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.
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.
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.
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.
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.
MAEGI is a new class of immunotherapy which activates a customizable group of genes for personalized cancer treatment. It can be used as an off the shelf cancer treatment or a highly customized treatment specific to certain cancer types or patients.
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.
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.
While obesity is a growing worldwide epidemic, there are few effective treatments. This technology aims to inhibit a degradation pathway, therefore increasing heat and calorie burn in patients with obesity.
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.
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.
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.
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.
Idiopathic pulmonary fibrosis (IPF) is a deadly chronic lung disease with median survival of 3 years and with a worse prognosis than lung cancer. 6 million people worldwide are affected - 200,000 in North America are affected with 45,000 dying each year. The progressive decline of lung function characterizing it is interspersed with unpredictable disease flares called acute exacerbations of IPF (AE-IPF) that accelerate lung function loss and increase morbidity and mortality. The annual incidence of AE is up to 20% with a mortality ranging from 35-90%, demonstrating the severity of IPF disease progression and the importance for active disease monitoring (ER visits and hospital stays can amount to >$11,500 per case). Current therapeutics are unable to predict how an individual patient will progress and whether they will respond to available interventions. The market size for biomarker chip detection of PIF is ~$3B, underscoring the need for a more robust treatment for PIF.
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.
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.
Our goal is to develop a new cancer drug that is an antibody drug conjugate (ADC). It targets the pi subunit of the Gamma Aminobutyric Acid Receptor (GABRP) that is aberrantly expressed in a broad range of solid tumors. The target was discovered by the Pusztai lab and a provisional patent application has been submitted. We will use the Blavatnik Fund to perform affinity maturation, generate humanized anti-GABRP antibody conjugated to emtansine and assess the anti-tumor activity in vitro and in vivo.
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.
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.
Over 95% of rare disease have no treatment or cure: there are over 7,000 known rare diseases collectively affectiting 30 million Americans. Many of these disease are genetic disorders, in which there can be considerable genetic variation between patients. Current drug development pipeline does not cater to rare mutations, as drug development often takes more than 10 years and over $2B to get a drug to market, making the small patient populations inhibiting. Even if a therapy is developed, genetic variation of the disease means not all patients in the already-small patient population may be able to be treated, limiting their impact and incentive to develop these therapies.
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.
Human Immunodeficiency Virus (HIV) is a deleterious virus that attacks white blood cells (Specifically CD4 T cells) that fight infection, compromising the immune system and it's ability to fight infection. Untreated, HIV reduces the number of CD4 cells (T cells) in the body - the damage to the immune system makes it increasing difficult for the body to fight off infections and other diseases. Eventually, those infected with HIV develop Acquired Immunodeficiency Syndrome (AIDS), where infections or cancers take advantage of a very weak immune system, including infections that could otherwise be adequately defended against. There is no effective cure for HIV; it can only be managed by antiretroviral therapy (ART). Thus, there is a large unmet clinical need for a cure for HIV.
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.
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.
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.
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.
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.
Activating the innate immune system within tumors is a promising new direction in immunotherapy because it can be used against a broad spectrum of tumor subtypes and it ensures that cells throughout the tumor microenvironment become sensitized, resulting in attack and destruction by T cells. RIG-I is a particularly sensitive trigger of innate immune response in tumors, so agonists of this receptor are promising immunotherapy agents. Through a unique class of RIG-I agonists called Stem-Loop RNAs (SLRs), the scientific team is evaluating the efficacy of SLRs as immunotherapy and antiviral agents.
Rarebase Therapeutics is focused on overcoming cancer chemo-resistance. The scientific merits of Rarebase are based on a series of groundbreaking discoveries made by Andrew Xiao’s lab at Yale School Medicine. They have revealed that the increased presence of a novel, critical base in DNA (N6-methyl adenine) is the major culprit for cancers to acquire resistance. The main goal of Rarebase Therapeutics is to identify chemical inhibitors to block the synthesis of this base, thereby overcoming resistance of cancers to standard therapies.
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.
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.
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.
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.
Cysteine protease enzymes are widely used in a range of chemical manufacturing applications. A naturally found amino acid selenocysteine increases activity of cysteine protease enzymes when subsituted for cysteine. Sec-U-Lar is utilizing this property to substitute selenocysteine in cysteine protease enzymes, increasing their activity more than 100-fold.
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.
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.
Platform technology for sample optimization and pain control in minimally invasive devices for regenerative medicine, blood cancer, bone and soft tissue biopsy. Clinically relevant stem cell doses without culture or genetic manipulation, harvested and isolated at the bedside. Working in stealth mode for 2018.
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.
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.
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.
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.
Inflammatory diseases such as autoimmune uveitis, multiple sclerosis and psoriasis are thought to be driven by over expression of cytokines such as IL-17. Therapeutic approaches to repress expression of pro-inflammatory proteins are promising, but miRNAs which stabilize the targeted mRNA can inhibit this process. This technology uses oligonucleotides to block the target sites of the stabilizing miRNAs, thus leading to decreased stability of the target mRNA. Based on novel insights into the biology of a new class of microRNAs, TargetSite Therapeutics is harnessing the power of a differentiated oligonucleotide therapeutic platform in order to target pro-inflammatory cytokines involved in therapeutic areas of distinct need.
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.
Pathogenic fungi are a major public health threat, causing failure of implanted organs and devices, neonatal mortality and much more. Unfortunately, it is difficult to develop specific drugs against these infections because fungal cells are a lot like those in people: we are both eukaryotes that share a similar set of enzymes and pathways. To address this problem, the Pyle lab has specifically targeted the unique RNA metabolism of fungal cells, giving rise to a new generation of nontoxic drugs that are ready for development and implementation. This has received a Blavatnik Award in May 2019.
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.
The shortage of human tissues for surgical applications has driven the market to identify alternatives, including polymeric and biologic materials. Animal tissue, particularly pig, is closing the gap in the critical shortage of human tissue. Current polymeric and conventional biologics exhibit a high degree of complications, in part due to the lack of adequate integration with the surrounding tissues. Sarcio has developed a superior porcine biologic material that addresses the integration deficiencies of polymeric and conventional biologics. Our material is prepared from pigs carrying a single gene knockout resulting in highly integration-competent decellularized tissues. Sarcio’s decellularized tissues are prepared using routine manufacturing methods and are demonstrably superior to conventional polymeric and biological scaffolds. Sarcio’s first planned application will be for hernia repair, a procedure that is performed up to 1 million times annually in the United States.
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.
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.
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.
The Accurate Cell Injection System (ACIS), a new technology for high throughput cell injections. In the world of IVF and cell injection in general, visual input is unreliable. ACIS can provide reliable and real-time confirmation of cell penetration & viability independent of visualization by detecting cell membrane electrical resistance. ACIS is easily integrated into any cell injection system.