Inferior vena cava (IVC) filters are implantable devices that prevent clots from embolizing from the legs to the lungs. Even though the FDA recommends retrieval of the filter when the risk of VTE or bleeding has resolved, IVC filter removal is technically challenging and sometimes impossible because of tilt and scarring. The team has developed and patented a device that can safely retrieve filters in any configuration.
Therapeutic options for glioma cancers are limited, and the survival rate for glioma patients is poor. Athena is progressing NAMDT inhibitor therapy by applying it to cancers with specific mutations, thus increasing the efficiency and decreasing toxicity of treatment.
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.
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.
Getting immediate medical attention is critical after a patient has experienced a stroke. However, stroke symptoms are often not identified by the patient or family members until it is too late to administer treatment. There is currently no wearable-linked mobile app which specifically detects a stroke incident. AlvaHealth is pairing wearable devices with machine learning to detect a stroke incident immediately based on the activity in both arms of the patient. Early detection of stroke can improve the outlook for patient recovery.
MODA Pharmaceuticals has developed a highly innovative small molecule-based platform for targeting and removing proteins associated with disease. Unlike other targeted protein technologies, which focus on elimination of intracellular proteins via the ubiquitin-proteasome pathway, our technology is the first of its kind capable of eliminating extracellular proteins. MODA small molecules are highly versatile and have the ability to address a broad spectrum of diseases and enhance our understanding of the mechanisms behind human health and disease.
My Gene Counsel has created scalable, digital technology that pairs specific genetic test results with accurate, continuously updating information for clinicians and consumers. By helping patients and doctors become aware of the implications of genetic testing results, My Gene Counsel can help improve patients' lives and avoid unnecessary risky medical procedures.
ProteoWise was founded by a seasoned team of scientists from the Strittmatter Laboratory at Yale University which has a history of commercialization of innovations emerging from the lab. ProteoWise aims to unlock the protein world. Its technology will disrupt the protein analysis industry by enabling researchers to move beyond the current Western Blot standard and into easy, high-throughput bench-top proteomics.
Peritoneal carcinomatosis is a late stage manifestation of colon and ovarian cancer with a poor prognosis. Intraperitoneal (IP) chemotherapy is effective, but current methods lead to toxicity, which is not easily tolerated by patients. We propose a new approach, in which the chemotherapy drug is encapsulated in bioadhesive nanoparticles (BNPs) that can be delivered locally by established IP infusion methods. These BNPs are retained for many days in the IP space, and slowly release chemotherapy drugs, maximizing effectiveness, while minimizing toxicity.
Therapeutic interventions for Angioimminoblastic T cell lymphoma have limited efficacy. TKine Therapies has identified a promising target CXCR5 which is involved in metastasis and found on the cell surface in T cell lymphomas. They have developed a small molecule inhibitor of CXCR5 which is potent at nanomolar concentrations in vitro and which has demonstrated activity in a mouse model of CXCR5-expressing T cell lymphoma.
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.
The Blue Vertical-Cavity Surface-Emitting Laser (BlueVCSEL) is a breakthrough for projection, display technology, & lighting. Overcoming previous obstacles to commercialization, the team has utilized patented techniques to create the world's first stacking-fault-free semi-polar GaN-on-sapphire materials to make Blue VCSELs a commercial reality.
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.
Pattern Therapeutics is a developing a novel TLR (toll-like receptor) antagonist to treat NASH (non-alcoholic steatohepatitis) and potentially other indications. NASH is the most common liver disease in the United States, with an estimated prevalence of 4-6% and predicted prevalence growth of 15-50% in the next 15 years. A critical finding is that TLRs mediate the Sterile Inflammation (SI) response and exacerbates metabolic stress. The candidate antagonist - PT-7314 - is a novel compound with excellent Phase 1 safety data, and strong in vitro and in vivo efficacy in mouse models of NASH. Pattern Therapeutics is ready for Phase 2 trails and is looking for an entrepreneur to raise funds to file an IND, manufacture the drug for the clinic, and to lead the trial.
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.
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.
EliV5 is leveraging their discovery of first-in-class inhibitors of Aspergillus fumigatus pantothenate kinase (PanK), which plays a key role in fungal metabolism and survival, to identify novel, selective and potent drugs to treat aspergillosis and other clinically important fungal infections.
A Novel Platform to Develop piRNA-Based Therapeutics for Cancer Treatment. PIWI-interacting RNAs (piRNAs) is a novel pathway for nucleic acid based targeted therapy. piRNAs consist of small non-coding RNAs that interact with PIWI proteins. The PIWI/piRNA pathway protects the genome from destabilizing transposon activity by using piRNA to guide PIWI proteins to transposable genome sites, leading to gene specific methylation in somatic cells. piRNAs offer potential advantages because the longer piRNA seed sequences results in higher target specificity, higher tissue specificity, higher efficacy, and lower toxicity over siRNA and miRNA techniques. Short-term focus is currently on treating liver cancer because of the relative ease of drug delivery and lack of effective treatments.
Vimentin and Keratin Targeted Therapies for Treating Dermatologic Cancers. The Bunick lab discovered a new mechanism governing proper intermediate filament assembly. We believe topical application of peptide therapeutics can disrupt this mechanism in skin cancer cells, leading to an effective first-in-class anti-cancer therapy.
We have developed a novel linker technology that can enable potent targeting of nanomedicines for therapeutic and diagnostic applications. We further have a unique clinical pipeline for development of this technology using ex vivo perfusion of non-transplanted human organs. Our primary lab, the Tietjen lab, has developed a robust pipeline for preclinical research on human kidney and liver with the capacity to expand to heart and lung in the future. This provides a direct path to clinical impact in organ transplantation and will enable broad translation for a variety of indications.
Our data shows via genetic and pharmacological studies that the Ire1alpha-XBP1 pathway is a novel genetic interactor of Pkd1 and can strongly modulate the progression of ADPKD in murine models by protecting Pkd1 kidney cyst cells from apoptosis without impacting their proliferation. Tilting the balance from low to high apoptosis levels (via inactivation of XBP1 on a Pkd1 KO background) given similar proliferation profiles may thus provide a viable therapeutic option in the context of cystic kidney disease. Given that the target pathway in this case is very well characterized and not needed for kidney development or homeostasis, our data offers a potentially exciting therapeutic option for slowing down ADPKD (and possibly ARPKD) by targeting Ire1alpha-XBP1. Furthermore, we have identified a potent agent that leads to a dramatic decrease in polycystic kidney disease progression in both early and adult mouse models. This agent represents a promising candidate for further pre-clinical/clinical development.
A Novel Chemical Approach to Target p53 Mutation in Human Cancer. There is currently no treatment that specifically targets p53 mutation, the most common genetic abnormality associated with cancer. Loss of p53 tumor suppressor function provides cells with a proliferative advantage but renders them susceptible to metabolic stress. We have developed potent and selective inhibitors for PIP4K2A and PIP4K2B that regulate cell metabolism and are essential for the growth of p53-deficient tumor.
Idiopathic Pulmonary Fibrosis (IPF) is a highly lethal, orphan lung disease with limited treatment options. Vittix Therapeutics, led by Dr. Naftali Kaminski, Chief of the Pulmonary Section at Yale University, has identified thyroid hormone small molecule mimetics as a novel therapeutic approach, targeting mitochondrial function in lung epithelial cells and to date, has produced compelling in vivo proofs of concept. Received a Blavatnik Award in May 2019.
A Natural Nanoparticle Platform for Drug Delivery to the Brain. Drug delivery to the brain is major challenge because of the existence of the blood brain barrier (BBB). Here we present a novel natural nanoparticle platform that can overcome the BBB and enable efficient drug delivery to the brain. We demonstrate a lead product that is readily translated into clinical applications for effective stroke treatment.
Wolfram Syndrome is an orphan disease that has no treatment. Wolfram Syndrome is caused by mutations in wolframin, a protein that is necessary for normal function in cells, by binding to and preventing cleavage of neuronal calcium sensor 1 (NCS1). Center Pharm's drug candidate targets the cleavage site of NCS1. The drug will stabilize NCS1 levels and maintain normal cell functions to delay disease progression.
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.
EPO-VG are implantable grafts composed of cells which release a steady dose of erythropoietin (EPO) to patients with end stage renal disease. These grafts reduce the cardiovascular risks associated with single dose EPO injections, improving cost and patient outcomes.
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.
We have applied a unique, robust, and comprehensive image-based assay developed in our laboratory to discover small molecule inhibitors of nucleolar function. Results from pilot screens on FDA-approved drugs reveal 83 unique hits that include known and putative antineoplastic agents.
Cancer drug efficacy is limited by dosage restructions based on side effects of cancer drugs on healthy cells. Targeting drugs to tumors specifically can substantially improve the efficacy of existing drugs, and reduce the unpleasant side effects of cancer treatment. Cytosolix is using the high acidity characteristic of tumors to preferentially target drugs to these cells. The platform is applicable to 95% of cancers and 90% of those therapies, giving Cytosolix the opportunity to revolutionize drug design in oncology.
The three members of the endocrine FGF family, FGF19, FGF21 and FGF23 are important circulating hormones that regulate a variety of critical metabolic processes. Endocrine FGFs mediate their cellular processes by binding to and activating FGF-receptors (FGFR) in complex with Klotho proteins. Based on the crystal structure of ligand occupied Beta-Klotho new potent engineered endocrine molecules were developed for treatment of metabolic disease that will benefit from therapeutic stimulation of FGF21 cellular pathway such as pancreatitis, Nash and obesity. Moreover, also potent inhibitors including small molecules will be developed for treatment of bone disorders (XLH) and liver cancer, respectively.
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.
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.
Existing brain perfusion systems are focused on preserving immediately harvested organs until transplantation. These systems are not applicable to research and development applications where the organs may not be immediately obtained postmortem. OrganEx has developed an effective method to salvage organs ex-vivo to advance clinical research and transplantation studies.
Pearl Bio is an early-stage venture pioneering design and production of next-generation therapeutics and biomaterials for medical applications and beyond. Biology is constrained to the 20 natural amino acids, limiting the ability to site-specifically modify therapeutic proteins to improve half-life, tissue targeting, or assembly. In contrast, chemical synthesis of therapeutics enables access to greater functional diversity, but template-directed synthesis is challenging. Pearl Bio unites the precision of biology with the unlimited diversity of chemistry in a transformative platform that produces therapeutics and biomaterials with tunable properties for applications in oncology, immunology, and rare disease.
Macrophage Migration Inhibitory Factor (MIF) plays a key role in inflammatory disease and cancer, being an important regulator of the innate immune response. MIF is an inflammatory cytokine; when bacterial antigens are present, it binds to CD74 on other immune cells to trigger an acute immune response. MIF regulates cell proliferation by binding to receptor CD74 in MAPK (ERK) and AKT signal pathways. It also inhibits apoptosis of cancer and inflamed cells by blocking p53, making it an attractive drug target for cancer therapies.
Numerous clinical trials in amyloidosis have failed as a result of misdirected focus on amyloid states of disease-causing proteins. Pangolin Therapeutics’ (PTx) small-molecule platform, termed Pangomers™, was developed to address this deficiency. The Pangomer™ core structure enables selective targeting of pre-amyloid, toxic oligomers (PAOs). Here, we seek to address Multiple System Atrophy (MSA), an aggressive, orphan-indicated form of Parkinson's for which there are no approved therapeutics. Our pilot efforts have identified and validated a strategy for development of Pangomer™ analogues that neutralize PAOs from MSA. Additional funding will allow execution of this strategy delivering a lead molecule for pre-clinical advancement.
Aero Therapeutics is helping physicians in low-resource settings treat neonatal respiratory issues with their sustainable, rugged and affordable devices. Their current device oxygenates, warms, humidifies, and sterilizes air before it is delivered in a single, compact, and mobile enclosure. Developed iteratively in Ethiopia, their final prototype demonstrates comparable performance with commercially available devices at ~1/10th the cost.
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.
Alzheimer's Disease (AD) is a progressive, degenerative disease that is the most common cause of dementia. Brain cell connections and the cells themselves to degenerate and die, eventually destroying memory and other important mental functions. No cure exists, but medications and management strategies may temporarily improve symptoms. An estimated 5.7 million Americans are living with AD in 2018, projected to be 13.8 million by 2050.
Modulation of MAP Kinase Phosphatases in Targeting Liver Disease. A novel platform for allosteric targeting of MAP kinase phosphatases to achieve nodal regulation of signaling pathways that can be leveraged for therapeutic purposes.
Patients who undergo life-saving cardiac procedures (such as aortic valve replacement) are often exposed to a related harm: stroke, infarction, and brain injury. These strokes are due to the release of emboli, or particulate material such as a plaque, that travel in the blood from the heart to the brain during surgery. In response to a growing body of evidence of this problem, Lifeguard is a neuro-protective device that provides coverage to all three aortic arch takeoffs. Lifeguard is led by Yale Professor of Medicine Dr. Alexandra Lansky and Yale Associate Professor of Biomedical Engineering Dr. Tarek Fahmy.
Hypnos is developing an in-ear, wearable EEG and ECG that is non-obstructive, discreet, and attractive to any user who wears earphones and would like to concurrently have real-time brain activity monitoring and feedback of measured variables to improve their cognitive performance and overall well-being. Audience choice winner for the Rothberg Catalyzer Prize at Yale.
"Cold" tumor cancers, such as breast, pancreatic and prostate cancers, are difficult to treat with immunotherapy due to a lack of infiltration into the tumor by T cells. EvolveImmune has developed a treatment which can be used alone or in combination with other cancer drugs to increase the immune response and T cell infiltration in the tumor tissue.
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.
Stenting is frequently used in Peripheral Artery Disease (PAD) to treat the symptoms of Atherosclerosis. However, this treatment has risks, including restenosis 60% of the time and late thrombosis that result in high re-intervention rates, non-healing ulcers, and higher risk for amputation. NuStent is developing an imageable, magnetic biodegradable intravascular scaffold as a new alternative to classical stents for PAD. In vivo porcine studies demonstrated safety and feasibility for deployment.
1 in 400 Americans carry a breast cancer gene (BRCA) mutation - such a mutation increases the likelihood of developing breast cancer from 12 to ~70% by age 80, and raises the lifetime risk of ovarian cancer from 1.3% to 44% (BRCA1) or 17% (BRCA2). Additionally, men with BRCA1 or BRCA2 mutations are also at increased risk for breast and prostrate cancers, and both men and women with either mutation are at an increased risk of pancreatic cancer. BRCA proteins are essential for DNA repair, making BRCA-deficient cells (i.e. those with a BRCA mutation) susceptible to synthetic lethality and providing an opportunity to kill cancers with the mutation. PARP-inhibitors invoke synthetic lethality to kill BRCA-mutated cells via PARP-trapped lesions, however cells can become resistant to this mode of therapy, creating an unmet clinical need for these cancers. Indeed, nearly 300,000 new cases of breast or ovarian cancer will be diagnosed in 2019, making the need for an improved synthetic lethality agent urgent.
Age-related macular degeneration (AMD) is a leading cause of blindness, affecting more than 8 million individuals in the United States alone. Although nutritional supplements are recommended for patients with intermediate risk or advanced AMD, there is still no effective therapy for the 90% of AMD patients with the “dry” or atrophic form. The team at Opti-Peutics used a high-throughput screen to identify novel compounds that protect RPE cells from oxidative damage.
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.
Despite it being a rare disease, pulmonary arterial hypertension (PAH) is a costly and deadly condition of the pulmonary artery. Verso therapeutics is pursuing an HDAC inhibitor as a treatment for PAH which restores normal pulmonary vasculature unlike existing treatments which fail to address the abnormal architecture.