Aerpio Therapeutics, a clinical?stage biopharmaceutical company focused on advancing innovative therapies for the treatment of diabetic eye disease and inflammatory bowel disease, today announced positive data from its Phase 1 trial of AKB-9778 for the treatment of diabetic macular edema (DME). AKB-9778, a first-in-class human protein tyrosine phosphatase beta (HPTPβ) inhibitor, works to activate Tie2, a receptor on vascular endothelial cells that promotes vascular stability, preventing abnormal blood vessel growth and vascular leak. The data show AKB-9778 was well tolerated through the predicted efficacious dose range, supporting the clinical advancement of AKB-9778.

“Considering the pivotal importance of Tie2 activation in the retinal vasculature, we believe AKB-9778 could offer patients with diabetic macular edema a more effective therapy either alone or in combination with current therapies. AKB-9778 also offers the important benefit of being self-administered, which is not possible with currently marketed treatments,” said Kevin Peters, MD, Chief Scientific Officer and VP of Research and Development, Aerpio. “We look forward to advancing AKB-9778 in the clinic and expect to start a Phase 1b/2a trial in the second quarter of 2012.”

The Phase 1 study was designed to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of AKB-9778 in healthy volunteers. The trial enrolled 48 healthy volunteers and was conducted at Medpace, Inc. in Cincinnati, OH. AKB-9778 was well tolerated through the predicted efficacious dose range with evidence of on-target pharmacology. Together with preclinical data, these findings support advancing AKB-9778 into a pilot 1b/2a study to explore the safety and efficacy of AKB-9778 in patients with diabetic macular edema.

About AKB?9778

AKB?9778 works by inhibiting the Human Protein Tyrosine Phosphatase β (HPTPβ) enzyme, which acts as a negative regulator of the Tie?2 receptor. By inhibiting this negative regulator, Tie?2 signaling is restored, overcoming the effects of the Ang2?induced vascular destabilization. Tie?2 activators have potential utility in a range of important clinical indications, but Aerpio is currently focusing development of its lead candidate, AKB?9778, in diabetic macular edema, with a Phase 1b/2a trial for that indication planned
to start in Q2 2012.

About Diabetic Retinopathy and Diabetic Macular Edema

Diabetic retinopathy, including diabetic macular edema is the leading cause of visual impairment and blindness in the working age population and represents a large and growing medical need that is not adequately addressed by current treatment approaches.

About Aerpio Therapeutics

Aerpio Therapeutics, Inc. is a clinical?stage biopharmaceutical company focused on advancing innovative therapies for the treatment of diabetic eye disease and inflammatory bowel disease. Aerpio is a leader in the development of small molecule drugs based on Tie?2 activation and the stabilization of Hypoxiainducible Factor 1α (HIF?1α). The company’s lead program, AKB?9778, is a first?in?class stabilizer of the Tie?2 pathway and is in clinical development for diabetic macular edema. AKB?4924, a HIF?1α stabilizer, is in late preclinical development for inflammatory bowel disease. More information is available at www.aerpio.com.

Akebia Therapeutics, Inc., a pharmaceutical discovery and development company focused on anemia and vascular disorders, today announced that it has successfully completed a randomized, double-blinded, placebo-controlled Phase 2 dose-ranging study of AKB-6548 in patients with stage 3 and 4 chronic kidney disease (CKD). AKB-6548 is an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor designed to increase the natural production of erythropoietin (EPO) and cause a controlled, gradual rise in hemoglobin in patients with anemia. The study met its primary endpoint of a dose-responsive increase in hemoglobin from baseline over the 42 days of the study (p<0.0001).

"Safe, effective, oral therapies for patients that suffer from anemia associated with chronic kidney disease represents a major unmet need. The results from this Phase 2 study demonstrate AKB-6548's ability to safely and effectively increase hemoglobin levels in a controlled manner, which recapitulates results seen in our prior pilot dose escalation study. We have also identified an optimal dose to take into a larger Phase 2b study, preparations for which are underway,” said Dr. Robert Shalwitz, SVP and Chief Medical Officer of Akebia. “We believe AKB-6548 could offer patients a treatment option that mimics the body's natural response to hypoxia, including erythropoietin production in a highly controllable manner and a well-coordinated iron response. These are key attributes that are unavailable with today's standard of care.”

The Phase 2 randomized, double-blind, placebo-controlled dose range finding study was designed to evaluate the safety, tolerability and pharmacokinetics of AKB-6548 in patients with stage 3 and 4 CKD. Subjects were randomized into 5 different dosing groups, and AKB-6548 was administered orally on an outpatient basis once daily for 42 days. The study enrolled 93 subjects at multiple sites in the United States.

The results show a highly significant, dose-responsive increase in hemoglobin and overall red blood cell production. Specifically:

•On average, patients that received the placebo experienced a small decline, 0.1 g/dL, in hemoglobin by week 6 of treatment
•Patients that received AKB-6548 experienced an increase from baseline to day 42 in hemoglobin, ranging from 0.7 to 1.4 g/dL
In addition, there was a parallel increase in iron mobilization, with significant dose-related reductions in ferritin and hepcidin, as well as an increase in total iron binding capacity (predominantly transferrin).

AKB-6548 was generally well tolerated, with no dose-related changes in adverse events, liver function or renal function as compared to placebo. Of particular note, there were no dose-related changes in vascular endothelial growth factor (VEGF) levels, a HIF responsive gene, at the end of 6 weeks of dosing. Together, these data strongly suggest that AKB-6548 could provide a highly efficacious and well-tolerated oral alternative to currently approved anemia treatments.

About HIF-PH

Hypoxia-inducible factors (HIFs) are transcription factors that regulate the body’s response 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, and causes a controlled rise in hemoglobin levels. Inadequate EPO production by the kidney is a common cause of anemia. Akebia will initially target pre-dialysis patients with chronic kidney disease, a large patient population that is 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 generated over $9 billion in worldwide sales in 2010, is dominated by injectable forms of recombinant EPO. There are currently no approved 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 2 clinical trials. AKB-6548 potentially promises to be a safer, less expensive, orally dosed pharmaceutical to stimulate endogenous EPO production.

Pine tree sugar feedstock was supplied to Virent by Virdia. Photo: Virdia

Biorefining Magazine
By Bryan Sims

Madison, Wis.-based biorefining technology developer Virent Energy Systems Inc. has successfully converted cellulosic pine tree sugar feedstock into drop-in hydrocarbon fuels such as biogasoline and biojet via its BioForming technology platform at its 10,000 gallon per year production facility in Madison. The feedstock was supplied by cellulosic sugar technology developer and provider Virdia, formerly HCL CleanTech.

The joint project is supported by a $900,000 BIRD (Binational Industrial Research and Development) Energy grant, a program for U.S.-Israel joint renewable energy development funded by the U.S. DOE, the Israeli Ministry of National Infrastructures and the BIRD Foundation, which officially launched in January 2011. The grant supported nearly half of the $2.1 million total project cost of the collaborative effort.

According to Randy Cortright, co-founder and chief technology officer of Virent, the project demonstrates Virdia’s novel process technology to deconstruct cellulosic biomass into high-quality sugars and further validates the versatility of its novel BioForming technology to produce hydrocarbon fuels and chemicals from feedstocks other than pure biomass streams. Virent’s BioForming platform utilizes a combination of catalytic processes to convert water-soluble, oxygenated hydrocarbons derived from biomass into nonoxygenated hydrocarbon fuels and biobased chemicals. Virent’s catalysts and reactor systems are similar to those found in today’s oil refineries and petrochemical complexes.

“While Virent’s BioForming process has previously generated fuels and chemicals from sugars in cellulosic biomass,” Cortright explained, “the high-quality sugars generated from pine trees using Virdia’s process leveraged Virent’s conversion process, establishing a viable route to drop-in hydrocarbons from biomass.”

According to Virent, the biojet fuel produced from Virdia’s cellulosic pine tree sugars were sent to the U.S. Air Force Research Laboratory at Wright-Patterson Air Force Base in Ohio for further analysis, where it passed rigorous testing.

“This fuel passed the most stringent specification tests we could throw at it (such as thermal stability) under some conditions where conventional jet fuels would fail,” said Tim Edwards, senior chemical engineer who leads AFRL’s efforts in its fuels branch. “This fuel is definitely worth further evaluation.”

Founded in 2007 as HCL CleanTech originally based in Israel, Virdia has developed a concentrated hydrochloric acid hydrolysis process—trademarked CASE—to convert a range of cellulosic biomass such as wood, energy crops and agricultural residues into high-quality cellulosic sugars and lignin; both of which serve as important feedstocks for biorefining companies.

Since last summer, Virida has been optimizing and refining its sugar conversion process at its pilot-scale cellulose-to-sugar production facility in Danville, Va., on the campus of the Institute for Advanced Learning and Research. The facility is capable of producing about a half a ton of cellulosic sugars per day.

“Passing the Armed Force’s arduous test requirements for jet fuel further substantiates the superior value proposition of the advanced carbohydrates that Virdia is introducing,” commented Philippe Lavielle, CEO of Virdia. “As demonstrated by the BIRD Energy project results, Virdia’s CASE process can deliver the high-purity, cost-effective cellulosic sugars needed as the primary raw material for jet fuels and other applications. We are pleased to work with Virent to prove that the value of cellulosic biomass can be unlocked.”

EB-1020 Is a Norepinephrine and Dopamine-Preferring Triple Reuptake Inhibitor Optimized for ADHD

EB-1020 is Euthymics’ Second Triple, following Amitifadine for Depression

Euthymics Bioscience, Inc. today announced that it has initiated a Phase 1 clinical trial of EB-1020, a next-generation drug in evelopment for treating adult attention deficit hyperactivity disorder (ADHD), with low risk of drug abuse liability. This would meet a critical need because current stimulants used to treat ADHD are tightly regulated and often in short supply due to their addictive properties. Peer-reviewed preclinical data demonstrated that EB-1020 affects areas of the brain associated with ADHD. Dosing of healthy volunteers in the EB-1020 Phase 1 trial is now underway. Final results of the study are expected late this summer.

“Initiating the EB-1020 clinical trial is an important milestone that moves Euthymics from a single drug program to a company with a clinical-stage pipeline,” said Anthony A. McKinney, President and CEO of Euthymics. “Since our formation not quite two years ago we have clinical trials for two separate programs, which speaks to the broad applicability of our science and to the exceptional capability of our team.”

Euthymics develops novel triple reuptake inhibitors optimized for specific indications. Amitifadine, Euthymics’ lead product candidate, is a serotonin-preferring triple reuptake inhibitor being tested as a broad spectrum antidepressant. Amitifadine is being evaluated in TRIADE, an advanced phase 2b/3a clinical trial that is currently enrolling patients at 41 sites in the US. EB-1020 is a norepinephrine and dopamine-preferring triple reuptake inhibitor, with a modest effect on serotonin. This pharmacologic profile modulates the brain chemicals most relevant for the treatment of ADHD with a single molecule.

Frank Bymaster, MS, Euthymics’ Chief Scientific Officer and Co-Founder noted: “I was closely involved in the development of the first non-stimulant for attention deficit disorder—a molecule that acts on norepinephrine pathways to help improve focus. For adult ADHD, I’ve long felt it would help to add a dopamine component that regulates executive function—the person’s ability to organize thoughts and activities, prioritize tasks and manage time. EB-1020 acts on both the norepinephrine and dopamine pathways with the aim of improving focus and executive function (complex problem solving), important components for treating adult ADHD.”

A study presented at the 50th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in December concluded “these data suggest that EB-1020 is a novel agent with improved pharmacotherapy for pediatric and adult ADHD patients, with benign safety, tolerability profiles, and a low incidence of drug abuse liability.” The study was presented by lead author Frank Tarazi, PhD, MBA, of Harvard Medical School and director of the Psychiatric Neuroscience Program at Massachusetts General Hospital, and by Euthymics’ Frank Bymaster.

According to the National Institute of Mental Health, ADHD causes significant impairment in adults, resulting in difficulty functioning, underachievement in school and at work, and poor social and family relations. ADHD affects approximately 10 million adult Americans (about 4 1/2 percent of the population). However, only approximately one in 10 patients is treated, in part due to concerns about administering a potentially addicting stimulant drug to adults.

About Euthymics Bioscience

Euthymics Bioscience, Inc. is a neuroscience-focused clinical-stage company developing next-generation treatments for central nervous system disorders. The company’s lead product candidate amitifadine, currently in a phase 2b/3a clinical trial for depression (TRIADE), is a triple reuptake inhibitor that acts on serotonin, norepinephrine and dopamine in the specific ratio of 1 to 2 to 8, respectively, and is given as monotherapy (a single capsule). Amitifadine has demonstrated proof-of-concept efficacy as treatment for major depression without causing weight gain or loss of sexual function, which often lead to poor adherence to standard antidepressants.

Euthymics is also developing a second triple reuptake inhibitor, EB-1020, to address adult ADHD without the liability of addiction. EB-1020 is a norepinephrine and dopamine-preferring triple in a ratio of 1 to 6 to 14 for norepinephrine, dopamine and serotonin, respectively. It is currently in a Phase 1 clinical trial.

Euthymics is a private corporation with headquarters in Cambridge, Massachusetts. Additional information can be found on the company’s website at www.euthymics.com.

Venture Michigan Fund II announced today that it has made a $15 million investment in Venture Investors Early Stage Fund V, a Madison, WI-based operation with an office in Ann Arbor, MI that focuses on investing in startups spun out of technology from midwestern universities. Venture Investors is expected to make 15 to 18 investments in Michigan companies, each worth between $7.5 million to $12.5 million.

“We are proud to announce this most recent investment commitment to Venture Investors, one of the Midwest’s top firms,” said Sean O’Donnell of the Credit Suisse CFIG Michigan investment office in a press release. (Venture Michigan Fund II is managed by Credit Suisse CFIG.) “The Venture Investors team has a proven track record and we look forward to working with them and sharing in their success.”

Jim Adox, who runs Venture Investors’ Ann Arbor office, says the firm has been operating in Michigan since 2006 and looks for startups with the best commercialization-ready ideas for solving big-market problems. Venture Investors has funded four Michigan companies: Tissue Regeneration Systems, which focuses on medical devices for skeletal reconstruction; HistoSonics, which is developing non-invasive ultrasound treatments for benign prostate disease; NanoBio, which has created a proprietary nanoemulsion for a variety of uses including vaccines and anti-infectives; and Incept Biosystems, which has pioneered a method to improve in-vitro fertilization success rates. All four of the companies are University of Michigan spinoffs.

Adox says that Venture Investors’ Early Stage Fund IV focused primarily on life sciences startups, but the investment trends are shifting, and he expects venture funds to increasingly focus more on the tech and alternative energy sectors. “Life science requires more money and more time,” Adox says. “And also more risk. Everything at the FDA seems subject to change right now. It makes it hard to invest when the regulatory environment is so uncertain.”

Adox says that with wealthy baby boomers getting older and living longer, a lucrative market has been created for things like knee and hip replacements. and ophthalmology treatments to improve vision. Despite that, delays in the FDA approval process have slowed healthcare investment. Adox points out that some of the bigger venture funds have left healthcare investing entirely, with others choosing to work outside the United States—which he sees as a big loss not only to U.S. patients, but to the U.S. economy.

“Typically, the biggest part of a medical device startup’s budget is getting into clinical trials,” Adox says. “If companies choose to do that overseas, that’s money and jobs that won’t happen in the United States.”

Adox says the Midwest provides fertile investing ground thanks to the billons of dollars spent on research each year at its public universities. “Thousands of the world’s brightest researchers are working out of midwestern universities,” Adox says, adding that U-M and the University of Wisconsin are the largest public research universities in the nation. “They’re huge idea-producing engines.”

Inviragen today reported top-line results of a placebo-controlled, randomized Phase 1 trial of INV21, the Company’s highly purified virus particle vaccine against Hand, Foot and Mouth Disease (HFMD) caused by enterovirus 71 (EV71). In the clinical study, healthy adults received two immunizations each of either a high- or low-dose formulation of INV21. Study participants were monitored for safety and for immune response after each administration. Antibodies that neutralize the EV71 virus were measured in individuals who received both doses of the vaccine. One hundred percent of individuals who received the vaccine had significantly increased EV71 immune responses after immunization, which may signify protection against infection. Further, INV21 was safe and well tolerated in this population. Inviragen expects to present complete safety and immunogenicity data at an appropriate infectious disease meeting in 2012.

“Hand, foot and mouth disease is a significant public health problem in East Asia including Singapore. The development of vaccine candidates such as INV21 is a positive result of the strong collaboration between Singapore academic clinicians and local industry partners in addressing emerging infectious diseases threats,” said clinical trial principal investigator Dr. Paul Tambyah. “The results of this first INV21 clinical trial are very promising. We look forward to continued collaboration on HFMD research and carrying out large scale trials in partnership with Inviragen to bring successful vaccine candidates such as INV21 closer to clinical use to help protect vulnerable children in this part of the world.” Dr. Tambyah is associate professor of the Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore and senior consultant, Division of Infectious Diseases at the National University Hospital.

HFMD has taken a significant toll across South East Asia, affecting approximately two million children every year, with severely debilitating and sometimes fatal consequence. Many countries are implementing extra preventative measures in an attempt to control the outbreak. In recent weeks, the number of HFMD cases in Singapore has risen past the epidemic threshold, as defined by the Ministry of Health. In the first nine weeks of 2012, there were 5,568 cases of HFMD, compared to 1,908 during the same period last year. During the first two months of 2012, over 7,700 children in Vietnam contracted HFMD with nine deaths. In 2011, more than 110,000 Vietnamese contracted HFMD and 166 children subsequently died. Malaysia has also seen a recent surge. As of 6 March, the state of Sarawak reported a total of 2,143 cases with 35 pre-school/school and child care centers being served with closure orders in an effort to break the cycle of transmission.

“We were able to initiate this study rapidly and complete it in only six months through a productive relationship with the Singapore National University Health System (NUHS) and our collaboration with Duke-NUS Graduate Medical School,” commented Dr. Joseph Santangelo, Inviragen’s chief operating officer. “Our two-dose INV21 vaccine induced neutralizing antibody responses in all of the immunized adults in this Phase 1 trial and we look forward to exploring the vaccine’s safety and immunogenicity in children in future clinical trials later this year.”

About Hand, Foot and Mouth Disease (HFMD)

HFMD is a disease common in children throughout the world. However, the disease is endemic in the Asia Pacific where its incidence has been increasing steadily over the past two decades. Although the disease is typically of short duration, there has been an increase in severe HFMD infections with sequelae which include neurological symptoms such as meningitis, encephalitis and polio-like paralysis. In 2011 there was an increase in the number of cases of HFMD in East and South East Asia. Recent reports reveal more than two million HFMD infections in 2011. No vaccines or therapeutic modalities currently exist for HFMD.

About Inviragen, Inc.

Inviragen is focused on developing vaccines to protect against infectious diseases worldwide. Inviragen’s vaccine to protect against dengue fever is in Phase 2 clinical testing. A vaccine designed to protect children from hand, foot and mouth disease has completed Phase 1 clinical testing. Vaccines to protect against chikungunya and Japanese encephalitis which affect millions of individuals in Asia, are in development. Vaccines in preclinical research stages include a second generation human papilloma virus vaccine, vaccines to protect against new forms of influenza and a combination plague/smallpox vaccine for biodefense. Inviragen has offices in Colorado, Wisconsin and Singapore. See www.inviragen.com for more details.