SignaBlok, Inc. is a Massachusetts-based biopharmaceutical company developing innovative and first-in-class peptide therapeutics and diagnostics for targeted treatment and diagnostic imaging of a variety of inflammation-associated diseases" through the use of two key SignaBlok's proprietary technologies: 1) novel mechanism-based approach to cell receptor inhibition by using innovative inhibitory peptides (SCHOOL peptides); and 2) multifunctional nanoparticles for targeted delivery of imaging agents and drugs (including SCHOOL peptides) to macrophages. The technologies are based on intellectual property (IP) created by Dr. Alexander Sigalov (eight patents and patent applications) and on related breakthrough science.
SCHOOL PEPTIDE THERAPEUTICS:
Our model of cell signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, enables the rational design of new, receptor-specific inhibitory peptides (SCHOOL peptides) for therapeutic purposes. The SCHOOL peptides employ novel, ligand-independent mechanisms of action and possess unique and beneficial properties. They can be used alone or in combination with other SCHOOL peptides or other therapies. These peptides are non-toxic, non-immunogenic, simple and cheap to manufacture.
CONTRAST AGENTS FOR MAGNETIC RESONANCE IMAGING (MRI):
SignaBlok is using proprietary lipopeptide nanosystems for targeted delivery of the incorporated MRI contrast agents to macrophages (including intraplaque, tumor-associated and synovial macrophages) and other macrophage-type cells that include Kupffer cells and microglia.
We focus on four core therapeutic areas: cancer, atherosclerosis, inflammatory and immune diseases.
ATHEROSCLEROSIS - IMAGING:
SignaBlok's macrophage-targeted imaging nanosystems enable early detection of vulnerable atherosclerotic plaques and risk stratification of vulnerable patients.
Other imaging applications include: 1) diagnostic imaging of early rheumatoid arthritis (RA) and cancer; and 2) assessment and monitoring of drug efficacy.
CANCER, INFLAMMATORY AND IMMUNE DISEASES:
SignaBlok is developing novel mechanism-based first-in-class peptide therapies to suppress the specific inflammatory response mediated by Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1). This approach is known to be beneficial in the treatment of solid tumors, sepsis, RA, atopic dermatitis, atherosclerosis, radiation sickness, retinopathy, and other inflammation-associated diseases.
SignaBlok’s strategy includes the development of nano-based targeted peptide therapies, diagnostics and theranostics for these disorders.
RHEUMATOID ARTHRITIS/Exemplary Use:
Rheumatoid arthritis (RA) affects about 1.5 million Americans and costs society more than $40 billion each year. Despite advances in therapy, RA has no cure. This highlights the unmet clinical need for new treatments. Macrophages are central to the pathophysiology of RA and other autoimmune diseases. Synovial macrophages are the most abundant cell populations found in the synovium of RA patients. Activation of these cells leads to the production of proinflammatory cytokines and mediators.
TREM-1 plays a critical role in the onset and development of RA and represents a highly promising therapeutic target. The true nature of the TREM-1 ligand is not yet known, highly increasing the risk of failure of the current approaches to TREM-1 inhibition in clinical development. SignaBlok developed novel ligand-independent peptide inhibitors of TREM-1 designed by employing the SCHOOL model.
In an animal model of RA, these inhibitors significantly delay arthritis onset, substantially reduce disease severity, and protect against cartilage and bone damage. Targeted delivery of these agents utilizing SignaBlok's self-assembling lipid-peptide nanoparticles significantly increases peptide dosage efficacy.
TREM-1 is involved in other inflammation-associated diseases such as cancer, systemic lupus erythematosus, diabetic retinopathy, atherosclerosis, atopic dermatitis, etc. This strongly suggests that SignaBlok's novel mechanism-based therapeutic compositions can be potentially developed as broad-spectrum anti-inflammation agents for multiple indications.
SignaBlok's TREM-1-targeted SCHOOL concept is proved in animal models of lung and pancreatic cancer, rheumatoid arthritis, atherosclerosis, and sepsis. Other studies in animal models of retinopathy of prematurity and lupus are currently in progress.
Dr. Sigalov has extensive academic and industry experience (over 80 publications in the field). In the 90’s, he founded AMW Biomed Company in Russia. AMW developed and marketed the first diagnostic kits for heart disease and stroke in Russia and was the official supplier of human proteins to DAKO Denmark A/S.
Currently, we are seeking partnerships and collaborations with granting agencies, disease foundations and academia as well as with biopharmaceutical companies and investment organizations to take our products through the IND-enabling studies and clinical trials.
SignaBlok is pre-revenue with $50K "Family and Friends" and over $2M in non-dilutive capital raised up to date. In addition to current NIH grants: $1.34M NHLBI (R44HL110417) and $0.22M NCI (R43CA195684), other government funding includes $0.15M contract W911NF-12-C-0003 from DARPA/DoD and three NIH grants: $0.22M NIAMS (R43AR066376), $0.22M NHLBI (R43HL110417) and $0.22M NCI (R43CA167865).
 Sigalov AB. Int Immunopharmacol. 2014;21:208-19
 Sigalov AB. Contrast Media Mol. Imaging, 2014;9:372-82
 Shen ZT, Zheng S, Gounis MJ, Sigalov AB. PLoS One. 2015;10:e0143453
 Sigalov AB. Innovations Pharmaceutical Technology 2015;54:20-3