ON IMAGING PLATFORM

ONM-100 Addresses Unmet Need for Real-Time Cancer Resection Imaging

  • Currently, surgeons rely on relatively imprecise imaging results conducted prior to surgery to identify the general location, scope of tumor, and lymph node invasion
  • In the OR, surgeons typically rely on use of cameras, visual inspection and palpation to identify tumors, and the margin between tumor and normal tissue
  • Literature and our clinical experience indicate that the current standard of care for tumor resection can result in positive margins and satellite tumors left behind
  • ONM-100 provides surgeons with real-time, sharp visualization of tumors improving surgical outcomes
ONM-100 Clinical Success Demonstrates Precision of Micelle Technology

Key Clinical Findings:

  • Very well tolerated, no product related SAEs
  • Florescence seen across all 6 tumor types in ~45pts- Breast,Colorectal,Esophageal,Head&Neck, Ovarian, Prostate
  • Clear, real-time delineation of tumor
  • Phase 1 results:- 100%responserate(abilitytoidentifytumors)- IdentifiedoccultdiseasemissedbySOCin ~30% of patients
  • Dose proportional PK, 44±16 hr half-life
  • FDAFastTrackdesignation
ONM-300: Technology Also Employed in Next Generation PET Imaging Agent
  • IV injectable whole body non-invasive tumor imaging using 64Cu
  • Precision imaging of tumors poorly imaged by FDG-PET incl. brain
  • Eliminates false positives from brown fat, inflammation, striated muscle
And...Clinical Imaging Experience Validates Cancer Therapeutic Platforms and Associated Programs
  • IV injectable whole body non-invasive tumor imaging using 64Cu
  • Precision imaging of tumors poorly imaged by FDG-PET incl. brain
  • Eliminates false positives from brown fat, inflammation, striated muscle
ON Imaging

Advancing Diagnosis and Surgical Outcomes

Proprietary Product Candidates

ONM-100 – Real time surgical imaging

ONM-300 – Next gen PET Key Partners

Grants from CPRIT and NIH

ON-BOARDTM

Tumor-Specific Delivery of Therapeutics

ONM-400 – Next gen IL-2

ONM-401 – Small molecule

2 Large Pharma

Collaborations

OMNITM

Therapeutic Immune Activation

ONM-500 – T-cell activation and single agent activity against
ONM-401 – Small molecule
solid tumors

$15.4m CPRIT grant

ON-BOARD™ PLATFORM

Attributes & Benefits of ON-BOARD ™ Platform

HIGHLY TUNABLE PLATFORM
Tunable core hydrophobicity, core and shell functional groups – suitable for encapsulation, conjugation

LARGE UNIVERSE OF POTENTIAL DRUG TARGETS
Demonstrated ability to deliver small molecules, antibody fragments and cytokines

INCREASED TUMOR PENETRATION, EFFICACY
Unique properties provides improved penetration compared to traditional polymeric approaches

REDUCED TOXICITY
Improved therapeutic window due to limited exposure of payload to normal tissues – offers potential to improve upon discontinued, existing and developmental compounds

AVOIDS LIMITATIONS & COMPLEXITY OF ACTIVE TARGETING
Eliminates need for active targeting with mAbs/other agents that limit therapeutic utility

ONM-400: Tumor-Specific Delivery of IL-2

OMN-400 addresses shortcomings of other IL-2 product candidates:

  • Highly specific tumor delivery
  • High loading capacity, instantaneous IL-2 release leads to high tumor accumulation
  • Effective payload “shielding” from normal tissues, avoids systemic exposure and IL-2 toxicity
ON-BOARD delivery avoids requirement for mutein forms of IL-2

  • Low tumor concentrations achieved with WT IL-2 led to use of muteins to minimize Treg regulation 
  • ONM-400 provides high tumor concentrations resulting in preferential activation of T effectors over Tregs eliminating the need for muteins
  • ONM-400 avoids off target binding to normal tissues eliminating need for mutein forms
  • ONM-400 optimizes delivery of a commercially validated rhIL-2, reducing clinical risk 
ONM-400 Delivery Enables Favorable PK and Targeted Tumor Delivery
  • Distinctly different accumulation pattern for ONM-400 versus free IL-2 
  • ONM-400: Strong preferential accumulation in tumors over other tissues/organs
  • Free IL-2: Predominantly accumulates in kidney and bladder
  • Persistent tumor accumulation @ 24 hr timepoint
  • ONM-400 accumulation in tumor is still seen at 24 hrs, while free IL-2 has cleared 
  • Significant extension of plasma half-life
  • – ONM-400 t1/2 >12 h vs. free IL-2 t1/2 <0.5 h 
ONM-400 Preliminary Preclinical Data
  • ONM-400 shows higher response rate with more complete tumor regression vs. IL-2 alone at the same dose
  • ONM400 in a preliminary study as a single agent, shows greater single agent survival benefit vs. competitors
  • ONM-400: 60% of animals were tumor free at 36 days vs. 0% for IL-2
  • NKTR-142 (Nektar) in vivo preclinical data indicates limited single agent efficacy
  • THOR-701 (Synthorx) in vivo preclinical data indicates virtually no single agent efficacy
Application to Small Molecules: ON-BOARD™ Improves the Therapeutic Index of MCT-1 Inhibitor
  • MCT-1 Inhibitor held promise as an effective broadly applicable cancer therapy; however, toxicities in Ph 1 led to its being dropped
  • ON-BOARD™ micelle encapsulation significantly improves therapeutic index of MCT-1 Inhibitor alone
ON-BOARDTM/MCT-1 Inhibitor Demonstrates Efficacy, Anti-PD-1 Synergy and Improved Safety
OMNI™ Delivers Payload Selectively to Lymph Nodes Following Subcutaneous Injection
OMNI
  • OMNI micelles localize to the lymph node following subcut injection where they are primarily taken up by dendritic cells
  • OMNI can deliver tumor associated antigens, small molecules, cyclic peptides 
OMNI™ Binds to STING Through a Different Binding Site from cGAMP, other Cyclic Di-Nucleotides
  • Endogenous STING agonists (cGAMP or other CDNs) bind to the STING dimer interface covered by a lip of four-stranded antiparallel β sheet (human AA 219-249)
  • OMNI binds to STING through a distinct surface binding site E296/D297 on the α5 helix
.....Resulting in a Strong Immune Response
  • OMNI™  induces STING condensation and immune activation through polyvalent interactions
  • Enabling prolonged and sustained STING activation
  • Activates cGMP-resistant STING variants 
ONM-500.H1: OncoNano’s OMNI™ Program for HPV Related Cancers Supported by CPRIT

• Awarded $15.4 million grant from CPRIT to advance product development
• ONM-500.H1 uses the full-length E6 and E7 (HPV type 16) oncoproteins to cover the multi-immunogenic T-cell epitopes in patients 

ONM-500.H1 [OMNITM + E6 and E7 recombinant (HPV type 16)] shows significant TC-1 tumor growth inhibition (left) over control groups and 100% survival with and without anti-PD1 treatment

CKD Overview

Chronic Kidney Disease (CKD)

  • 30 million people or approximately 15% of the U.S. Adults have CKD. (CDC 2017)
  • Almost one out of every 7 adults 30-64 years of age is expected to develop CKD during their lifetime
  • While dialysis-dependent CKD accounts for only 0.5% of the U.S. population, fee-for-service expenditures for Medicare beneficiaries with dialysis-dependent CKD exceeded 30 billion dollars in 2013, or over 7% of the Medicare paid claims cost
  • Escalation in healthcare expenditures associated with CKD starts prior to the requirement for dialysis and treatment cost escalate as non-dialysis dependent CKD progresses
  • CKD is a significant unmet medical need, and the financial burden has reached insurmountable proportions for patients and the U.S. healthcare system. In 2018, Medicare costs $119 billion, and similar public cost burdens likely exist in the EU and Asia.
Facts about

Coronavirus 2019 (COVID-19)

  • A respiratory tract infection caused by a virus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
  • First discovered in 2019, COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020
  • Within the first 4 months of 2020, over 3 million people were infected worldwide and over 230,000 died from COVID-19
  • Almost a year later, there are more than 103 million cases worldwide and over 2.2 million deaths.
  • Spread through respiratory droplets via person-to-person contact or touching a surface on which infected droplets have landed
  • Symptoms may not be present up to 14 days after infection, increasing the risk of unintended transmission
  • An enveloped virus similar to other coronaviruses like SARS and Middle East respiratory syndrome (MERS); this envelope helps the virus enter cells and protects the virus from destruction 
  • Once inside the cell, the virus takes over the host cell machinery and multiplies, leading to increased viral load and spreading of the virus to other parts of the body
  • Causes heart and kidney injury, which are associated with COVID-19-related mortality; acute kidney injury has been reported in ~15% of hospitalized patients; cardiovascular complications have been reported in ~20% of hospitalized patients
  • Individuals at high risk for disease progression are those who are >60 years of age; have underlying health problems such as lung disease, hypertension, cardiovascular disease, kidney disease, diabetes, obesity, malignancy; or are taking immunosuppressants

Product Pipeline

RBT-1:  Iron Sucrose (FeS) and
Stannus Protoporphyrin (SnPP)

RBT-1 is a newly developed combination product designed to induce preconditioning of the kidney, upregulating production of protective proteins to prevent AKI during cardiac surgery.

Preclinical: Complete. Conditioning Rx protects against AKI, hepatic injury,and cardiac injury in response to AKI in animal models. Plasma and urine HO-1 assay serves as a bioassay of gene induction.

Phase I is nearly complete. Early data is encouraging.

RBT-2: Optimized Tetrahydrodiferuloylmethane

RBT-2  (optimized tetrahydrodiferuloylmethane) is an active metabolite of a widely known antioxidant that reduces CKD progression by restoring cellular homeostasis and reducing inflammation and fibrosis development. Protective effects of RBT-2 have also been observed in the heart. RBT-2 is effective in different types of CKD, including diabetes mediated CKD and sub-total nephrectomy.

RBT-3:  Iron
Sucrose (FeS)

RBT-3 is being developed to treat iron deficiency anemia. RBT-3 rapidly increases plasma ferritin without inducing nephrotoxicity or cardiotoxicty. Phase II development with RBT-3 is expected to begin in 1H, 2020.

RBT-9: Treatment of
Enveloped Viruses

Rénibus Therapeutics is developing a novel antiviral therapy RBT-9 (Stannous protoporphyrin [SnPP]) for the treatment of COVID-19 at the early stage (Stage I) of infection in patients who are at high risk for disease progression. RBT-9 reduces the viral load of several enveloped viruses and protects organs by mitigating viral-induced inflammation and upregulating the production of protective proteins. Our therapeutic goal is to both decrease SARS-CoV-2 viral loads and upregulate intrinsic tissue defense pathways, thereby preventing SARS-CoV-2-mediated organ injury and improving medical outcomes.

Rénibus Therapeutics has received a Fast Track designation from the FDA for the use of RBT-9 in the treatment of COVID-19. The Phase II trial is now enrolling.

Renibus Therapeutics has received a Fast Track designation from the FDA for the use of RBT-9 in the treatment of COVID-19. The Phase II trial is now enrolling.

Rénibus News

Presentations at the American Society of Nephrology Kidney Week 2020

RBT-9 Antiviral Activity Against SARS-CoV-2

Renibus Therapeutics Announces Abstract Presentation at the 2020 European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Annual Congress

A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKD,

Richard A. Zager, Ali C.M. Johnson, Alvaro Guillem, Jeff Keyser and Bhupinder Singh. CJASN April 2020, CJN.15951219; DOI: https://doi.org/10.2215/CJN.15951219

A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKD

Richard A. Zager, Ali C.M. Johnson, Alvaro Guillem, Jeff Keyser and Bhupinder Singh

Renibus Therapeutics Receives FDA Fast Track Designation for RBT-9 Treatment in COVID-19

Preclinical studies have shown that RBT-9 protects various organs, including the lung, heart, kidney, and liver. Importantly....

Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure

Tissue preconditioning, whereby various short-term stressors initiate organ resistance to subsequent injury, is well...

Parenteral Iron Sucrose-Induced Renal Preconditioning: Differential Ferritin Heavy and Light Chain Expression in Plasma, Urine and Internal Organs.

Johnson AC, Gooley T, Guillem A, Keyser J, Rasmussen H, Singh B, Zager RA. Am J Physiol Renal Physiol. 2019 Oct 14. doi: 10.1152/ajprenal.00307.2019. [Epub ahead of print] PMID: 31608670

Tin protoporphyrin activates the oxidant-dependent NRF2-cytoprotective pathway and mitigates acute kidney injury

Tin protoporphyrin (SnPP), a heme oxygenase (HO) inhibitor, can paradoxically protect against diverse forms of

Executive Order on Advancing American Kidney Health. The administration is dedicated to advancing kidney health.

The state of care for patients with chronic kidney disease and end-stage renal disease (ESRD) is unacceptable...

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