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Unlocking The Immune System

Bioniz’s platform for rational peptide design is a robust system for a new generation of biologics that can modulate selected subsets of those families. Our lead family is the gamma-chain of cytokines, Interleukins 2, 4, 7, 9, 15, & 21.
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Clinical Approval Overview

Pipeline

BNZ-1: IL-2, IL-9, & IL-15 Inhibitor

Lead Candidate Focusing On Autoimmunity and Cancer

“Benzie One” is Bioniz’s lead compound and is an inhibitor of three interleukin cytokines known to be specifically hyper-activated in the orphan autoimmune disease state, HAM/TSP, which is a disease with an MS-like clinical presentation for which there is no effective therapy. Bioniz is partnering with the NIH to start clinical trials for these patients in 2016, and a Bioniz iswe are communicating with an expert in Large Granulocytic Leukemia (LGL) in order to explore BNZ-1’s potential for the inhibition of lymphocytic hemolytic cancers.

Current Progress Includes

  • Easy manufacturing processes compared to MABs

  • Action Proven in Journals JBC and PNAS

  • Mechanistically Appropriate To Lead Indications

  • Excellent Pk and Toxicity Results

BNZ-2: IL-15 & IL-21 Inhibitor

A Multiple Inhibitor With Potential for Inflammatory Diseases of the Gut

BNZ-2 inhibits two cytokine pathways and is of interest for treatments in conditions like Celiac disease, in which IL-15 and IL-21 are known to have a role. This could come as a relief to many patients who suffer from these conditions since there is no current recognized therapeutics in the space.

Current Progress Includes

  • Highly Applicable to inflammatory diseases of the GI tract

  • Preliminary In Vivo Model Data

  • Oral Formulation for Targeting Specific Region

  • Trials Expected With U of Chicago Celiac Disease Expert

BNZ-3: IL-4, IL-9, & IL-21 Inhibitor

An Early Stage Compound With Large Market Potential

BNZ-3 is an early stage asset targeting IL-4, IL-9, & IL-21 cytokines. It has potential for a wide range of prevalent diseases including COPD, Asthma, Sjögren’s syndrome, & Lupus.

Indications

Autoimmune Indications

HTLV-1 Associated Myelopathay/Tropical Spastic Paraparesis (HAM/TSP)

Overview

HAM/TSP is a rare autoimmune disease caused by infection of T-Cells with the HTLV-1 retrovirus. Although the prevalence of the virus in US blood donors has been shown to be 1 in 10,000, only 0.25-3.8% of infections progress to HAM/TSP, while another 2-3% develop aggressive adult T-cell leukemia (ATL). Clinically indistinguishable from MS for a variety of reasons, HAM/TSP is most often differentiated by the presence of high proviral loads in the blood. While HTLV-1 is a blood-born pathogen, most carriers will remain completely asymptomatic.

As an orphan autoimmune indication, HAM/TSP is an ideal first indication both for its under-addressed patient population, as well as for the relevance of cytokine inhibitor-mediated CD4+ and CD8+ T-cell interruption as a proof of concept to larger, and also undertreated, autoimmune indications.

0 Patients

have HAM/TSP in the US

0 People

are infected with HTLV-I or -II worldwide

Disease Quick Facts

Causes

Although HAM/TSP is associated with HTLV-I infection, the disease pathogenesis does not occur through viral replication. Indeed, no active viral replication has been detected in these patients, which explains the failure of anti-viral drugs in therapeutic trials. It has been accepted by the scientific community that HAM/TSP is caused by continuous hyper activation of immune response to viral antigens. Therefore, this disease resembles autoimmune diseases in general. Many publications highlight the central role of cytokines, in particular IL-2 and IL-15, in the disease pathogenesis. These two cytokines drive the proliferation of viral-infected T-cells and expansion of viral specific cytotoxic cells in the peripheral blood. Once these two cell populations pass through the compromised BBB, the cytotoxic cells attack the viral infected T-cells, which result in the release of inflammatory cytokines and generation of lesions in the CNS.

Symptoms

The main symptom of HAM/TSP is paraparesis, the P in the name, which refers to partial paralysis and neurological conduction anomalies in the legs, but HAM/TSP is also characterized by a range of other symptoms. In summary, HAM/TSP is a debilitating disease where patients slowly lose their ability to walk and will eventually become wheelchair bound.

  • Back pain
  • Gait Disturbance
  • Bladder/bowel or sexual dysfunction
  • Neuropathic pain
  • Comorbidity with other recognized autoimmune conditions such as myositis, peripheral neuropathy, uveitis, arthritis, Sjorgren’s Syndrome, and alveolitis

Standard of Care

There is no FDA approved drug for HAM/TSP. Clinicians resort to the use of steroids to control the patient’s symptoms, an approach that has shown only transient effects. In Japan, interferon-α has been approved for this disease, which has shown some short term efficacy.

Healthcare Burden

HAM/TSP represents an orphan disease and an unmet medical need. The disease dramatically reduces quality of life and places a burden of missed opportunities, misery, and ineffective care on patients and on society. Bioniz hopes to provide a therapy that can return quality of life to these patients, allow them to be more active again, and reduce the burden of treating symptoms on the healthcare system by treating the cause instead.

Celiac Disease

Celiac disease (CD) is a genetically-linked and chronic autoimmune disease characterized by inflammation of the small intestine in reaction to exposure to gluten, an immune-recognizable (immunogenic) protein found in grains such as wheat and barley that are frequently used to make bread and other carbohydrate products.

Although the prevalence of CD is estimated to be from 1 in 133 up to 1 in 100 people, only 20% of patients are typically diagnosed, meaning that up to 2.5 million Americans may have undiagnosed CD. CD can occur in men and women of any age, but misdiagnosis remains a frequent problem for CD sufferers. A subgroup of CD patients have severe disease, even when they observe a strict gluten-free diet. These patients have what is referred to as refractory celiac disease. A small fraction of these patients will develop an extremely aggressive and fatal Entereopathy T-cell Leukemia. Therefore, it is critical to develop therapies to treat refractory celiac disease.

0 Americans
May Have CD

Disease Quick Facts

Symptoms and Clinical Course

CD pathology results from an immune reaction to gluten in the small intestine that results in the release of inflammatory cytokines that causes a local immune recruitment that attacks the structures of the bowel called villi. Villi are small “finger-like” protrusions that increase the surface area of the intestine to provide an interface across which nutrients can be efficiently absorbed as digested food is processed. As the villi are inflamed, the bowel reacts with symptoms including bloating, diarrhea, and extreme pain. Less local effects may be driven by immune activation and nutrient malabsorption and include:


  • Anemia and osteoporosis (calcium and iron uptake) as well as other vitamin deficencies
  • Infertility and miscarriage
  • Lactose intolerance, pancreatic insufficiency, and GI cancers
  • Central and peripheral nervous system disorders including ataxia, epileptic seizures, migraines, neuropathies, dementia, myopathy, and multifocal leucoencephalopathy
The pathology of CD is complex and under ongoing investigation. Several current investigations into the key immune signaling behaviors that sustain CD are focusing on the role of IL-15 and IL-21, which are targets for Bioniz’s BNZ-2 compound. Bana Jabri, who is a member of Bioniz’s Scientific Advisory Board, and who is a leader in Celiac disease in her role as the director of the University of Chicago’s Celiac Disease Center, leads the investigation of BNZ-2’s clinical trials.
Mechanism


Cytokines

Treatment

Currently, no treatment exists for sufferers of a CD diagnosis except to abstain from contact with any gluten containing products.

Healthcare Burden

While the symptoms of CD can be controlled by avoiding gluten, the numerous undiagnosed patients in the US are estimated to each cost an additional $991 per year. On an individual basis, for those patients with severe CD, the lost opportunities, incredible discomfort, and the risk of developing Entereopathy T-cell Leukemia will cost far in excess of this value.

Additional Resources

  • Celiac Disease Foundation Info
  • Beyond Celiac
  • Celiac Disease: An Immunological Jigsaw
  • Is Non-Celiac Gluten Sensitivity a Real Thing? by Healthline news

Cancer Indicaitons

Large Granular Lymphocytic (LGL) Leukemia

Overview

LGL leukemia is a rare non-hodgkins cancer of the lymphoid lineage that is characterized by an uncontrolled proliferation of T-cells (CD3+ cytotoxic) or Natural Killer (NK) cells (CD3-) and that is frequently observed to co-occur with autoimmune disease. Although the causation for LGL remains unknown, experts such as Dr. Thomas Loughran, Jr. have constructed complex immune system models to examine the possible interplay of regulatory mechanisms in LGL to better inform avenues of investigation. Although the majority of patients with LGL begin with mild symptoms, most patients will eventually require treatment for their condition, and some patients’ conditions may progress to the aggressive form of the disease, which is rapidly progressing and severe.

0%
as much as 5% of lymphoproliferative disease is estimated to be LGL

Disease Quick Facts

Symptoms and Clinical Course

LGL has two clinical stages, chronic and acute. The majority of patients are in the chronic stage, but they may later transition to the acute stage, which is a more aggressive form of the disease with a very poor prognosis. Therefore, it is critical for chronic LGL patients to be diagnosed quickly and treated appropriately to prevent the transformation of the disease from chronic to acute.

The clinical presence of the disease is diagnosed by elevated lymphocytes in the blood (lymphocytosis) and bone marrow of large white cells that have “granules” that become visible under a microscope when stained. Hyper-aggressive proliferation of these cells in the bone marrow effectively pushes out cells of other functional lineages in the marrow, where they are created, resulting in lowered red blood cells (anemia), lowered white blood cells called neutrophils (neutropenia), and lowered platelets, the fraction of the blood that clots, and that prevents internal bleeding into the organs (thrombocytopenia). Symptoms also include splenomegaly (enlarged spleen), fever, night sweats, loss of weight, and in rare cases, swollen lymph nodes or liver.

Treatment

There is no FDA approved standard of care for LGL. The standard of care is limited to immunosuppressive agents such as steroids, cyclosporine, cyclophosmaide, and methotrexate. These agents do not treat the disease, rather mainly manage the symptoms.

Link With Autoimmune Disease

Although LGL itself is not considered autoimmune, in 20% of cases, it is associated with Rheumatoid Arthritis, which is sometimes also treated with methotrexate. LGL and autoimmunity share common regulatory mechanisms in so far as that the proliferation, movement, and activity of T-Cells and NK cells in the immune system are governed by cytokine signaling.

Healthcare Burden

While some patients may be relatively asymptomatic, the majority will eventually require treatment for anemia, neutropenia, and thrombocytopenia, and those that enter an aggressive phase of the disease will require aggressive cancer treatments in response, which if not effective, may mean the patient’s death. While the disease has different clinical manifestations, the burden of treatment on patients is significant whether they are in chronic or in a more aggressive stage of the disease.

Additional Resources

  • NIH HAM/TSP Site
  • Leukemia & Lymphoma Society
  • UVA Patient Registry
  • Orphanet
  • Blood Journal: How I Treat LGL