Moving Therapeutic Proteins Into the Cytosol and Nucleus. Exolva is using CPMPs (cell-permeant miniature proteins) to deliver therapeutic enzymes and gene-editing tools to correct inborn genetic disease. CPMPs are small, folded proteins that contain a specific array of five Arg residues on an ⍺-helix backbone. CPMPs can reach cytosol and nucleus with efficiencies as high as 75%. CPMPs possess many advantages relative to previous, purported ‘cell-penetrating peptides’, including low toxicity, high and tunable stability, enzyme cargo retains enzymatic activity, among other features.
Understanding the immune response to disease, injury and therapy can have a substantial impact on healthcare. Cellintec will provide a novel, scalable, economic approach using the DNA methylation status of immune cells to derive quantitative, easily standardized immune cell profiles that can be tracked through time and compared between patients and across clinical sites. This capability will enable healthcare providers to choose a cancer treatment based on the level of a patient’s immune suppression, cohort patients for clinical trials based on their immune status, assess an individual’s responsiveness to treatments (especially immune therapies), capture and characterize an autoimmune or allergic response, and monitor a person’s general immune health.
MS patients have an imbalance of Effector and Regulatory cells which causes nerve damage. The solution is a Novel small molecule STAT3 inhibitor, LLL12B, that improves Effector/Regulator cell balance. LLL12b significantly suppresses the disease progression in three murine MS model. There is a great opportunity for this solution as MS is prevalent in 300 people per every 100,000 in the US and is onset in the age range of 20-40.
Dr. KiBum Lee of Rutgers University is developing a nanoscaffold material and system that would enable effective stem cell therapy and drug delivery. The innovation promises functional recovery in patients with central nervous system injuries--like spinal cord injuries--for which there are no effective treatments today. Features of the nanoscaffold include 3D biomimicry, stem cell/neuronal differentiation, ECM-protein binding affinity, efficient drug loading/sustained delivery, and MRI-based monitoring capability.
Foot Drop is a mobility disorder prevalent in patients that is a common result of neurological injuries or diseases such as stroke cerebral palsy, MS or brain tumors. Foot drop is characterized by the inability to lift the toes toward the shin. It inhibits the rhythmic swing phase of the gait, increasing the probability of falls and manifests in abnormal gait patters that inhibit mobility and create imbalances and stress. Currently, there is not a rehabilitative solution that is cost effective and practical for every day independent use. Dr. Tyler Susko has developed a shoe that provides a low-friction out-sole during the swing phase of the gait, and a high-friction out-sole during the stance phase of the gait. The design can be used on any style shoe. Preliminary pilot studies with impaired adults have shown immediate gait improvement.
The current standard for distinguishing between benign and cancerous skin legions require an invasive skin biopsy followed by a waiting period for lab results for diagnosis. OptoVibronix is eliminating the need for invasive skin biopses to diagnose a skin legion as cancerous or benign. The technology scans the skin legion and results in a diagnosis in just 15 minutes. By avoiding skin biospy, it improves the patient experience and efficiency of diagnosis and reduces healthcare costs.
Hemophilia is treated with gene therapy to replace clotting factors. In a large number of patients, the treatment induces inhibitory antibodies which counteract the therapeutic effect. This technology fulfills the need for a treatment for hemophilia and other blood disorders which does not trigger inhibitors. It works by delivering AAV to the liver and producing a therapeutic protein which increases clotting without inducing inhibitors.
Many diseases are managed or treated by invasive IVs or frequent injections. We are all familiar with the difficult routines of chemotherapy to treat cancer and insulin injections to manage diabetes. This is particularly true for diseases that impact the eye. All of us will experience some form of age-related vision loss, with some of the leading causes with no cure shown here, including diabetic retinopathy, glaucoma, and macular degeneration. Loss of vision greatly reduces quality of life, and impacts daily activities we take for granted including reading and driving. Most of these diseases require chronic local treatment to prevent permanent blindness, and the only option may include frequent intraocular injections.
Glioblastoma multiforme (GBM) is an incurable form of brain cancer with no effective therapy. Unlike other organs, brain has limited immune surveillance because of blood brain barrier and lack of lymphatics drainage. Immunaxis proposes to exploit the meningeal lymphatic vessels to overcome immune barrier to achieve successful treatment of glioblastoma.
Triple Target Gene Therapy’s (TTGT's) molecular engineering of adenoviruses allows for the unique pairing of long term gene expression and targeted gene delivery to achieve gene therapy cures. The long term gene expression is achieved via proprietary technology that incorporates CRISPR/Cas. Additionally, the specific gene delivery targeting is accomplished via capsid modification techniques.
Multidrug-resistant Gram-negative bacilli (MDRGNB) have emerged as a challenging cause of hospital-acquired infections and present a critical need for innovative antibacterial development. Two new oxopyrazole agents targeting penicillin binding proteins (PBPs) based on a non-beta-lactam core have superior MIC50 values to current billion-dollar last resort antibiotics like Ceftazidime/Avibactam or Meropenem. One shows broad Gr- efficacy while the second oxopyrazole is selective for Acenitobacter baumannii. On target, good in vivo PK, no mammalian toxicity, no off-target liability. Seeking funding for definitive in vivo efficacy studies.
With combined expertise in MEMS, microfluidics and surface chemistry, Mekonos has created a proprietary cell-engineering platform based on scalable silicon technology for their partners engaged in drug discovery and development. Mekonos aims to sidestep biological genetic engineering processes entirely by using silicon nano-needles to deliver therapeutic payloads directly into the cell in a purely physical, mechanical form factor - with the goals of greatly lowering the cost and time of development, avoiding manufacturing bottlenecks, and perhaps enabling personalized doses to be produced in a hospital setting.
The top 5 drugs sold are delivered by injection, 3 are biologics. Due to discoveries in fields like immuno-oncology, more of these high revenue drugs are biologics. Biologic drugs present a big promise, but they are met with a big problem: They are usually macromolecules, a fact that makes their formulations highly viscous and current injection devices require long injection times and larger gauge needles. The net result for patients is pain and discomfort and therefore reduced acceptance and compliance for treatments. AquaDrive (pka Inviscable) is developing a high performance actuator that could drive formulations 7x more viscous than any other technology currently available on the market, reducing the number of injections by half while minimizing device failure due to the robustness of the actuator at the core of the device.
About half of treated cancer patients receive platinum-based drugs (eg. cisplatin, carboplatin) alone or in co-administration with other anticancer agents. Despite their efficacy, their use is limited by toxic side effects and inherent or acquired resistance to platinum-based drugs by tumor cells. To address this challenge, a Cornell team lead by Prof. Justin Wilson have developed rhenium-based chemotherapeutics for treatment of platinum-resistant cancers.
Novel Therapeutics that Stop Glioblastoma and Other Aggressive Cancers. Sidera's team brings together world-class experts and recognized pioneers in clinical oncology and synthetic biology to discover new targets and small molecules for aggressive cancers. Sidera has identified potent compounds that reduce tumor volume and extend lifespan in rodent models of aggressive human brain cancer. Their innovative platform technologies have spawned partnerships with big pharma to broaden their portfolio and bring them closer to improving patient outcomes.
Our technology combines novelty in bioabsorbable stent technology and regenerative medicine. Our team has unrivaled experience in both technologies and have taken the project funded by the European commission to an advanced stage in development. Our initial therapeutic target will be peripheral vascular disease where there is no comparative technology in use or development. Beyond this, there is potential widespread application of the device and concept to the heart, brain, liver and cancer treatments where the combined technology can provide a unique state of the art therapeutic system.
Artificial Intelligent Medical Imaging: Safer, Faster, Cheaper Medical Imaging Enabled by AI and Deep Learning. The clinical challenges in radiology frequently highlighted are the large radiation doses, long imaging times, expensive hybrid imaging equipment, and expensive room shielding. AI-MI combined with SPECT (Single Photon Emission Computed Tomography) aims to provide equivalent diagnostic accuracy without CT, at lower doses, at lower cost, and faster - allowing for higher throughput through radiology.
Prof. Bob Datta and his team at Harvard Medical School have discovered a new class of odorant receptors - MS4As - that is structurally distinct from previously known receptors. In fact, data suggests that stimulating MS4A-bearing cells can significantly increase food intake in mice by hijacking innate preference mechanisms. The screening platform developed by Bob Datta has the potential to unlock numerous naturally-occurring ligands to create unique additives for food and/or fragrances. The science of the MS4As represents the first truly new opportunity to develop a new class of compounds with the potential to influence human and animal olfactory perception. Sandeep Robert (Bob) Datta is an Associate Professor of Neurobiology at Harvard and he is an entrepreneurial faculty member who is currently working on a number of start-ups.
Dr. Kam Leong from Columbia University’s Department of Biomedical Engineering is developing Cellasphere, a hybrid cell/nanocomposite drug delivery platform that hunts down glioblastoma tumor cells and delivers anti-tumor drugs. Dr. Leong is an internationally renowned leader in the development of nanoscale therapeutics and has pioneered the development of multifunctional nanoscale technologies for delivering drugs, antigens, proteins, siRNA, and DNA to cells. Cellasphere is currently going through the Center for Advancing Innovations, Inc. Brain Race for consideration for a startup.
Loss of brain synapses is highly correlated with symptom progression in Alzheimer’s dementia, but there is currently no treatment to slow or halt synapse loss. Allyx’s prion protein antagonists rescue synapses and memory function by interrupting the deleterious signaling triggered by amyloid without removing plaque itself and are effective at reversing deficits after they develop.
This technology is an antibody-based gene editing method which only requires co-administration of the 3E10 antibody with a donor DNA carrying the edited sequence. 3E10 is a cell-penetrating antibody that binds DNA and transports the donor DNA into cells, where it binds to RAD51 to alter the function of the RAD51 DNA repair pathway to promote gene editing. The antibody/donor DNA combination can be given by IV injection and could be applied to genetic disorders such as sickle cell disease.
Molecular Decisions provides boutique CRO services to pharmaceutical companies, helping them do faster and more confident drug development and clinical trials. The company analyzes clinical or analytical samples using nano-immunoassays that precisely measure specific protein isoform drug targets, enabling sound, immediate decisions related to drug efficacy.
Skin-penetrating catheters and lines, essential to medical management, carry downside risk of superinfection by migration of skin flora. The company is currently working on applying this technology to left ventricular assist devices (LVADs). Of the 2,700 LVADs implanted in 2015, there were 702 infections. There have been efforts to advance the standard of care and use bonded antibacterials, but these interventions have failed to date. The ultraviolet sterilizer transmits a narrow‐band ultraviolet light to a weave of optical fibers surrounding the driveline. Leakage of ultraviolet light will kill microorganisms attempting to migrate down the driveline, thus preventing infection and minimizing cost and toxicity associated with conventional approaches, including long‐term antibiotics and prosthetic device replacement.
PARP inhibitors are promising targeted therapy for cancers with defective homologous recombination (HR) repair. However, as PARP inhibitor become widely used, there will be an increase in patients with PARP inhibitor resistance. To overcome this problem, we have developed DB4, a small molecule drug that inhibits HR repair. Combining DB4 and the PARP inhibitor olaparib inhibits the progression of resistant ovarian cancer and increases the survival time of tumor-bearing mice. Thus, we request the Blavatnik fund to continue developing DB4 for improving its potency and PK properties in vivo and conducting efficacy studies with patient-derived cancer xenograft models in mice.
90% of cancer-related deaths occur due to metastasis. While effective therapies exist to treat primary tumors, treatments to slow/stop metastasis remain ineffective. While immuno-oncology is a new avenue for fighting these metastasized tumors, priming the immune cells has proven difficult. Here, the lab of Prof. King demonstrates a new method to functionalize immune cells. This technology can be applied to metastatic forms of prostate (1.1 million men diagnosed in 2012) and colorectal cancer (1.2 million cases diagnosed in 2015.)
Leptospirosis is the Ebola virus of the bacterial world, difficult to diagnose, and for which there is a 20% mortality rate. Leptospirosis is a global health threat, particularly for travelers and for soldiers. The vaccine for human leptospirosis is unsafe and of unknown efficacy, creating a vast domestic and global demand for an effective vaccine that is currently unmet. Current vaccines are bacterin type vaccines and of limited efficacy, duration, and safety, however LeptoX is offering a first-in-class vaccination (first for animals, to be developed for humans) that outcompetes its competitors in all of these categories.
Approximately 250,000 invasive breast cancer cases were diagnosed in 2019. Currently, the most commonly used definitive way to diagnose breast cancer is through a biopsy. Dr. Anastassiou's team has recently discovered attractor metagene markers as strong prognostic features for breast cancer survival and derived the BCAM (Breast Cancer Attractor Metagenes) prognostic model. This biomarker allows for a single universal prognostic assay applicable to all breast cancer subtypes and stages.
The invention details a new method for producing large quantities of diverse, functional, naïve autologous T cells for infusion into patients. The in vivo generated T cells arise from bone marrow stem cells taken from the patient and become genetically compatible immune cells that are tolerant of the patient and any selected transplant donor. With additional techniques done before collection and transfer, the T cells could also be made to recognize specific targets, altered to resist viruses (e.g. HIV resistance) or directed to become regulatory T cells that may ameliorate autoimmune disease and prevent/treat rejection of transplanted tissues. This technique could address problems such as T-cell exhaustion from cancer patients and the limitations of Ex-vivo expansion of the T-cells.
Kawasaki Disease is an illness that causes inflammation (swelling and redness) in blood vessels throughout the body that comprises three phases, the first of which is usually a lasting fever. The condition most often affects kids younger than 5-8 years years old. Catching Kawasaki disease early is key - children can be treated relatively easily if the disease is detected early, however becomes much more dangerous the longer it goes in diagnosed. The first sign of the disease, fever, is unspecific to Kawasaki disease, and by the time later symptoms manifest, much more aggressive intervention needs to be taken. Thus, a diagnostic that can identify Kawasaki Disease is critical to successfully treating the 5,000-20,000 cases that arise each year in the US, and more globally.
Immuno-Modulators of Alzheimer’s Disease (I.M.A.D.) was founded by Dr. Elizabeth Bradshaw and Dr. Wassim Elyaman from Columbia University’s Department of Neurology. The team is pioneering genetically-driven strategies to treat Alzheimer’s disease by directly targeting susceptibility genes in the CNS innate immune cells, called microglia. Their lead program is a preclinical non-antibody biologic which has been shown to target the CD33 genetic susceptibility signaling pathway in human microglia and clear β-amyloid from the brain of treated mice.
Mucosinix has a new class of antibiotics which have not been shown to trigger resistance in MRSA culture. This new antibiotic class shows promise as a treatment for multidrug resistant microbes.
Non-invasive, accurate diagnosis and monitoring of prostate cancer through diffusion histology imaging. The technique has been validated with patient samples, demonstrates >95% agreement with pathologist-identified tumor stages, and can distinguish protest cancer from prostatitis or benign prostatic hyperplasia.
ARMMs (ARrestin domain-containing protein 1-Mediated Microvesicles) are naturally secreted through an active, protein-mediated process that selectively controls the ARMMs’ cargo and budding mechanism. This system can be easily manipulated to deliver Cas9 and an associated guide RNA for gene therapy or to deliver other therapeutic modalities such as proteins or siRNAs. Additionally, ARRMs are relatively uniform in size, have a low risk of immunogenicity, protect their cargo from degradation, and are predicted to avoid the endosomal pathway for greater efficacy and potency.
We have developed a computational platform for de novo designing of dual inhibitors that can simultaneously engage their targets and (most importantly) augment protein-protein interactions. Employing this strategy and iterative modifications, we have designed and synthesized a mutant selective inhibitor for ALK2, depicting a proof-of-concept for this platform towards the treatment of FOP and DIPG.
Neuro-ICUs are faced with frequent shortcomings in maintaining brain care. Access requires one large or multiple smaller access points and devices require multiple external interface devices & monitors that frequently face challenges in the synchronization, analysis, and interpretation of data. The NeuroProbe System is a portable multimodal implant (EEG, temperature, oxygen, pressure, blood flow) that offers equal or better sensitivity via a single point of access along with synchronized sensor data via a single output connection. NeuroProbe has completed FDA pre-submission and developed prototype NeuroProbe and NeuroMonitor devices, with a system prototype demonstration ongoing in Summer 2019.
Currently available drug-eluting stents release drugs such as sirolimus or everolimus, which stop smooth muscle growth to prevent in-stent restenosis. However, they also block endothelial cell growth and create risk of thrombosis and mandate long-term antiplatelet medication. Nevertheless, yearly, 10% of these stents fail due to late thrombosis or stenosis. We discovered a drug combination (Fas ligand and nitric oxide) which inhibits smooth muscle growth more potently than sirolimus or everolimus but does not affect endothelial growth. This project will lead to the development of a next generation DES with a unique biologically selective effect on smooth muscle and endothelium.
Aging can lead to immunodeficiencies in patients with abnormal thymus function. As a consequence, the body is not able to produce enough new (“naïve”) T cells for the immune system to recognize pathogens and cancer cells or the body is suffering from autoimmune response. Cancer immunotherapy drugs generated $41 Billion globally in 2014, at 50% market share of the overall oncology drugs market . The invention details a new method for producing large quantities of diverse, functional, naïve autologous T cells for infusion into patients. The in vivo generated T cells arise from bone marrow stem cells taken from the patient and become genetically compatible immune cells that are tolerant of the patient and any selected transplant donor.
A vast majority of drugs and biologics fail to enter the brain for treatment of brain cancers and neurological diseases. Our discovery yielded key insights into how the immune system naturally overcomes the blood brain barrier to fight infections. We leverage this insight to enable safe and transient drug access to the CNS using a simple intranasal peptide delivery approach.
Cayuga Biotech aims to develop nanopolyP, a nanoparticle laminated with short chain polyphosphate, for the treatment of acute bleeding. Cayuga's team includes PhD scientists who developed nanopolyP, a regulatory advisor with 23 years of experience at the FDA, and business advisors who have overseen 4 successful biotech exits. Thus far, Cayuga has acquired grant funding to allow significant initial pharmacological and toxicological development. Cayuga aims to build a team, develop a business plan, and complete the few remaining non-clinical studies to file an IND.
Peripheral arterial disease (PAD) is often treated with the placement of unidirectional sheaths into the arteries of patients. These surgeries often require multiple insertion sites, increasing the risk associated with the surgery. This technology is a bidirectional sheath which reduces the number of insertion sites by half, reducing the complications and cost of PAD treatment.
Natural product molecules (and derivatives) are important for the development of modern drugs, as they play a vital role in the pipeline for new therapeutics. For example, >100 FDA-approved drugs are derived from tetracyclic terpenoids, which can be metabolized by the body into steroids. Despite this success, there remain considerable limitations to broad medicinal exploitation of the class due to lingering scientific challenges associated with compound availability. Carbacyclix has developed a concise asymmetric route to forging natural and unnatural (enantiomeric) C19 and C20 tetracyclic terpenoid skeletons suitable to drive medicinal exploration. While efforts have been focused on establishing the chemical science, early investigations reveal that the emerging chemical technology can deliver compositions of matter that are potent and selective agonists of the estrogen receptor beta.
Therapeutics for Fatty Acid Oxidation Disorders. EnergXTherapeutics is developing a platform of drug products that provides comprehensive treatment solutions that targets the biochemical defects induced by deficiency of enzymes/proteins that participates in the mitochondrial long chain fatty acid oxidation (FAO) pathway reactions. Broad IP claims are issued, with more pending, that puts this team in a strong position to utilize its products platform for treating several FAO diseases.
The team has developed a first in class family of molecules that target a membrane receptor present in the most common metastatic brain tumors (breast, colon, melanoma, lung and others), as well as in primary glioblastoma. These molecules are: 1) conjugated to chemotherapeutic agents for tumor-specific intracellular release, 2) cross the blood brain barrier, and 3) designed to work as potential SPECT/PET tracers for tumor detection.
Early indication of fluid accumulation to trigger adjustments to medical therapy preventing costly readmissions and avoiding life threatening complications.
A4 is a novel peptide-based antibiotic that effectively kills multi-drug resistant bacteria, with low propensity to elicit drug resistance. Unlike existing antibiotics or other antimicrobial peptides, the A4-AMP is derived from an antimicrobial protein found in human airways.
There is a growing aging population and there is no cure or treatment for Alzheimer's. The only current drugs are palliative. The Synapse Enhancer enhances the integrity of the synapse which improves cognitive function and can delay/halt neurodegeneration. It could be utilized for a many diseases such as, Alzheimer's, ALS, Parkinson's, Huntington's, Traumatic Brain Injury, Stroke, Epilepsy, Depression, Neuropathic Pain Disorders, and Addiction.
GlimmerX has developed a fast, robust point-of-care diagnostic development platform based on glycoconjugate immunochemistry for common infectious diseases, such as leptospirosis, sepsis, UTI and meningitis that is better than current technologies. To establish proof of principle for our platform, we focus on glycans in leptospirosis, which has a large unmet US and global diagnostics need for veterinary and human disease. In a pilot project, Blavatnik funds would be used for PCT fees, and CRO costs for GLP antigen production, monoclonal antibody production and animal experiments to validate our approach, and they would leverage CT Innovations matching funds and SBIR funding.
Rethinking Adoptive Cell Therapy with Novel Bioprocessing Solutions. InteGRAID’s platform is designed to overcome key cell therapy limitations. This is the first device to recapitulate key T cell signals in an ex vivo lymph node structure for T cell activation. InteGRAID provides paracrine delivery of IL-2, avoiding the issue of T cell exhaustion. And InteGRAID's single-use devices reduce Capex/Opex over the entire product life cycle, reducing risk for cross-contamination and labor costs.
Solid tumors often contain areas of hypoxia or oxygen deficiency. Hypoxia makes tumor cells more aggressive, metastatic and resistant to therapy. Hypoxia is an independent marker of poor patient survival. There are no drugs or effective therapy against hypoxic tumor cells. Hypoxia is the achilles heel' of solid tumors that is common to all solid tumors independent of genetic background. All aggressive late stage tumors are predicted to contain variable fractions of hypoxic tumor cells. Thus, a successful hypoxia-targeting drug has the potential to be used in the treatment of most, if not all, solid tumors. The team has identified a class of antiprotozoandrugs with the ability to kill hypoxic tumor cells - nifurtimox (NFMX) and benznidazole (BZND). NFMX & BZND specifically inhibits clonogenic growth of hypoxic tumor cells with strong selective killing of severely hypoxic tumor cells by inducing lethal damage to the cells' DNA. The team seeks to confirm these findings in vivo and for combination radiotherapy.
Cancers found in dogs often parallel those in humans, and immunotherapies are a powerful strategy to improve quality of life for both patient populations. However, manufacturing canine antibody-based therapies that are non-immunogenic and antigen-specific is challenging. Vetigenics has developed a proprietary canine scFv phage display platform to produce validated antibodies for engineering mAbs, BiTEs, CAR constructsm and other therapies to treat cancers in dogs. A lymphoma targeted therapy will be the first in its veterinary therapeutics pipeline. Vetigenics' platform also provides novel reagents to enable comparative research that can inform and accelerate human drug development. The team is searching for a CEO to develop the strategy, fund-raise, and build a team to bring its validated antibodies to market.