Awards Registry

Therapeutic Antibodies for Treating Inflammatory Bowel Disease
Profile last edited on: 3/25/2022

Program
SBIR
Agency
NIH | NIDDK
Total Award Amount
$300,241
Award Phase
1
Principal Investigator
Lauren J Schwimmer
Activity Indicator

Company Information

Abalone Bio Inc

2600 Hilltop Drive Building B Room C332
Richmond, CA 94806
   (510) 288-8776
   N/A
   www.abalonebio.com
Multiple Locations:   
Congressional District:   11
County:   Contra Costa

Phase I

Phase I year
2021
Phase I Amount
$300,241
Abalone Bio will develop antibody (Ab) drugs that inhibit intestinal inflammation to treat inflammatory boweldisease (IBD). IBD comprises chronic, debilitating, idiopathic inflammatory diseases that result in severe dam-age to the gut wall, including Crohn's disease (CD) and ulcerative colitis (UC). The primary etiology is chronicinflammation, which causes pain, diarrhea, weight loss, fever, bleeding ulcers, fistulas, and abscesses in theabdomen and perianal region, and CD patients develop obstructive intestinal fibrosis that must be surgicallyremoved. There is an unmet need for long-acting, broadly applicable disease-modifying, and pain-reliev-ing IBD therapies. There are currently immunomodulators effective as disease-modifying therapies; however,some patients do not respond to them, they have adverse side effects, and their efficacies wane over time. Toaddress this need, we used our proprietary Ab discovery platform to identify first-of-their-kind Ab agonists for aG protein-coupled receptor (GPCR), the cannabinoid receptor CB2. CB2 has immunomodulatory functions inmany diseases that affect several body systems. In humans, CB2 is constitutively expressed in immune cells,and its expression is broadly induced in IBD, including in the colon. Consistently, CB2 function has been firmlylinked to IBD: (1) CB2-KO mice are more susceptible to IBD in disease models, and (2) a common partial loss-of-function CB2 allele has been associated with increased risk of IBD in humans. CB2 agonism has limitedadverse effects, and it can suppress inflammation in the gut and elsewhere, and, in contrast to CB1agonism, it is not psychoactive. Abalone's CB2-specific agonist Abs have many advantages over small-mole-cule CB2 agonist drug candidates, including CNS exclusion and high specificity, which minimize CB1 activation.Furthermore, Abs are natural proteins; thus, they are unlikely to have unexpected adverse effects due to chem-ical by-products. We will test the hypothesis that Abalone's CB2 agonist Abs are feasible pre-clinical IBD thera-peutic candidates with anti-inflammatory effects. Our three major aims are (1) to engineer, produce, and char-acterize CB2 agonist Ab variants based on previously isolated and characterized agonist hits; (2) to eval-uate the anti-inflammatory activity of these CB2 agonist Abs on human immune cells; and (3) to assessthe effects of the top CB2 agonist Abs in two complementary IBD mouse models. Successful completionof this Phase I project will validate this strategy for the treatment of IBD and will pave the way for further devel-opment of these Ab drugs. Although this SBIR application focuses on IBD, Abalone's CB2 agonist Ab drugs areapplicable to other inflammatory, chronic pain, and fibrotic diseases. Compared with small-molecule drugs, bio-logics have an excellent safety record, which supports development and approval for clinical trials and increasedodds of marketing.

Public Health Relevance Statement:
NARRATIVE Inflammatory bowel diseases (IBD) are idiopathic, debilitating disorders caused by chronic intestinal inflamma- tion, and life-disrupting symptoms include pain, diarrhea, weight loss, fever, bleeding ulcers, fistulas, abscesses in the abdomen, and release of blood and mucus. While there are IBD therapeutics, some patients do not re- spond to them, most have adverse side effects, and their efficacies wane over time. In this Phase I project, Abalone Bio will develop innovative and highly specific CB2 antibody agonists that do not cross the blood-brain barrier, making them safer and more effective IBD therapeutics with fewer side effects than small-molecule CB2 agonists currently in clinical trials.

Project Terms:
Abdomen ; Abdominal ; Abscess ; Affect ; Alleles ; Allelomorphs ; Anemia ; Anti-Inflammatory Agents ; Anti-Inflammatories ; Anti-inflammatory ; Antiinflammatories ; Antiinflammatory Agents ; antiinflammatory ; Antibodies ; Antibody Affinity ; antigen antibody affinity ; Antibody Formation ; Ab response ; Antibody Production ; antibody biosynthesis ; immunoglobulin biosynthesis ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biophysics ; biophysical foundation ; biophysical principles ; biophysical sciences ; Blood ; Blood Reticuloendothelial System ; Blood coagulation ; Blood Clotting ; Blood - brain barrier anatomy ; Blood-Brain Barrier ; Hemato-Encephalic Barrier ; bloodbrain barrier ; Cannabinoids ; cannabinergic ; cannabinoidergic ; Cardiovascular system ; Cardiovascular ; Cardiovascular Body System ; Cardiovascular Organ System ; Heart Vascular ; circulatory system ; Cells ; Cell Body ; Chronic Disease ; Chronic Illness ; chronic disorder ; Clinical Trials ; Ulcerative Colitis ; Ulcerated Colitis ; Colon ; Crohn's disease ; Crohn disease ; Crohn's ; Crohn's disorder ; Granulomatous Enteritis ; eleocolitis ; regional enteritis ; Dehydration ; body water dehydration ; Diarrhea ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Engineering ; Eye ; Eyeball ; Fatigue ; Lack of Energy ; Feces ; stool ; Fever ; Pyrexia ; febrile ; febris ; Fissure in Ano ; Anal Fissure ; Anal Ulcer ; Fistula ; Health ; Hemorrhage ; Bleeding ; blood loss ; Human ; Modern Man ; indexing ; Inflammation ; Inflammatory Bowel Diseases ; Inflammatory Bowel Disorder ; Intestinal Obstruction ; Bowel Obstruction ; intestine obstruction ; Intestines ; Intestinal ; bowel ; Liver ; hepatic body system ; hepatic organ system ; macrophage ; Mφ ; Marketing ; Toxic Megacolon ; Mucous body substance ; Mucus ; mucous ; Mus ; Mice ; Mice Mammals ; Murine ; Pain ; Painful ; Patients ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Proteins ; Risk ; Safety ; Salvelinus ; Chars ; Specificity ; Stomach ; gastric ; T-Lymphocyte ; T-Cells ; thymus derived lymphocyte ; Testing ; Time ; Ulcer ; Ulceration ; Vermont ; Body Weight decreased ; Weight Loss ; Weight Reduction ; body weight loss ; wt-loss ; Work ; cytokine ; Sodium Dextran Sulfate ; Interleukin-10 ; CSIF ; CSIF-10 ; Cytokine Synthesis Inhibitory Factor ; IL-10 ; IL10 ; IL10A ; Interleukin 10 Precursor ; Mediating ; GTP-Binding Protein alpha Subunits, Gs ; G(s), alpha Subunit ; G(s), α Subunit ; G(s)alpha ; G(s)α ; GTP-Binding Protein α Subunits, Gs ; Gs alpha Family G-Protein ; Gsα ; Gαs ; Regulatory Ns Protein ; Stimulatory Gs G-Protein ; alpha Subunit Stimulatory GTP-Binding Protein ; alpha-Gs ; α-Gs ; chronic pain ; Malnutrition ; Nutritional Deficiency ; Undernutrition ; dietary deficiency ; malnourished ; nutrition deficiency ; nutrition deficiency disorder ; nutritional deficiency disorder ; base ; Peripheral ; Chronic ; Clinical ; Phase ; Variant ; Variation ; Biological ; Histologic ; Histologically ; Knockout Mice ; KO mice ; Knock-out Mice ; Null Mouse ; CNR2 gene ; CB2 ; CB2 Receptor ; CB2R ; CNR2 ; Cannabinoid Receptor CB2 ; cannabinoid receptor 2 ; cannabinoid receptor type 2 ; Link ; Chemicals ; Liver Fibrosis ; fibrotic liver ; hepatic fibrosis ; Agonist ; Letters ; Therapeutic ; Inflammatory ; Life ; CB1 ; CB1 Receptor ; CB1R ; Cannabinoid Receptor CB1 ; cannabinoid receptor 1 ; cannabinoid receptor type 1 ; CNR1 gene ; Immunes ; Immune ; Organ System ; body system ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; primary sclerosing cholangitis ; experience ; abalone ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Toxicities ; Toxic effect ; Immunomodulation ; immune modulation ; immune regulation ; immunologic reactivity control ; immunomodulatory ; immunoregulatory ; immunoregulation ; Exclusion ; G Protein-Complex Receptor ; G Protein-Coupled Receptor Genes ; GPCR ; G-Protein-Coupled Receptors ; disorder model ; Disease model ; Modeling ; cross reactivity ; Adverse effects ; Skin ; Causality ; causation ; disease causation ; Etiology ; small molecule ; Address ; Symptoms ; in vivo ; in vivo Model ; Antiinflammatory Effect ; anti-inflammatory effect ; Cellular Assay ; cell assay ; Cognitive ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Development ; developmental ; Immunomodulators ; IMiD ; Immune modulatory therapeutic ; immune modulating agents ; immune modulating drug ; immune modulating therapeutics ; immune modulators ; immune modulatory agents ; immune modulatory drugs ; immunomodulating agents ; immunomodulatory agents ; immunomodulatory drugs ; immunomodulatory therapeutics ; pre-clinical ; preclinical ; inflammatory disease of the intestine ; gut inflammation ; inflammatory disorder of the intestine ; intestinal autoinflammation ; intestinal inflammation ; Intestinal Fibrosis ; innovation ; innovate ; innovative ; Therapeutic antibodies ; mouse model ; murine model ; loss of function ; treatment strategy ; drug candidate ; nanobodies ; nanobody ; sdAb ; single domain antibodies ; liver injury ; Injury to Liver ; hepatic damage ; hepatic injury ; liver damage ; liver inflammation ; experimental study ; experiment ; experimental research ; therapeutic candidate ; colon cancer risk ; joint inflammation ; inflamed joint ; joint swelling ; side effect ; blood-brain barrier penetration ; BBB penetration ; bloodbrain barrier penetration ; natural antibodies ;

Phase II

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