going concern is dependent upon its ability to raise capital through securities offerings, debt financing and partnerships to fund on-going operations. Since mid-December 2007 the share price has been trading below $1.00 thus setting off various warning bells.

Interestingly the London-based I-Bank Collins Stewart (which many of you Coloradoan’s may recall acquired C.E. Unterberg Towbin in 2007 who had offices in LoDo) has begun coverage of Insmed and issued this valuation not two weeks ago…

By applying a 6-7x multiple to our 2012 revenue forecast of $88.7MM and discounting back at a rate of 20% per annum, we arrive at a fair value for INSM shares of $2.

I am most interested to hear if Collins Stewart has any direct or indirect relationships with Insmed and if not then why then have they initiated coverage and their BUY recommendation? Collins Stewart covers a number of other public companies with Colorado roots or ties including Allos Therapeutics (NASDAQ: ALTH), Array Biopharma (NASDAQ: ARRY) and OSI Pharmaceuticals (NASDAQ: OSIP).

With Insmed’s cash position as-of 31 December 2007 at approximately $16.5M combined with the planned initiation of clinical trials this year for INS-19 and INS-20 [generic versions of Amgen’s (NASDAQ: AMGN) Neupogen and Neulasta] combined with ongoing Phase II enrollment for the proprietary IPLEX™ asset myotonic muscular dystrophy study, at least IMHO the current cash position does not compute with ongoing needs.

Just an interesting aside…if I am not mistaken the Insmed manufacturing facility in Boulder is across the street from the Amgen site…hmmm?

So, it is unambiguous that there is continuing developmental risk here if a financing event in the form of debt, equity or partnership is not achieved, I would venture to guess based-upon an anticipated ramp in quarterly burn, some time this year. Let’s keep our fingers crossed that management is able to get a deal done and soon!

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Denosumab: 2 Trails Down 7 To Go…

Most recently Amgen (NASDAQ: AMGN) announced the second successful Phase III trial for Denosumab (manufactured in Longmont, CO) osteoporosis study, which met all of its primary and secondary bone mineral density (BMD) endpoints in a head-to-head comparison with Merck’s (NYSE: MRK) Fosamax® in post menopausal women. Back in December of ‘07 CLSDF set the Amgen-Denosumab table, read more (here).

In this second study, Denosumab treatment achieved significantly greater BMD gains at the total hip, hip trochanter and distal radius compared with Fosamax®. For the primary endpoint, the relative magnitude of BMD improvement at the total hip was approximately 40% greater in the Denosumab versus the Fosamax® group.

With two trials down there are five ongoing active Phase III trials:

1. A Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects with Low Bone Mineral Density
2. A Pilot MicroCT Study to Estimate the Effect of Treatment with Denosumab and Fosamax® in Postmenopausal Women with Low Bone Mineral Density
3. A Study to Evaluate Safety and Efficacy of Transitioning Therapy from Fosamax® to Denosumab in Postmenopausal Women With Low Bone Mineral Density
4. A Study to Evaluate Denosumab in the Prevention of Postmenopausal Osteoporosis
5. A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months)

And there are two final PIII studies that are still in the recruitment and enrollment stage:

1. A Study to Evaluate the Adherence, Preference, and Satisfaction of Denosumab and Fosamax in Postmenopausal Women with Low Bone Mineral Density
2. A Study to Evaluate the Long Term Safety and Sustained Efficacy of Denosumab in the Treatment of Postmenopausal Osteoporosis
   

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Source MDx: And the Band Played On...

CLSDF previously highlighted Source MDx, read the post (here)…there is nothing hotter than incorporating validated biomarkers under the umbrella of personalized medicine and that is what continues to transpire at the Source MDx Boulder headquarters. An impressive list of partners and clients of Source MDx include Abbott Labs (NYSE: ABT), Amgen (NASDAQ: AMGN), Celgene (NASDAQ: CELG), Eli Lilly (NYSE: LLY), and Pfizer (NYSE: PFE), to name a few. Now long time partner Pfizer has agreed to a new multi-year collaboration to incorporate the Source MDx platform into the Pfizer cancer and inflammation development programs. So that may be associated with one or more molecules in the Pfizer rheumatoid arthritis, transplantation rejection, osteoarthritis, breast, lung, pancreatic, and colorectal cancers, melanoma and thryroid neoplasm development work. I have not delved into the Q’s or K’s to unearth details, can anyone leave a comment about specifics on these programs at Pfizer?

Particulars on the deal are not plentiful but it appears to be a multi-year collaboration where validated candidate biomarkers will lead to joint commercial opportunities for potential companion diagnostics. So at some point in the future expect to hear about one or more predicative biomarkers in the clinic. Source MDx shall receive 1) an equity investment 2) a technology licensing fee and 3) R&D funding over the term of the agreement. Source MDx shall retain certain commercial rights to diagnostic biomarkers discovered through the agreement and, co-commercialization of any companion diagnostics that are developed as part of the collaboration is likely.

***Update*** Looks like GlobeImmune is in the lead to win CLSDF-Reader's Company of the Year award. Be sure to cast your vote at http://CLSDF.com. Voting ends 31 January!

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Amgen: Denosumab, Positive PIII Results

From my understanding Amgen (NASDAQ:AMGN) is manufacturing denosumab (AMG162) at the Longmont, CO facility and announced results from the first Phase III pivotal study of the monoclonal antibodies effect on bone density across the skeleton in women with non-metastatic breast cancer who were receiving adjuvant Aromatase Inhibitor therapy (AI’s lower the amount of estrogen in post-menopausal women who have hormone-receptor-positive breast cancer). Bone loss is an adverse effect of AI therapy. Results from the Phase III study demonstrated that denosumab increased bone mineral density and cortical bone worsened by AI therapy.

Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets Rank Ligand, the essential mediator of osteoclasts by working to inhibit all stages of osteoclast activity. Rank Ligand is found in all parts of trabecular and cortical bone and Rank Ligand inhibition represents a highly targeted and specific approach to treating osteoclast-mediated bone destruction.

The competitive landscape for denosumab’s blockbuster potential is a fierce $7B/yr osteroporosis market led by:

• Novartis’ (NYSE: NVS) Reclast®/Zometa® ($1.3B 2006 sales, though this is for all indications of the drug), and
• Merck’s (NYSE: MRK) now off patent Fosamax ($1.4B 2007e).

Looking at the AMGN clinical trails site (which is a great site by the way!) it appears as though there are seven additional ongoing Phase III denosumab studies, two of which are still recruiting. An NDA is planned for filing in 2009. Some believe that denosumab could garner upwards of $2B per year; needless to say that would certainly turn about the fortunes of the battered share price and if AMG785, a Sclerostin antibody, continues to proceed through its Phase I trial could function to reinforce Amgen’s potential dominance in bone mineral density for many years to come. Taking a look at the 5-year chart I am wondering if this does not present approaching perhaps the best buying opportunity in more than five years, though a bottom does not yet look apparent? Not that this is investment advice of any kind…


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Between the Lines: Amgen Manufacturing

Amgen (NASDAQ: AMGN) announced that the company has decided to postpone indefinitely its planned design and build-out of a bulk manufacturing facility in Cork, Ireland.

Amgen has two manufacturing facilities in Boulder and Longmont, Colorado. Longmont is responsible for bulk manufacture of Epogen and Aranesp. Boulder manufactures Kineret, Kepivance and a number of product candidates in late-stage clinical development.

Capacity at the Boulder facility was recently increased; combine this with Cork coming off line and it may be safe to say that the Amgen-Colorado imprint shall continue to thrive.

For more CLSDF coverage on the Amgen and Colorado connection click (here).

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3 Commercialized Products & Counting!

QUESTION: What do ZostaVax®, Kineret® and Macugen® have in common…

ANSWER: They are all FDA approved first-in-class commercialized products originating from University of Colorado intellectual property.

Want to learn more about these products and the rich product pipeline portfolio at the University of Colorado? Then take a listen to this podcast featuring David Allen, Ph.D., Associate Vice President, CU Technology Transfer Office speaking at the Holland & Hart Bioentrepreneur Club and observe the year-end performance metrics through July 2007 (here).

ZostaVax® is a vaccine developed by Merck & Co. (NYSE: MRK) which has been shown to reduce the incidence of Shingles (herpes zoster) by over 51% in a pivotal phase III study of 38,000 adults aged 60 and older who received the vaccine.

Macugen® is for the treatment of neovascular (wet) age-related macular degeneration. It was developed by EyeTech Pharmaceuticals who was recently acquired by OSI Pharmaceuticals (NASDAQ: OSIP) and licensed to Pfizer (NYSE: PFE) for late stage development and marketing.

Kineret® developed by Amgen (NASDAQ: AMGN) for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed 1 or more disease-modifying antirheumatic drugs.