Phase 1b Multi-Dose Study to Build on Success in Phase 1a

Akebia Therapeutics, Inc., a small molecule discovery and development company focused on anemia and vascular disorders, today announced that it has initiated dosing for a phase 1b multi-dose clinical trial of AKB-6548, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) in development for anemia. The phase 1a study of AKB-6548 demonstrated a dose-related increase in erythropoietin with no significant adverse events.

“We are pleased to be rapidly moving AKB-6548 into phase 1b studies following the successful completion of the phase 1a trial,” said Joseph Gardner, Ph.D., president and chief executive officer of Akebia. “In this next study we will continue to monitor the safety profile of AKB-6548 as well as erythropoietin and other biomarkers in a multi-dose setting. We are excited about the potential of this compound, and that early results have supported our goal of providing patients with a product that offers unique advantages over current approaches to address anemia including simple oral dosing, and an improved safety profile.”

The phase 1b study is designed to evaluate the safety, tolerability and pharmacokinetics of three ascending series of doses of AKB-6548 in healthy volunteers. Volunteers will be dosed with AKB-6548 once daily for ten days. In addition, the efficacy of AKB-6548 will be ascertained by measuring erythropoietin and other biomarker responses including VEGF, hepcidin, transferrin and ferritin. The trial will involve approximately 33 healthy volunteers and will be conducted at Medpace, Inc. in Cincinnati, OH. The study is expected to be completed by mid-2010.

In early January, Akebia announced the successful completion of the first-in-man phase 1a study for AKB-6548 in healthy volunteers. In the clinical study, a single dose of AKB-6548 increased EPO levels and was found to be safe and well tolerated.

About HIF-PH

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in oxygen, or hypoxia, in the cellular environment. HIF-PH’s are the hypoxia inducible factor prolyl hydroxylase enzymes that normally regulate the levels of HIF in bodily tissues. By inhibiting HIF-PH enzymes, HIFs can be stabilized or up regulated, allowing the body to better respond to reduced oxygen, injury and infection. The ability to stabilize HIFs may lead to treatments for many conditions including anemia, fractures, wounds, and other conditions where the HIF mechanism is not functioning optimally.

About AKB-6548

AKB-6548 is an orally bioavailable HIF-PH inhibitor designed to increase natural production of EPO, a glycoprotein hormone that controls red blood cell production. Inadequate EPO production by the kidney is a common cause of anemia. Akebia will initially target patients with chronic renal disease and pre-dialysis patients, two patient populations that are currently undertreated for anemia. AKB-6548 potentially promises to be a safe, cost effective, orally dosed drug that delivers the efficacy of injectable EPO stimulating agents.

Cellectar Inc. has raised $2.7 million for its radiopharmaceutical technology that treats and detects a variety of cancers, according to a Securities and Exchange Commission filing.

Cellectar’s lead compound, called CLR1404, is currently in Phase 1 clinical trials for cancer treatment. In preclinical studies, the molecule has been accepted and retained in 45 types of solid tumors, according to Neal Sandy, Cellectar’s chief operating officer.

The company’s immediate goals center on continuing to progress through clinical trials. Cellectar is not at a point that it needs to decide what type of cancer it is going to target in its first drug commercialization, Sandy said.

Based on its previous fundraising, Cellectar appears to be among Wisconsin’s most promising health care start-ups. The company raised $13 million in early 2008 to fund operations, as well as its Phase 1 trial, Wisconsin Technology News reported.

That round was led by Venture Investors LLC, which has offices in Madison and Ann Arbor, Mich. John Neis, a managing director with Venture Investors who leads the firm’s health care practice, joined Cellectar’s board after the deal. Neis’ voicemail message said he was out of the country and he didn’t immediately return an e-mail.

In 2007, the company raised $7 million, an amount that was called the largest angel round in Wisconsin history.

The company’s radiopharmaceutical technology works by using a radioactive isotope to attach to and kill a cancerous tumor. The drug, which is injected into a patient’s body, doesn’t attach to healthy tissues.

The company’s technology is based on research conducted at the University of Michigan and University of Wisconsin.

The $2.7 million funding comes in the form of debt, options or warrants. The company has no revenue, according to the SEC filing.

Virent Energy Systems, Inc. announced today that it has been awarded $2.4 million from the U.S. Department of Energy as part of a $33.8 million grant to the National Advanced Biofuels Consortium (NABC). The NABC aims to develop technologies to convert cellulosic biomass feedstocks into hydrocarbon fuels that are sustainable, cost-effective, and compatible with existing infrastructure.

The funding will enhance Virent’s on-going efforts to break down cellulosic biomass into sugars that can be further processed into biofuels that are cost-competitive with petroleumbased fuels. Virent’s innovative BioForming® conversion process utilizes both conventional and non-food plant sugars, although fuels made from non-food sugars are not currently cost-competitive. Industry analysts and policymakers believe that promoting technologies to reduce the price of non-food cellulosic feedstocks would be the most effective way to lower the price of the finished fuel and enable these advanced biofuels to achieve broader acceptance and commercialization in the transportation fuel marketplace. Virent currently produces its high octane, energy dense green gasoline using feedstocks as diverse as sugar cane, sugar beets, woody biomass, switchgrass, bagasse, or corn stover.

“Virent is pleased to be the recipient of this grant from the Department of Energy as part of the NABC and we are looking to enhance the competitiveness of cellulosic biomass as a biofuel feedstock because of its considerable potential as a high-impact energy source,” said Lee Edwards, CEO of Virent. “Combining inexpensive sugars from plentiful cellulosic biomass, such as agricultural or forestry residues, with already substantial quantities of conventional sugar feedstocks, could dramatically increase the volume of renewable fuels produced globally without impacting food, feed or export demands,” according to Edwards.

In addition to fuel price, compatibility with today’s petroleum distribution infrastructure would speed market acceptance of biofuels. The most direct way to achieve this is to produce renewable hydrocarbon fuels that match petroleum fuels in molecular composition, energy content, and performance. Virent’s BioForming process generates the broad range of gasoline, jet fuel, and diesel hydrocarbon molecules now refined only from petroleum. Virent’s renewable fuels can be used at high blends with, or as drop-in replacements for, petroleum fuels with no new infrastructure investment.

“Biofuels must be compatible with the nation’s engines, pipelines and refineries to play asubstantial and effective role in reducing carbon emissions and reducing oil imports,” said Dale Gardner, National Renewable Energy Laboratory (NREL) Associate Director for Renewable Fuels and Vehicles. NREL is jointly leading the NABC with the Pacific Northwest National Laboratory.

“The economical conversion of plentiful cellulosic biomass into renewable, fungible hydrocarbon fuels is the most realistic alternative to create a clean energy transportation sector in the coming years,” said Edwards. “Virent has proven it can transform cellulosic, non-food sugars into environmentally superior hydrocarbon fuels with the same composition and performance as petroleum fuels. Progressing biomass deconstruction to provide inexpensive cellulosic sugar feedstocks is the final hurdle to achieving a complete and
sustainable biofuels solution.”

Virent’s work in cellulosic pre-treatment and deconstruction initially began in 2007 with a two million dollar Advanced Technology Program grant from the National Institute of Standards and Technology. The award announced today will specifically fund Virent’s investigations of pretreatment strategies for releasing sugars from biomass and improved catalysts for the conversion of biomass-derived sugars to hydrocarbons as well as the process and engineering design to integrate these improved technologies with Virent’s BioForming process.

ABOUT VIRENT ENERGY SYSTEMS

Virent’s BioForming process is a leading technology for the production of fungible advanced biofuels, including green gasoline, diesel, and jet fuel. The process has won numerous technology and innovation awards including the U.S. Environmental Protection Agency’s Presidential Green Chemistry Challenge and the World Economic Forum’s Technology Pioneer awards. Headquartered in Madison, WI, Virent has 80 employees in a state of the art catalytic biorefining development facility. Virent counts Cargill and Honda among its leading investors and has a collaboration with Royal Dutch Shell to commercialize the production of green gasoline. The BioForming technology is based on the Aqueous Phase Reforming process.

NanoBio Corporation announced today that a sixth U.S. patent covering its novel nanoemulsion technology has been awarded. The patent encompasses composition of matter claims for the company’s lead anti-infective and vaccine product candidates.

“We are very pleased with this patent award in that the new claims circumscribe all of NanoBio’s anti-infective and dermatological products, as well as our intranasal and intramuscular vaccine adjuvants,” said James R. Baker, Jr., MD, NanoBio’s CEO and founder. “The timing of this allowance coincides nicely with several very important development milestones at NanoBio.”

In December 2009, NanoBio and GlaxoSmithKline plc (GSK) announced an exclusive licensing agreement in the United States and Canada for the over-the-counter use of NB-001, NanoBio’s lead product for the treatment of herpes labialis (cold sores). NanoBio is currently preparing to study the efficacy and safety of 0.3% NB-001 in two Phase 3 trials.

In addition, NanoBio’s lead vaccine candidate, NB-1008, a seasonal influenza vaccine administered via a nasal dropper, has shown very promising results in a recently completed Phase 1 clinical study. The company is currently in partnership discussions with several parties regarding NB-1008.

The development of the nanoemulsion platform began in the 1990s at the University of Michigan, and has since been supported by over $110 million in grants, investments and partnership funding. The newly issued patent (U.S. #7,655,252) is licensed from the University of Michigan to NanoBio Corp. on an exclusive, worldwide basis. With this new patent, NanoBio now holds six U.S. patents and has filed over 30 additional applications.

About NanoBio

NanoBio® Corp. is a privately held biopharmaceutical company focused on developing and commercializing dermatological products, anti-infective treatments and intranasal vaccines derived from its patented NanoStat™ technology platform. The company’s lead product candidates are treatments for herpes labialis (cold sores), onychomycosis (nail fungus), acne, cystic fibrosis and a broad platform of intranasal vaccines. The company’s headquarters and laboratory facilities are located in Ann Arbor, Michigan.

A new device to improve in-vitro fertilization uses Braille pins to provide gentle rocking motion to embryos that sit at the bottom of its funnel. Pregnancy rates in mice increased by 22 percent with the use of this device. (Credit: Image courtesy of University of Michigan)

Gently rocking embryos while they grow during in vitro fertilization (IVF) improves pregnancy rates in mice by 22 percent, new University of Michigan research shows. The procedure could one day lead to significantly higher IVF success rates in humans.

Researchers built a device that imitates the motion that embryos experience in the body as they make their way down a mammal’s oviduct (a woman’s Fallopian tube) to the uterus. Currently in IVF, eggs are fertilized with sperm and left to grow for several days in a culture dish that remains still. Then the embryos are transferred to the uterus.

“By making the cells feel more at home, we get better cells, which is key to having better infertility treatment,” said Shu Takayama, an associate professor in the Department of Biomedical Engineering and in macromolecular science and engineering.

Takayama and Gary Smith, associate professor in the Department of Obstetrics and Gynecology at the U-M Medical Center, are co-authors of a paper detailing the findings published online in the journal Human Reproduction.

Their device holds early-stage embryos, which are about half the size of the period at the end of this sentence, in a thimble-sized funnel. The bottom of the funnel is lined with microscopic channels that allow fresh nutrient-rich fluid to flow in and waste products out. The funnel sits on rows of Braille pins that are programmed to pulse up and down, pushing the fluids in and out of the channels.

The current the Braille pins generate simulates flows that occurs in the body due to muscle contractions and the motion of hair-like projections called cilia that line the oviducts. In the body, these motions help to push fertilized eggs to the uterus and flush out eggs’ waste products.

Compared with mouse embryos grown in a static dish, those incubated in the new dynamic device were healthier and more robust after four days. Those grown in static dishes contained an average of 67 cells. Those grown in the new device had an average of 109. Control embryos that had matured in the bodies of mice for the same amount of time had an average of 144 cells.

Approximately 77 percent of the rocked mouse embryos led to ongoing pregnancies, compared with 55 percent of the statically-grown embryos. In a control group of mouse embryos conceived naturally and grown within the oviduct, 83 percent led to ongoing pregnancies.

“One of our goals for years now has been to modify how we grow embryos in the lab to be more like how they grow in the human body, because we know that the human body grows them most efficiently,” Smith said.

Infertility affects one in six couples, Smith said. Many of them turn to IVF, which can cost $15,000 per cycle and is often not covered by insurance. Currently, it has a success rate of about 35 percent.

“If we could increase that, even just to 45 percent, that’s significant,” Smith said. “We’re making healthier embryos, which not only can improve pregnancy rates, but also could allow us to transfer fewer embryos per cycle and reduce the incidence of twins and triplets.”

Through the company Takayama and Smith founded, Incept Biosystems, human clinical trials have begun.

Smith is also an associate professor in the departments of Molecular and Integrative Physiology and Urology, as well as director of the Reproductive Sciences Program.

The paper is called “Dynamic Microfunnel Culture Enhances Embryo Development and Pregnancy Rates.” The research is funded by the National Institutes of Health, the U.S. Department of Agriculture, the Michigan Economic Development Corp., the U.S. Army Research Laboratory and the Coulter Foundation.

This year’s Best of Madison Business Awards honor three organizations and their leaders whose fingertips are all over the social, physical and economic landscape of our growing city.

Successful business people are builders. Whether it’s a company, a product line or a reputation, the best in business—through vision, talent and determination—build. This year, our 2010 Best of Madison Business Award winners are builders in the truest sense of the word, building a foundation for this community’s most important civic assets, building a new employment and economic development sector and building … buildings.

Rich Lynch
J.H. Findorff & Son Inc.

Madison would not look the way it does without J.H. Findorff & Son Inc. For 119 years now Findorff has been constructing the built environment in which many of us live, work, worship and play. The company’s website has pictures of nearly 150 Findorff projects. They ring the Capitol Square, highlighted by Monona Terrace, then stretch out to CUNA Mutual Insurance’s headquarters, The Don & Marilyn Anderson HospiceCare Center, Epic Systems, and back to the UW campus, the zoo, hospitals, schools and churches, and the magnificent Chazen Museum of Art addition going up before our very eyes. And in a meaningful and symbolic commitment to this city,

Findorff rebuilt its own headquarters on the South Bedford and West Wilson site of the company’s offices for the last 100 years, a stunning building that is itself a contribution to the city’s architecture and design. Findorff president and ownership partner Rich Lynch is adamant about crediting the strong leadership team at the helm of the company. But there is no better ambassador than Lynch himself. His personality and generous spirit and love of community are reflected in Findorff’s support for the American Diabetes Association’s “Tour de Cure,” Project Home’s “Hammer with a Heart,” the Construction Careers Initiative and especially United Way, where Lynch takes the helm for the 2010 campaign.

Kathleen Woit
Madison Community Foundation

If Findorff’s buildings are the bricks and mortar foundation of this community, the philanthropic infrastructure has been built by the Madison Community Foundation. From modest beginnings in 1946, MCF today encompasses more than 860 individual funds with assets in excess of $100 million. Donor advised and designated funds meet rigorous standards in support of this community’s most important cultural and civic institutions. Under the leadership (since 1997) of MCF president Kathleen Woit, an experienced and talented staff, and an outstanding board of some of the city’s most prominent leaders, the foundation has earned the trust of those with the means and the interest to invest in Madison’s future. But even more impressive is Woit’s passion and commitment to the Madison of today, nimbly allocating undesignated funds to the community’s most pressing needs. It’s a reflection of her, too. She’s a native, a “homey,” and she wears her love for this city on her sleeve. Healthy communities have a handful of bedrock pillars of support upon which they rely. The Madison Community Foundation is one of those for this community and Woit’s role in building it has won respect, trust and admiration.

John Neis
Venture Investors

Successful building requires innovation. In the context of Madison’s increasingly important and successful biomedical sector, innovation is typically associated with science, research and discovery. But as every start-up and aspiring entrepreneur has learned, innovation is a fundamental need in funding as well. John Neis has been recognized by none less than Forbes as one of the top 100 dealmakers in the world. The managing director of Venture Investors and head of that company’s health care practice, Neis has served on the board of directors of companies from formation to initial public offer or sale, including Virent Energy Systems, Deltanoid Pharmaceuticals, Tomo Therapy and Third Wave Technologies. The governor appointed Neis to the board of the Wisconsin Technology Council and he serves on the advisory board of the University of Wisconsin School of Business. Simply put, the future of greater Madison as a globally recognized and competitive biotechnology center depends on a steady and growing stream of venture capital and angel investments.

Neis is widely respected for his skill, his knowledge and his style. As we considered candidates for this honor we’ll just say he was highly recommended. His contribution to cutting-edge research and science companies was just what Madison Magazine’s late editor Brian Howell had in mind when he drew attention to the importance of innovation in the life sciences and new technology. John Neis is this year’s winner of the Brian D. Howell Award for Excellence in Innovation.

Look around this great city and you’ll see the Findorff cranes dotting the skyline. Look deeper and you’ll see the biotech companies emerging, growing and forming a cluster of economic development. Look deeper yet and find a foundation of philanthropic support and structure that make this city great. Madison is built upon all three.

Neil Heinen is editorial director of Madison Magazine.

Akebia Therapeutics, Inc., a small molecule discovery and development company focused on anemia and vascular disorders, today announced that it has successfully completed the first-in-man phase 1a study for AKB-6548 in healthy volunteers.  AKB-6548 is an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor designed to increase the natural production of erythropoietin (EPO) in anemic patients.  In the clinical study, a single dose of AKB-6548 increased EPO levels and was found to be safe and well tolerated.

“The completion of this phase 1a study is clearly an important milestone for Akebia, and we are very pleased to have human safety data and markers of efficacy in humans,” said Dr. Robert Shalwitz, M.D., chief medical officer of Akebia. “After carefully selecting AKB-6548 from a series of analogs and moving it into human trials it is very gratifying to see the drug perform so well. There were no serious adverse events at any of the doses tested, and the compound produced a robust, dose responsive increase in EPO concentration. Based on the results from this phase 1a trial we look forward to moving AKB-6548 into phase 1b and 2a clinical trials in 2010.”

The phase 1a study involving 48 healthy volunteers was designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic responses to single ascending doses of AKB-6548. The efficacy of AKB-6548 was determined by measuring EPO and other biomarker responses. In particular, doses of AKB-6548 producing significant increases in EPO did not change levels of vascular endothelial growth factor (VEGF). VEGF is a biomarker that potentially is upregulated by HIF stabilization. Separation of the EPO response from a VEGF response is critical for a chronic therapeutic that may be used in patients with anemia associated with either chemotherapy or chronic kidney disease. The Phase 1a trial was conducted at Medpace, Inc. in Cincinnati, Ohio.

About HIF-PH

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in oxygen, or hypoxia, in the cellular environment. HIF-PH’s are the hypoxia-inducible factor prolyl hydroxylase enzymes that normally regulate the levels of HIF in bodily tissues. By inhibiting HIF-PH enzymes, HIFs can be stabilized or up-regulated, allowing the body to better respond to reduced oxygen, injury and infection. The ability to stabilize HIFs may lead to treatments for many conditions including anemia, fractures, wounds, and other conditions where the HIF mechanism is not functioning optimally.

About AKB-6548

AKB-6548 is an orally bioavailable HIF-PH inhibitor designed to increase natural production of EPO, a glycoprotein hormone that controls red blood cell production. Inadequate EPO production by the kidney is a common cause of anemia. Akebia will initially target patients with chronic renal disease and pre-dialysis patients, two patient populations that are currently undertreated for anemia. AKB-6548  potentially promises to be a safe, cost effective, orally dosed drug that delivers the efficacy of injectable EPO stimulating agents.

The market for chronic anemia drugs, which generates over $10 billion in worldwide sales, is dominated by injectable forms of recombinant EPO. There are currently no orally dosed small molecule drugs for the treatment of chronic anemia.

About Akebia Therapeutics

Akebia Therapeutics is a discovery and development company focused on anemia and vascular disorders. Akebia’s lead program, AKB-6548, an orally bioavailable HIF-prolyl hydroxylase (HIF-PH) inhibitor for patients with anemia, is in phase 1 clinical trials. AKB-6548 potentially promises to be a safer, less expensive, orally dosed pharmaceutical to stimulate endogenous EPO production. Additionally, Akebia has a novel HPTPβ inhibitor / Angiopoietin 2 modulator, AKB-9778, for the treatment of vascular leak syndrome and critical limb ischemia which is scheduled to commence phase 1 clinical trials in mid-2010.