Highlights from The Neurotech Investing and Partnering Conference 2010:
Translational Researchers Showcase Innovation
While venture capitalists have been dialing back on potentially risky early stage investments, translational researchers have been marching ahead. Government funding is pushing new discoveries forward, but sometimes the best of these languish in academic labs where companies and more adventurous investors are less likely to discover them. This year the Neurotech Development Foundation (NDF), a new nonprofit founded to promote the advancement of translational neuroscience research, and several institutes at the NIH (including NINDS, NIMH, and NIA) teamed up to find and showcase the most promising work to Neurotech 2010 attendees in Boston on May 20, 2010.
The projects were selected by a steering committee including industry, government and academic representatives. “We received many abstracts from all over the world and were planning to select the top eight to speak in the Translational Partnering and Investing Opportunities session. The committee ended up identifying an additional five of very high caliber so those speakers were also asked participate in other sessions of the conference,” said Casey Lynch President of NDF and Managing Director of NeuroInsights.
Linda Watkins Professor of Psychology and Neuroscience at University of Colorado and co-founder of the start-up Xalud Therapeutics presented in the Pain and Epilepsy session which was chaired by Health Lukatch of Novo Ventures. “We made a personal connection with a number of venture investors and potential partners at the meeting that we wouldn’t have otherwise known. We are developing a novel gene therapy platform which can be used to treat neuropathic pain, multiple sclerosis and ALS among other indications and require $7 million to move it forward.”
Ben Matteo (Eos Neuroscience) and Ed Boyden (MIT) did a tag team presentation discussing fast approaching clinical applications of optogenics. Eos Neuroscience was founded to focus on one aspect of Boyden’s research at MIT, the treatment of retinal disorders. Matteo showed once blinded mice, escaping a water maze after retinal treatment with rhodopsin gene therapy made bipolar cells in the eye depolarize in response to light. Boyden discussed other implantable device applications of the technology where transfection of specific cell types would be combined with an implanted light source to enable neuromodulation (either activation or deactivation of neurons) with previously unknown specificity. At least one audience member was stunned, exclaiming “This is incredible stuff!”
Jill Heemskerk, Program Director of the Office of Translational Research at NINDS/NIH, chaired the Translational Partnering and Investing Opportunities Session, which was held at the end of the second day. She led off by describing a licensing opportunity developed internally at NINDS. “We have a $25 million drug development program at NINDS which operates like a virtual pharma. Our first goal was to find drugs for patients with spinal muscular atrophy (SMA) and then use that process as a model to go after other diseases.” Novel compounds have been identified for SMA which are now available for licensing. The compounds are in preclinical safety testing for progress into clinical trials in August 2011.
Dr. Gabriela Chiosis from Memorial Sloan-Kettering Cancer Center, followed by presenting her work on tau targeted HSP90 inhibitors for Alzheimer’s disease treatment. As implied by her affiliation, her original interest in HSP90 was for cancer research, but she discovered that inhibition of Hsp90 could restore a multitude of damaged signaling networks thought to contribute to AD including alleviation of aberrant phosphorylation and reduction of protein misprocessing and its associated toxicity. The ability of Hsp90 inhibitors to simultaneously affect multiple pathways is a unique and therapeutically attractive feature of targeting this chaperone.
Chiosis went on to discover Hsp90 targeted small molecule inhibitors with efficacy in AD-cellular and animal models. These agents have CNS-permeability and drug-like features and are covered by MSKCC-owned intellectual property. She intends to form a start-up in 2011 to develop these agents as first-in-class disease-modifying therapies to treat AD, other tauopathies and possibly other neurodegenerative disorders like Parkinson’s disease, amyotrophic lateral sclerosis and Huntington’s disease.
Dr. Bruce Bean from Harvard Medical School discussed the applications of his work to disorders caused by neurogenic inflammation, like neuropathic pain, asthma and autoimmune diseases. Neurogenic inflammation, the local release of inflammatory mediators such as neuropeptides from nociceptor sensory neurons, is mediated by depolarization by voltage-gated sodium channels leading to calcium influx and release of vesicles.
Using sodium channel antagonists, such as local anesthetic agents, is one way to reduce neurogenic inflammation. However, these agents are non-selective, causing a block in all sensory and motor nociceptive fibers, and have a relatively short duration of action. Calcium channel antagonists may also be used, however, membrane-impermeant versions of calcium channel antagonists are inactive when applied extracellularly. Bean and colleagues have developed permanently charged sodium and calcium channel antagonists that are able to enter neurons and act intracellularly to reduce excitability.
Miles Cunningham, a staff physician at McLean Hospital, showed off two new drug delivery technologies. The first, the Intracerebral Microinjection Instrument (IMI), utilizes a microcannula that is 10-fold smaller than conventional devices, thus minimizing trauma and allowing very small brain structures to be targeted. The IMI also allows therapeutics to be disseminated in 3-dimensional space using a single penetration of the brain. In addition, the instrument may function as a recording electrode, therefore permitting exquisite targeting accuracy. The IMI is considered a 510K device and human prototypes have successfully been used in porcine simulations of human neurosurgery. In collaboration with an outside manufacturer, the IMI will be ready for market in 2010.
The second technology, the Convection Enhanced Delivery SYStem (CEDSYS), is an improved method for convection enhanced delivery (CED) of chemotherapeutic to patients with intractable brain cancer. "CED" is achieved by continuous injection of therapeutic into the brain under positive pressure for many hours or days. The size of presently-used delivery cannulas (1-3 mm in diameter) results in backflow, or ‘reflux’, of therapeutic along the walls of the catheter and away from the tumor. Also the large size does not permit precise placement. The CEDSYS addresses these problems by utilizing specialized flexible microcannulas that are positioned within the tumor using a computerized guidance system. Thus, the CEDSYS represents a more sophisticated approach to a method that is already being applied to human subjects. It is covered by pending U.S. and foreign patents and will be introduced to the market in 2011.
To date, Cunningham has collected $750,000 from SBIR grants and has started a new company dubbed Atanse to commercialize the two technologies. The company is seeking $1.5 million from strategic partners and/or investors to complete regulatory and intellectual property filings. He plans to license IMI and CEDSYS in next two years.
Dr. Hagit Eldar Finkelman, Professor of Human Molecular Genetics & Biochemistry at Tel Aviv University presented work on substrate competitive GSK-3 inhibitors for neurodegenerative and mood disorders. Recent research has shown that GSK-3 is proapoptotic and regulates axon synaptic plasticity. Overactivity of GSK3 is associated with AD, Parkinson’s, Huntington’s and mood disorders. Lithium is, in fact, a GSK inhibitor.
Most researchers have focused on targeting the ATP binding site which has limited specificity because it is highly conserved between kinases. So Finkelman’s lab focused on substrate competitive inhibitors and, upon screening found a modified 8 amino acid peptide, dubbed L803 that fit the bill. Preclinical results show neuroprotection, axon growth, antidepressive activity, and benefits in type 2 diabetes.
They are now working on structure based drug design to generate a small molecule mimic. Finkelman is interested in discussions with potential collaborations and is considering the formation of a startup.
Ana Lukic, Senior Research Engineer, presented on behalf of Predictek, a company developing software for improved processing of neuroimaging data, dubbed pipelineMAX. pipelineMAX performs automated analyses of PET or fMRI images and Pfizer recently commissioned the company to evaluate regional effects of a CNS drug. Predictek is now forming a new joint venture with Abiant to develop a diagnostic for Alzheimer's disease based on the pipelineMAX technology. So far they believe they can detect “clear linear progression over 5 stages of AD.” They plan to out-license this as a software product.
Mike Vitek, founder and CEO of Cognosci gave a lively presentation of their work on ApoE-based therapies for AD. He pointed out the apparent irony that while only 1% of Alzheimer’s patients have an APP mutation, 99% of the companies are focused on this target. While 45% of Alzheimer’s is thought to be related to the ApoE4 risk factor, and Cognosci is one of only a handful of therapeutic programs based on this target.
Their "COG" compounds are mimetics of ApoE3 which cross the blood brain barrier and appear to provide anti-inflammatory activity, reduce amyloid plaque deposition, and hyper-phosphorylation of tau. The net effect of these combined activities in mouse models of AD is preservation of functioning neurons and improved memory and learning. The company has also demonstrated that COG compounds support enhanced survival of the oligodendrocytes and promote repair of myelin in animal models of multiple sclerosis, nerve crush, and spinal cord injury. The company has been extremely successful in pulling in SBIR funding and is now looking for corporate partnerships to bring the compounds to market.
Lastly, Dr. Junying Yuan Professor of Cell Biology, Harvard Medical School talked about autophagy modulation for treatment of neurodegenerative disorders. Autophagy is a cellular pathway that mediates turnover of vesicles that proteosomes cannot take care of. Too little autophagy and buildup of proteins has been associated with Alzheimer’s, Parkinson’s and Huntington’s while too much autophagy can cause acute neurodegeneration like retinal degeneration.
The Yuan lab developed a number of screens for autophagy modulators and inducers (.2um) as well as inhibitors (30 nm) have now been discovered. Analogs are being optimized for further development. Harvard is interested in collaborations or out-licensing for further development of these compounds.
Justine LaLonde, Business Development Director for CNS at Roche was intrigued by the session. “I was impressed by the quality of the science and the progress made in the academic labs to validate their targets and assess some promising compounds. I spoke with a number of the researchers afterwards and shared their discoveries with key colleagues in Roche. I was glad to be among the first in the industry to take a peek at this research as it can be challenging to source promising academic programs.
Rebecca Farkas, Program Director of the Office of Translational Research at NINDS who was instrumental in working with NDF to pull the session together, said, “I was very pleased with the quality and content of the presentations. Our goal is to increase awareness of the incredible projects our academic and small business grants have been advancing and I think we were able to accomplish that.”
Mark your calendar for The 6th annual Neurotech Investing and Partnering Conference May 25-26, 2011 at the St. Regis San Francisco.
More from July 1, 2010 Issue of Neurotech Insights
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