When It Rains It Pours...

And the Colorado M&A hits keep on coming…Merck & CO. (NYSE: MRK) announced the $1.1 billon acquisition of San Francisco headquartered Sirna Therapeutics, Inc. (NASDQ: RNAI).

Why does an acquisition story about an acquirer from New Jersey and an acquiree from San Francisco make it onto the virtual pages of Colorado Life Science Deal Flow you may ask? Well…

The story begins back in Boulder, CO, circa early-eighties, when then CU-Boulder biochemistry professor turned Nobel Prize winner (1989) and current Howard Hughes Medical Institute President, Thomas Cech, Ph.D. demonstrated how, using the Tetrahymena model organism, RNA could fold into complex shapes and catalyze biochemical reactions, a function previously thought to be restricted only to protein enzymes. This discovery led to the founding of Ribozyme Pharmaceuticals, Inc. (RPI) in 1992, where the catalytic properties of the “Ribozyme” would be designed as a therapeutic approach to target and cleave specific mRNA’s in specific diseases.

Tetrahymena - Where it all began
Courtesy of the Albert Einstein College of Medicine - Yeshiva University

As the fate of science, technology and innovation would have it the cellular mechanism RNA interference (RNAi) emerged as an extremely specific method for targeting mRNA’s and inhibiting gene expression. Thus RPI was in part reorganized as Sirna Therapeutics, Inc. in 2002 to focus pursuit upon the short interfering RNA (siRNA) technology and current CEO Howard Robin & Co. have subsequently continued to further build out a potent IP portfolio, become the first company to bring a chemically optimized siRNA into clinical trials, and have demonstrated stability, circulation, tissue targeting, cellular activity and immune response efficacy in their preclinical compounds. Shortly after the reorg the city of San Francisco presented an opportunity to then Boulder-based Sirna that could not be refused and if I am not mistaken all but the cGMP manufacturing facility packed up and headed West.

So on the heels of Gilead-Myogen and Endo-RxKinetix, the Merck-Sirna deal perhaps catapults the 2006 bio deals to the level of historic; and further validates the strength of the universities, IP, talent and investors in Colorado. But shhhh…I have reason to believe that this is just a taste of what is to come.

Move Over Macugen, Visudyne & Lucentis?

Sirna Therapeutics, Inc. (Nasdaq: RNAI), reported the final results from its completed Phase I trial for Sirna-027, a novel therapeutic for age-related macular degeneration (AMD). The Phase I study evaluated the safety, tolerability, and biological effect of single-ascending doses of Sirna-027 in patients with AMD. A total of 26 patients with active disease were enrolled to receive a single intravitreal injection of Sirna-027.

Single doses of Sirna-027 were safe and well tolerated, and all 26 patients (100%) showed visual acuity stabilization eight weeks after a single injection.

In addition, 19% of patients experienced clinically significant improvement in visual acuity. Three months after a single injection 92% of patients showed visual acuity stabilization, with 15% of patients experiencing clinically significant improvement in visual acuity. Importantly, a decrease in foveal thickness was observed in some patient groups, which is an indication of biological activity of Sirna-027 and chemically optimized siRNA's.

A Phase II trial is expected to initiate later this year.

Calling All Quants!

Do not miss out on the Colorado Bioscience Association Finance Seminar on 27 July. Topics to be covered include accounting issues associated with stock compensation, and valuation issues incoporating Black-Scholes and lattice models.

Register (here)

Big Sky Venture Capital Conference

Do not miss out on the 2nd Annual Venture Conference for the Northern Rockies, to be held on 24-25 August. The deadline for presenting companies at the Big Sky Venture Capital Conference is fast approaching.

Deadline for submission: July 31st.

There is a biotech track for companies seeking seed stage funding through mezzanine. Companies from Colorado are welcome to participate.

For more information click (here)

Sirna Shaking It Up

Lot’s of news coming from Sirna Therapeutics Inc., this Monday morning. First RNAI announced today that the USPTO will issue U.S. Patent No. 7,022,828 on April 4, 2006. This is the first siRNA target patent issued in the United States and sets an important precedent for Sirna's entire target patent portfolio.

The patent covers any chemically modified siRNA targeting I Kappa B kinase-gamma (IKK-gamma). Importantly, the claims of the patent are not limited to a specific siRNA sequence but cover any siRNA sequence used against the gene. In addition, the claims of this patent are not limited to a specific type of chemical modification or structure but cover any chemical modification that can be made to the siRNA. The patent covers blunt-ended siRNAs as well as those with one or more nucleotide overhangs. IKK-gamma is an activator of the NF-kappaB pathway (NF-kb), an important mediator in a host of diseases, such as asthma, arthritis, cancer, chronic inflammation, neurodegenerative diseases and heart disease.

Secondly, GlaxoSmithKline said it will pay Sirna a $12 million upfront, and potentially more than $700 million in milestones, to enter into an exclusive multi-year alliance focused on discovery, development and commercialization of novel RNA interference therapies for respiratory diseases. The street responded quite well to these announcements in pre-market and are sustaining enthusiasm as the trading day continues.

Sirna Granted Patent for RNAi Production

Sirna Therapeutics, Inc. (Nasdaq: RNAI), announced today that the U.S. Patent and Trademark Office has granted Patent No. 6,989,442 for the chemical synthesis and manufacturing of ribonucleic acids. The patent broadly covers a process for the synthesis, deprotection and purification of nucleic acids with one or more ribonucleotides.

This process is critical for the efficient synthesis of RNA at high yields and high purity and is applicable to both small- and large-scale production of oligonucleotides such as siRNAs and aptamers. The patent further expands Sirna's leadership position in the area of synthesis and manufacturing of GMP quality RNA which is required for both chemically modified and unmodified siRNA-based therapeutics.

Sirna now holds 48 issued patents with an additional 240 plus patent applications still pending.

In order to manufacture siRNA it takes a synthesis protocol encompassing some 150 steps. This newly issued patent covers the required steps to manufacture siRNA material that achieves not only yields in excess of 60% but of unparalleled quality too.

Sirna to Webcast JP Morgan Presentation

Sirna Therapeutics, Inc. (Nasdaq: RNAI), is scheduled to present at the 24th Annual JPMorgan Healthcare Conference on Wednesday, January 11, 2006 at 4:00 p.m. PST. A live audio webcast of the presentation will be available at the Company's web site at www.sirna.com.

Sirna is a clinical-stage biotechnology company developing RNAi-based therapies for serious diseases and conditions, including age- related macular degeneration (AMD), hepatitis B and C, dermatology, asthma, Huntington's disease, diabetes and oncology. Sirna Therapeutics has presented interim Phase 1 clinical trial data for its most advanced compound, Sirna-027, a chemically optimized siRNA targeting the clinically validated vascular endothelial growth factor pathway to treat AMD. Sirna-027, which has been partnered with Allergan, Inc., continues to demonstrate that it is safe and well tolerated with 100% of patients showing visual acuity stabilization after eight weeks from a single injection. In addition, Sirna recently announced that it has selected Sirna-AV34, a systemically delivered, optimized siRNA compound, as its candidate for advancement to human clinical testing against Hepatitis C virus.

Sirna Setting the Stage

Sirna Therapeutics (NASDAQ: RNAI) rocketed yesterday, though naturally some profit taking is occurring today, following very encouraging news of the first demonstration of systemic siRNA efficacy at therapeutically relevant doses, results were published in Nature Biotechnology.

The study demonstrated that Sirna's chemically optimized and encapsulated siRNAs have high potency and prolonged duration of activity in vivo. The siRNA formulation, targeting Hepatitis B Virus, was administered by standard intravenous injection to mice carrying replicating HBV. Three therapeutically relevant doses of 1, 3, or 5 mg/kg resulted in up to a 95% dose dependent reduction in serum HBV DNA levels.

RNA interference (RNAi) is a natural, selective process for turning off genes. RNAi is triggered by short interfering RNA (siRNA) molecules that engage a group of cellular proteins, known as RISC (RNA induced silencing complex). The RISC guides the siRNA to its target messenger RNA (mRNA, the messenger between DNA and proteins) by complementary base pairing for the targeted break-up of the mRNA thus halting protein expression or viral replication. The RISC-siRNA-complex binds and cleaves multiple mRNA molecules in a catalytic fashion.

Sirna Therapeutics recently moved their corporate headquarters to San Francisco though R&D, manufacturing and administrative facilities remain in the Boulder, CO campus.

I’ve been a longtime shareholder of RNAI and have never been more excited about what lay ahead.