Resistant Infectious Disease Technologies
The University of Chicago

Available for download at
tech.uchicago.edu/areas
UChicago’s Unique Infectious Disease Capabilities
UChicago’s unique access to infectious disease facilities, clinical rese...
UChicago’s Multi-front Assault on Infectious Diseases
World-class labs focused on MRSA eradication, along with a marriage ...
Resistance-evading small molecule anti-infectives
New therapeutics have little value if
pathogens rapidly acquire resistan...
Antibody therapeutics and vaccines
UChicago antibodies directly target the
repertoire of pathogen immune-evasion
mechanism...
Subunit and Live Vaccines
Superantigens, toxins, immune system
modulators, clotting factors, and proteins
involved in absc...
Platform Technologies
Novel UChicago platforms allow a consistent
approach to be used against a variety of
pathogens and d...
Available Technologies
Resistance-evading small molecule anti-infectives
UCHI 2215
Daum

Antibiotic potentiator of oxacill...
Available Technologies
Live attenuated strain vaccines
UCHI 2137
Live attenuated S. aureus strains
Schneewind

Optimizing ...
How to Partner with the University of Chicago
Contact UChicagoTech, the Center for Technology Development & Ventures,
to l...
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Infectious Disease Discoveries, University of Chicago

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Infectious Disease Discoveries, University of Chicago

  1. 1. Resistant Infectious Disease Technologies The University of Chicago Available for download at tech.uchicago.edu/areas
  2. 2. UChicago’s Unique Infectious Disease Capabilities UChicago’s unique access to infectious disease facilities, clinical research centers, and world-renowned leaders in the fight against pathogens ensures maximum investment return for industry collaborators. MRSA Research Center Howard T. Ricketts Laboratory (HTRL) • UChicago’s HTRL located at Argonne National Laboratory is one of 13 regional BSL-3 facilities in the US • HTRL mission is the creation of novel therapeutics for biodefense and emerging infectious diseases. Great Lakes Regional Center of Excellence (GLRCE) • MRSA Research Center is a consortium of 20 members at UChicago who collaborate on studying the spread and progression of MRSA disease • Center’s MRSA strain bank receives patient-derived MRSA strains daily from the UChicago Medical Center, stores them and warehouses molecular/clinical info from these isolates • Info used for resistant-resilient antibiotic and vaccine efforts • GLRCE combines the research excellence of inter-disciplinary scientists at 27 member institutions in the Great Lakes region • Biodefense & emerging disease vaccine/therapeutic focus • Administered by UChicago Olaf Schneewind, MD, PhD • Olaf Schneewind is the director of the GLRCE for Biodefense and Emerging Infectious Diseases Research • Dr. Schneewind is a pioneer in using a reverse vaccinology approach to identify key antigens for vaccines that have been show to confer protective immunity in mouse models • “This finding represents a promising step toward identifying potential components to combine into a vaccine designed for people at high risk of invasive S. aureus infection,” Anthony S. Fauci, M.D., NIAID director (NIH News) Robert Daum, MD • Robert Daum is the director of the MRSA Research Center and has been at the forefront of the discovery and raising the alarm about community-acquired MRSA • A Nature news feature “Man vs. MRSA” highlights Dr. Daum’s efforts and the groundbreaking work being done at UChicago on attacking resistance mechanisms • http://www.nature.com/news/vaccine-development-man-vs-mrsa-1.9940
  3. 3. UChicago’s Multi-front Assault on Infectious Diseases World-class labs focused on MRSA eradication, along with a marriage of biochemical and clinical expertise, have lead to a range of technologies targeted to some of the deadliest pathogens. Antibody-based therapeutics and vaccines Resistance-Evading Small Molecule Anti-Infectives MRSA MRSA MRSA X ADAM10 S. aureus (MRSA) MRSA S. pneumoniae Gram positives Anthrax/Bioweapons Toxoplasma Flu Platform Technologies Subunit and Live Vaccines -Peptide Vaccine/Adjuvant Platform -Microbiome-Disease Platform
  4. 4. Resistance-evading small molecule anti-infectives New therapeutics have little value if pathogens rapidly acquire resistance. UChicago’s in-development small molecule anti-infectives avoid resistance by directly targeting resistance pathways, host functions, or conserved and essential cell surface proteins. Without anti-infective With anti-infective MRSA MRSA ADAM10 ADAM10 X ADAM10 Epithelial permeability Representative Technologies Robert Daum, MD • New antibiotics and small molecule potentiators of antibiotic sensitivity for overcoming resistance to therapy in patients with MRSA • S. aureus vaccine development Julie Bubeck Wardenburg, MD, PhD • Topically administered small molecule inhibitor of ADAM10, a host cell surface receptor, for the treatment of S. aureus- and S. pneumonia– mediated pneumonia and skin and soft tissue infections (SSTIs) Dominique Missiakas, PhD • Broad-spectrum Gram-positive small molecule antibiotic: lipoteichoic acid synthase (LtaS) inhibitor targets a critical cell wall component • Demonstrated robustness against the development of resistance in laboratory screens
  5. 5. Antibody therapeutics and vaccines UChicago antibodies directly target the repertoire of pathogen immune-evasion mechanisms that have undermined staphylococcal and influenza vaccines in the past. UChicago labs lead in the study of antigens critical to these pathways and in the development of protective antibody binders of these antigens. MRSA MRSA Mutated antigen restores effective antibody response Representative Technologies Olaf Schneewind, MD, PhD • S. aureus anti-Protein A (SpA) antibody vaccine and therapeutic: blocks S. aureus SpA surface protein to promote opsonophagocytic killing, block immune evasion, and enable protection against recurrence (adjuvant) • S. aureus IsdA, IsdB, Coa, ClfA, vWbp antibodies show protection against S. aureus in a lethal challenge model Patrick Wilson, PhD • Library of fully human pan-neutralizing antibodies that can effectively target a wide variety of influenza strains (H1N1, H3, H7, H9 varieties) • Cell-culture platform for rapid vaccine generation targeting the H7 flu strain
  6. 6. Subunit and Live Vaccines Superantigens, toxins, immune system modulators, clotting factors, and proteins involved in abscess stability all contribute to severe disease expression during S. aureus infection. UChicago has assembled a portfolio of subunit vaccine antigens whose use alone can limit the disease severity and which in combination have the potential to prevent or clear infections. Combo vaccine prompts protects against severe disease MRSA Representative Technologies Olaf Schneewind, MD, PhD S. aureus vaccines and therapeutics • Non-toxigenic Sbi subunit vaccine • Hybrid Coa subunit vaccine • EsxD subunit vaccine • EsaC subunit vaccine • ClfA/Coa vaccine/ thrombin inhibitor combination therapy Y. pestis (Plague) vaccine • LcrV-based vaccine, in pre-IND authorization review ahead of a Phase I trial B. anthracis (Anthrax) vaccine • PDGA-D4 sortase-conjugated subunit vaccine based on a component of the anthrax protective antigen (PA) Live attenuated S. aureus animal vaccine • variant S. aureus strain vaccine for the prevention and treatment of bovine mastitis
  7. 7. Platform Technologies Novel UChicago platforms allow a consistent approach to be used against a variety of pathogens and diseases reducing risks and costs. The potent peptide vaccine adjuvant platform offers great flexibility whereas the HMW-PEG-based virulence suppression platform prevents a range of diseases and complications associated with surgery or implants. Fibrilizing peptide platform enhances antibody response Representative Technologies Joel Collier, PhD • Inducible fibrilizing conjugate peptide adjuvant that slows clearance and elicits a strong immune response • Defined composition and a defined method of action distinct from alum or lipid-based adjuvants Benoit Roux, PhD • Recombinant OmpF porin for the delivery of penicillin- or carbapenem-derived antibiotics to Gram-negative bacteria John Alverdy, MD • Midway Pharma is developing a HMW-PEG-based platform for microbiome-mediated disease associated with gastrointestinal (GI) disorders and radiotherapy • Alverdy’s second class of HMW-PEG derivatives treat microbiome-mediated anastomotic leak following GI surgery
  8. 8. Available Technologies Resistance-evading small molecule anti-infectives UCHI 2215 Daum Antibiotic potentiator of oxacillin sensitivity UCHI 2153 Topical small molecule ADAM10 inhibitor for the Bubeck treatment of toxin-mediated SSTIs (S. aureus, S. Wardenburg pneumonia) UCHI 2102 Missiakas Broad-spectrum Gram-positive antibiotic: lipoteichoic acid synthase inhibitor Multiple leads identified. Potency assays and animal proof of concept studies underway Lead optimization in progress Antimicrob Agents Chemother, 2011 Improved oxacillin treatment outcomes in experimental skin and lung infection by a methicillin-resistant Staphylococcus aureus isolate with a vraSR operon deletion. Nature Medicine, 2011 A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice. PNAS, 2013 Lead optimization in progress Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria. UCHI 2056 Humanized anti-SpA antibody therapeutic vaccine Schneewind against S. aureus Commencing GMP manufacturing; efficacy demonstrated in murine challenge model, promotes OPK in human blood Infection and Immunity, 2012 UCHI 2115 Monoclonal antibodies against S. aureus IsdA, IsdB, Schneewind Coa, ClfA that protect against S. aureus infection Lead CDRs identified, efficacy demonstrated PLOS Pathogens, 2010 Contribution of coagulases towards Staphylococcus aureus disease in murine challenge model and protective immunity. Antibody-based therapeutics and vaccines Protein A-specific monoclonal antibodies and prevention of Staphylococcus aureus disease in mice. UCHI 2017 A direct thrombin inhibitor in combination with anti- Lead CDRs identified, efficacy demonstrated PLOS Pathogens, 2011 Preventing Staphylococcus aureus sepsis through the inhibition of in murine challenge model Schneewind ClfA mAbs protects against S. aureus infection its agglutination in blood. TNT-0220 Wilson Fully human monoclonal pan-influenza vaccine antibodies against emerging strains of flu Efficacy demonstrated PNAS, 2012 Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Subunit vaccines Infection and Immunity, 2012 UCHI 2133 Recombinant subunit S. aureus vaccine antigens Schneewind (non-toxigenic Sbi, hybrid Coa, EsxD, EsaC) Efficacy demonstrated in murine challenge model UCHI 2055 Sortase-conjugated capsule (PDGA)-protective Schneewind antigen (D4) B. anthracis (anthrax) vaccine Vaccine, 2012 Proof of concept efficacy studies completed Sortase-conjugation generates a capsule vaccine that protects UCHI 1239 LcrV-based Y. pestis (Plague) vaccine Schneewind UCHI 1976 McLeod Peptide vaccine for Toxoplasma gondii Coagulases as determinants of protective immune responses against Staphylococcus aureus. guinea pigs against Bacillus anthracis. In pre-IND authorization review ahead of a Phase I trial Vaccine, 2011 Prevention of pneumonic plague in mice, rats, guinea pigs and nonhuman primates with clinical grade rV10, rV10-2 or F1-V vaccines. Human Immunology, 2012 Proof of concept efficacy studies completed Toxoplasma gondii HLA-B*0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits…
  9. 9. Available Technologies Live attenuated strain vaccines UCHI 2137 Live attenuated S. aureus strains Schneewind Optimizing the strain genetics mBio, 2013 Role of Protein A in the Evasion of Host Adaptive Immune Responses by Staphylococcus aureus. Platforms: adjuvants, delivery technologies UCHI 2191 Roux UCHI 2079 Collier Recombinant porin as a method of delivering antibiotics to Gram-negative microbes Fibrilizing domains act as adjuvants when fused to small protective epitopes or antigens UCHI 978 Alverdy Multicomponent Intestinal Preparation Solution Designed to Prevent Gut-derived Sepsis UCHI 2152 Alverdy High molecular weight PEG derivative s for the treatment of anastomotic leak Proof of concept studies underway Proof of concept studies underway Initial proof of concept studies completed. Additional studies and marketing efforts underway Structure, 2013 The binding of antibiotics in OmpF porin. PNAS, 2010 A self-assembling peptide acting as an immune adjuvant. Am J Physiol Gastrointest Liver Physiol., 2009 Oral PEG 15-20 protects the intestine against radiation: role of lipid rafts. PloS One, 2012 Initial proof of concept studies completed. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak.
  10. 10. How to Partner with the University of Chicago Contact UChicagoTech, the Center for Technology Development & Ventures, to learn more. We build strong industry partnerships to successfully bring innovation to the marketplace. UChicagoTech can connect you to emerging technologies and fieldadvancing researchers that may inform and enrich your own innovation efforts. We value your involvement at every stage of the invention pipeline, from idea to tangible asset. For more information, visit us at tech.uchicago.edu or contact anyone on the Infectious Disease team. Thomas Jones, PhD Associate Project Manager Phone: 773-834-3208 tjones@tech.uchicago.edu Divya Varshney, MBA Chief Marketing Officer Phone: 773-702-8696 dvarshney@tech.uchicago.edu Glenna Smith, PhD Project Manager Phone: 773-702-6122 gsmith@tech.uchicago.edu

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