The chair of the session, Steve Mickel, Director of Commercial Development at AbbVie, opened the session with a provocative question; “Can devices pick up where pharmaceuticals leave off?” The landscape is evolving. No longer are we focused on finding one small molecule drug for one disease. Instead, academia, biotechs, and pharma are turning their efforts towards the development of devices and biologics as therapeutic opportunities. Each of the talks in this session appropriately highlighted this shift in thinking, focusing on the use of proteins, peptides, phage, and even devices for the treatment of movement disorders including ALS and Parkinson’s disease.
Dr. RJ Tesi, CEO of FPRT Biosciences, led the session describing his company’s clinical stage protein-based therapy, XPro1595, for the treatment of neurodegenerative diseases including Alzheimer’s diseases, Parkinson’s disease, multiple sclerosis, ALS, and Huntington’s disease. XPro1595 is a blood-brain penetrant anti-inflammatory protein that promotes neuronal survival by treating a single pathology common across many neurodegenerative diseases, excessive neuroinflammation. How does the protein work? XPro1595 is a 17kD “kissing cousin” of soluble TNFα (XPro1595 has six amino acid substitutions as compared to the wild-type protein). The minor changes in sequence gives XPro1595 a therapeutic advantage that in Tesi’s words is “unmatched”; XPro1595 has the ability to selectively bind and neutralize soluble TNFα, while not affecting transmembrane TNFα. XPro1595 sequesters soluble TNFα blocking downstream receptor-ligand interactions that would normally activate an inflammatory response. FPRT Biosciences just closed their Series A financing round and are looking forward to beginning Phase Ia and Phase Ib trials in ALS, which will go through 2015.
In the second talk of the session Jonathan Solomon, CEO of NeuroPhage Pharmaceuticals, spoke about NeuroPhage’s exciting developments using their General Amyloid Interaction Motif (GAIM) technology, which can broadly target misfolded proteins species from oligomers to mature fibrils in protein misfolding diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and ALS. More and more evidence suggests that neurodegenerative diseases share a common underlying pathological mechanism involving the propagation of toxic protein species across the brain via a prion-like mechanism. NeuroPhage’s GAIM technology works to block this propagation via a multipronged approach: 1. targeting multiple pre-existing protein pathologies, including oligomers, and fibers, 2. preventing and blocking the assembly of misfolded proteins, and 3. decreasing the cytotoxicity of misfolded proteins.
NeuroPhage has extensive biochemical and cell-based data to support their GAIM technology, which appears able to robustly target multiple pathogenic protein species in a number of neurodegenerative diseases. Furthermore, NeuroPhage has shown that their approach translates into cognitive behavioral improvements in animal models. NeuroPhage’s original NP002 technology was based on the ability of the filamentous bacteriophage M13 to reduce ß-amyloid in mice. NeuroPhage is currently developing second generation Ig fusion-based product candidates with potentially superior pathogenic protein-targeting properties based on the active motif in NP002.
In the third talk, Winston Ko, CEO of Genervon Biopharmaceuticals, presented data on their “master regulator” therapeutic, GM6, a peptide derived from the naturally occurring protein involved in embryonic development, motoneuronotrophic factor (MNTF). According to Genervon, GM6 has all the advantages of a peptide-based drug: very high potency and activity, low toxicity, minimum drug-to-drug interaction, low accumulation in tissues (i.e., a short half-life), extremely high specificity, and little to no unspecific binding to molecular structures other than the desired targets. GM6 is small enough that it does not have the disadvantages of large peptides in terms of stability, solubility, mutagenicity, immunogenicity, or the high cost of manufacturing through transgenic or recombinant methods.
According to Ko’s presentation, GM6 works through 12 interactive pathways, including axonal transport, RNA metabolism, neuronal plasticity, and protein aggregation. Additionally, GM6 targets 22 biological processes, including neurogenesis, neuronal development, and neuronal signaling. GM6 targets over 80 ALS-related genes, suggesting that GM6 could be an effective therapy in ALS. It looks like we will soon know the answer, as Ko was excited to announce during his presentation that Genervon has recently received FDA approval for testing GM6 in a Phase IIa clinical trial in ALS. Genervon is currently recruiting patients for a Phase II stroke study and a Phase II study in Parkinson’s has also been approved.
In the fourth and final talk, the focus of the session moved from biologics to devices. Geoffrey Thrope, Founder and Managing Director of the venture capital and commercialization firm NDI Medical, spoke about a new technology for deep brain stimulation (DBS) systems developed by a new spinout revealed at the conference, Deep Brain Innovations (DBI). DBI has developed a technology called Temporally Optimized Patterned Stimulation (TOPS) which optimizes the efficiency and enhances the performance DBS systems in Parkinson’s disease patients. TOPS uses an algorithm to identify patterns that can be used to optimize energy and efficiency of DBS devices allowing them to function longer, which in turn minimizes the number of battery replacements required by a device, translating to reduced health care costs and patient risk. A blinded market survey of neurosurgeons showed that TOPS delivers what the market demands.
During the question and answer part of the session, many of the common themes heard throughout the conference were touched on. These included the hesitation that the investment community has around “new” drugs with novel mechanisms, such as FPRT Bio’s TFNα inhibitor and Genervon’s growth factor based drug. Dr. Tesi suggested education is the key to derisking these “new” drugs. At the end of the Q & A, Thrope argued that although the investment community is cautious about investing in “new” drugs, the primary challenge is the limited number of partners willing to invest and the time it will take to see a return on their investment. Although this was somewhat discouraging news, based on the topics discussed in this session, let’s hope the continued successes of these four companies (as well as others) will help to change the way that investors are thinking. - Jessica Goodman