Therapeutic antibodies for treating inflammatory bowel disease

Ended Project Grant Awarded Last action

Award ID
R43DK127654
Recipient
Awarding agency
Obligated
$900,723

Award facts

Completion date
Originally
Funding
  • $600,482.00 Federal
  • $300,241.00 Non-federal
Place of performance
San Pablo, CA, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Abalone BIO will develop antibody (AB) drugs that inhibit intestinal inflammation to treat inflammatory bowel disease (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 chronic inflammation, which causes pain, diarrhea, weight loss, fever, bleeding ulcers, fistulas, and abscesses in the abdomen and perianal region, and CD patients develop obstructive intestinal fibrosis that must be surgically removed. 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. To address this need, we used our proprietary AB discovery platform to identify first-of-their-kind AB agonists for a g protein-coupled receptor (gpcr), the cannabinoid receptor CB2. CB2 has immunomodulatory functions in many 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 firmly linked 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 limited adverse effects, and IT can suppress inflammation in the GUT and elsewhere, and, in contrast to CB1 agonism, 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 assess the effects of the top CB2 agonist ABS in two complementary IBD mouse models. Successful completion of 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 are applicable 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 increased odds of marketing.

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $300,241 $0
Original award $300,241 $300,241

Quick answers

Who received award R43DK127654?

R43DK127654 was awarded to Abalone Bio, Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on May 1, 2021.

How much is award R43DK127654 worth?

$900,723 has been obligated on R43DK127654: $600,482 in federal funding and $300,241 in non-federal funding.

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