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.
Investor: khosla ventures. 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.
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.
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.
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.
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.
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.
Stradefy Biosciences is developing innovative bioadhesive nanoparticles (BNPs) to deliver therapeutic agents to target tissues at maximally effective doses while reducing systemic toxicities. The Company licensed from Yale technology from the laboratories of Professors Mark Saltzman and Dr. Michael Girardi with high value applications in oncology, autoimmune diseases, and other indications. ESV’s Venture Partner, Brian Dixon, is CEO. Elm Street Ventures led the 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.
(Highcape Capital presented a profile Jan 2022) 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.
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.
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. (Update) Alva Health was part of MassMEDIC's IGNITE 2021 cohort and also participated in the MassMEDIC Startup Stadium during BIOMEDevice Boston 2021. Alva Health is the recipient of the $350,000 grand prize as the winner of its 2021 MedTech Global Competition.
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.
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.
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.
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.