Developing Safer Cures for Human Diseases

Modeling Immunity to Enteric Pathogens

One integrated unit with the Mission of developing safer and more effective therapeutics for human diseases

Literature mining & in-house generated data

Creation of the network

Parameter estimation & ODEs adjustments

In silico experimentation Prediction generation

In vivo/vitro validation Hypothesis testing

Refinement of the model with new generated data

SYSTEMS IMMUNOLOGY

APPROACH

Publication!

https://www.nimml.org

Multiscale Modelinghttps://www.nimml.org

> 50,000Mice Utilized

3TBData in Server

> 108Agents in Models

55,419Web Site Visits

$12,000,000Program

> 100/20 Publications/Patents

 > 40Personnel

> 70MMI Participants

> 150Undergrads

https://www.nimml.org

https://www.nimml.org

DRUG DEVELOPMENTI. Identifying / validating new therapeutic targets & biomarkers II. Testing mechanism of action,  PK/PD, efficacy/safetyIII. Human clinical trialsIV. PPARs, NLRs and LANCL2V. Biotherapeutics Inc.

Binding of Abscisic acid & NSC61610 with LANCL2

LANCL2: a new drug target for inflammatory diseases & diabetes. We have Identified a diverse range of NLRs that are significantly 

altered in colons of IBD patients.  Targeting NLR signaling represents a promising and novel therapeutic 

strategy in autoimmune and inflammatory diseases. 

Binding of punicic acid with NLRX1

https://www.nimml.org

NUTRITIONAL IMMUNOLOGYI. Identifying  dietary compounds with anti-inflammatory effectsII. Mechanisms of interaction: diet, microbiome and immune system

PMID:  23541470 

https://www.nimml.org

IMMUNE MEDIATED DISEASESI. Identifying and validating new therapeutic targetsII. Developing computational models of autoimmune disease 

Biologics have limited efficacy and significant side effects.  LANCL2 ligands have demonstrated greater efficacy and no side effects.

https://www.nimml.org

Severity of Disease

5 ASA(MAINT)

Cortico-Steroids

(FLARE UP)

6-MP Immuno suppressant(MAINT)

TNFα (MAINT

FLARE UP)

25 - 40% UC;66 - 75% 

Crohn’s patients require surgery

Drug development

LANCL2 (New Therapeutic Target)

INFECTIOUS DISEASESCombining experimental & computational methods to study the mechanisms of mucosal immunoregulation of H. pylori, E. coli, C. difficile, and influenza virus.

Novel insights on the immunoregulatory mechanisms underlying immune responses to H. pylori infection.

https://www.nimml.org

CHRONIC DISEASESI. Characterizing the mechanisms of action & cell specificity 

underlying the anti-diabetic actions of LANCL2.II. Developing & refining novel animal models of T2D & obesity.III. Investigating the cross-talk between immunity & metabolism.

Guri et al Clinical Nutr (2010) 29: 646-653

AvandiaABA ABA + Avandia

Control

https://www.nimml.org

LANCL2: a new drug target for inflammatory diseases. Initial efficacy of LANCL2 pathway validated in T2D: 

Novel, effective and safe Increased insulin sensitivity through LANCL2 MOA  Results equivalent to prescription Avandia without side effects

COMPUTATIONAL IMMUNOLOGYI. Building multiscale modeling platforms & HPC driven models II. Developing predictive, validated computational models

Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity

Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection

https://www.nimml.org

PMID: 24039925PMID: 25364738PMID: 23592971 

COMPUTATIONAL IMMUNOLOGYI. Building multiscale modeling platforms & HPC driven models II. Developing predictive, validated computational modelsIII. Using computational modeling to accelerate drug development

https://www.nimml.org

https://www.nimml.org

Biotherapeutics Inc. A NIMML/VT Biotech Spin off

The companyFunded in 2008 with the goal of

developing small molecule drugs to treat diabetes and inflammation

Technology PlatformExtensible therapeutic pipeline to treat pathologies based on a unique MoA

Targeted MarketsInitial two markets: the T2D market ($38B) and the IBD market ($8B)

ProductsIdentified several Top Lead Compounds that

are advanced towards IND filing with the FDA. Excellent competitive advantage

Outreach & BDIn discussions with 3 TOP10 Pharma

companies and VC groups. Presence at BIO and JP Morgan Healthcare

conferences

Milestones and FundingClosed seed funding round of over $1.5M. Next round: $5-10M to prepare IND enabling data to

submit to FDA to start human trials

Job CreationThe company is recruiting and contributing to high

quality job creation in Virginia. Employing VT graduates

Developing Safer Therapies from Nature’s Innovations

https://www.nimml.org