Accium Biosciences Inc.

Accium Biosciences provides accelerator mass spectrometry services to pharmaceutical customers for preclinical and early clinical pharmacokinetic and bioavailability analyses of candidate drug compounds. It is currently the only US commercial AMS supplier with an in-house instrument.

Building the first commercial US core facility for accelerator mass spectrometry

550 17th Avenue, Suite 550

Seattle, WA 98122

Phone: [phone]

Fax: [phone]

Web Site: www.acciumbio.com

Contact: Ali Arjomand, PhD, President & COO

Industry Segment: Drug Development Services

Business: Mass spectrometry services for preclinical and early clinical testing

Founded: May 2004

Founders: Ali Arjomand; Michael Chansler, VP, Business Development & Sales

Employees: 8

Financing to date: $3.4 million

Investors: WRF Capital; Sabey Corp.; Private investors

Board of Directors: Glenn Kawasaki, PhD, CEO; Ali Arjomand; Ed Eadeh, VP, Strategic Development; Loretta Little (WRF Capital)

Scientific Advisor: Nenad Sarapa, MD (Daiichi Sankyo Co. Ltd.)

The idea of using accelerator mass spectrometry (AMS) as an analytical tool for drug development arose largely from work in the nutrition department at the University of California, Davis in the mid-1990s, which collaborated with the AMS team at the Lawrence Livermore National Laboratory (LLNL). Ali Arjomand, a doctoral candidate in a lab at UC-Davis at that time, was part of that work. Six years after leaving the school, Arjomand founded Accium BioSciences Inc. to provide AMS to pharmaceutical customers for preclinical and early clinical pharmacokinetic and bioavailability analyses of candidate drug compounds.

Part of Arjomand's PhD work focused on analytical chemistry methods development. His lab, headed by Andrew Clifford, PhD (and which for many years also included Stephen Dueker, PhD, founder of Vitalea Science Inc. (see "Vitalea Science Inc.," in this issue) , was looking at the metabolism, kinetics, and bioavailability of vitamins in humans, to better ascertain specific dietary requirements for them.

"There were many approaches to the problem," Arjomand explains, including steady-state analyses that matched up the dietary intake of a vitamin with its output, as well as indirect approaches using animal models or population-based epidemiological studies. "We had good analytical techniques," he says, but they were not sufficiently sensitive to differentiate a vitamin taken as a pill and measured in blood from what came from the diet.

Around that time, John Vogel, PhD, a senior scientist at LLNL's center for accelerator mass spectrometry, visited Clifford's lab to discuss the notion of using carbon labeling (specifically the carbon isotope 14C) for biological studies. "LLNL wanted to broaden the range of applications for AMS," recalls Arjomand. With the urging of Andy Clifford, Arjomand shaped part of his dissertation around the design of a long-term study the lab was conducting in collaboration with LLNL's Vogel of 14C-tagged folic acid, to quantify the bioavailability, biodistribution, excreta, and pharmacokinetics of a single dose.

Following a half decade working in the biotech industry, Arjomand returned to his AMS roots to form Accium, to apply AMS to the preclinical and clinical analysis of candidate drugs. "In that four- to five-year period I was building a business model around AMS," Arjomand says. Meanwhile, John Vogel was pursuing expanded uses with some companies, and the AMS-oriented UK start-up Xceleron Ltd. was gaining traction, first as a program at York University in the UK funded by several Big Pharmas (between 1998 and 2001 it received contributions from Glaxo Wellcome, Pfizer Inc. , Novartis AG , and Janssen Pharmaceutica NV ), and eventually as a stand-alone firm.

"The York University facility introduced the notion of microdosing as a way to get early clinical data," says Arjomand. Microdosing studies—which use less than 100 micrograms of drug and are performed in healthy volunteers--give drug developers additional information on kinetics and biodistribution, making them less dependent on animal models for dosing information. The hope is that such data will help in the prioritization of compounds for initial human testing. AMS offers greater sensitivity than other techniques used in microdosing studies, such as the non-radioisotope method LC-MS-MS (liquid chromatography/mass spectromety/mass spectrometry).

Although the chemistries needed to label 14C may be tricky (and costly) depending on the drug molecule and the metabolic process to be measured, AMS can be used to detect drug amounts in urine, fecal, blood, or tissue samples. "It's easy to do detailed kinetic studies with multiple time points," Arjomand notes. In some cases, AMS enables a more complete identification of the path of metabolites as the drug is processed. Plus, only very small sample amounts are needed: the blood draw needed for AMS is only a pin prick: "Each measure is only 20 microliters of plasma," he says. The amount of radiation needed for AMS is also tiny: "It's about the same as the radiation exposure on a four-hour airplane flight," says Arjomand. "Just slightly above background."

Arjomand pulled the trigger and started Accium in 2004, raising $3.4 million of initial funding with a mix of debt and cash. "It took a while to find investors with the right risk profile," he says, adding that the business model was not appropriate for most venture capitalists. "It's a service business, and the size of the deal wasn't large enough for a lot of VCs, but at the same time it was too large for angels." Endorsements by regulators—first the European Medicines Agency (EMEA) in 2003, and later the FDA---for the use of microdosing studies prior to full IND filing also helped. "The underlying technology was there," says Arjomand. "What the statements by FDA and EMEA allowed us to do was to get funding." Indeed, "the notion of microdosing got investors excited," he goes on. "You rarely see innovations in clinical development."

In the fall of 2004, Accium ordered an AMS, which was installed in January 2006 according to Arjomand. He and co-founder Michael Chansler, Accium's VP, business development and sales, have spent the last year developing the customer base and planning for launch. They signed on one client, a small Seattle biotech, for a preclinical study of a potential small-molecule drug for diabetes, using LLNL's AMS to do the detection. (John Vogel's team at LLNL has patented methods for using AMS for biomedical applications, and it has licensed its technology on a non-exclusive basis to Accium, as well as to Vitalea and Xceleron.)

Despite the resources offered at LLNL or by Xceleron in Europe, some clients prefer to wait for a commercial provider in the US, Arjomand claims. "Clients often want their own QA [quality assurance] to have access to the lab," he contends. "Auditing books and training logs, and other elements of GLP [Good Laboratory Practices] are more difficult at LLNL because it is not a commercial provider." As a result, he expects clients who have done pilot work at LLNL to gravitate to Accium. "We're taking advantage of being the first to bring this technology to the US commercially. With the FDA guidance out, our timing couldn't be better." The expected demand is sufficient, he says, "to fill our pipeline nicely." Accium's in-house AMS will have sufficient capacity to take the company to breakeven in 2006, Arjomand adds.

Accium foresees a three-tiered market for its services: preclinical studies, microdosing studies conforming to the newly issued FDA final guidance on Exploratory INDs (so-called Phase 0 trials), and "straight-up" Phase I studies at full dose, where the investigational drug is tagged and administered separately--"either sequentially or piggybacked with the same trial," Arjomand says. For the most part, he expects clients to design the studies and arrange for the preparation of the 14C-tagged drug: "They know the questions they're attempting to address in the trial [pharmacokinetics, biodistribution, metabolites, etc.]," he notes. "Accium can tell them what is or is not do-able with AMS."

To optimize its service offerings, Accium is developing relationships with clinical research organizations in the Pacific Northwest. It has a co-promotion arrangement with Radiant Research, a group with access to 50 clinics nationwide and three dedicated 14C trial units. Accium is also working with Northwest Kinetics Inc., which conducts specialized Phase I clinical trials in the vicinity, including trials involving 14C-labeled compounds.

Although preclinical and clinical applications will dominate Accium's business, AMS also has uses in research including development of single-cell assays capable of examining the detailed evolution of pathways (e.g., to determine the uptake of a drug, or how metabolites are taken up in the nucleus or organelles). AMS may also enable systemic, whole-body assessment of biomarkers. "As we grow, we could pursue opportunities in diagnostics and early detection of biomarkers, as well as research collaborations and joint arrangements for the development of diagnostic assays and kits—becoming a central lab in the way that LabCorp. is within the diagnostics industry," Arjomand suggests.

In January 2006, Accium rounded out its management team, naming Glenn Kawasaki as CEO. Kawasaki, part of the founding team at ZymoGenetics Inc. , had reviewed Accium's initial round of financing for lead investor WRF Capital, and he ultimately made a personal investment in the start-up. Arjomand will now focus his activities on technical operations.

Prior to founding Accium, Arjomand was director of technical business development at CombiMatrix Corp. Accium co-founder and VP, business development and sales Michael Chansler, was previously director of international business development at CombiMatrix; he also held various sales positions at Bio-Rad and founded FPMC Inc., a biotech sales consultancy. VP, strategic development Edward Eadeh also worked with Arjomand and Chansler at CombMatrix during his tenure there as VP, sales and business development. Eadeh also had stints as VP, business development at Acuson Corp. and VP, operations at Sterling Medical.—MLR