ALTB-168

Therapeutic Area Indication

Therapeutic Area

Product Overview
ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, preferentially inducing the down regulation of late-stage, chronically activated T cells. This novel antibody effectively targets chronic pathogenic T cells while fully maintaining host defense, leading to durable clinical efficacy with a potential to reduce risks of adverse events such as infection and cancer. These two characteristics, which have been well demonstrated in our clinical studies, offer a sustainable competitive advantage over existing therapies.

ALTB-168 has demonstrated signs of clinical efficacy in Phase II clinical trials for T-cell mediated diseases such as psoriasis, psoriatic arthritis and ulcerative colitis. This innovative drug candidate has the potential to bring game-changing benefits to patients with many other T-cell mediated diseases. We have also completed a phase I study in patients who develop steroid/treatment-refractory acute graft versus host disease (SR/TR-GVHD) after allogeneic hematopoietic cell transplantation (HCT), as well as an ongoing clinical study in the front-line setting of acute GVHD.
Competitive Advantage of ALTB-168

01

A potential to reduce risks of adverse events such as infection and cancer

Cytokine inhibitors, the most popular bio-therapeutics on the market, can help patients relieve symptoms associated with inflammatory diseases. However, increased risk of infection has often been noted in those inhibitors targeting immune-related cytokines such as TNF-alpha, IL-12/23, IL-6 and IL-17. Mechanistically, by targeting late-stage chronically activated T cells, our approach has the potential to reduce risks of adverse events such as infection and cancer. Accumulated clinical evidence demonstrated no signs of elevated infection risks post ALTB-168 treatment.

02

Alternative therapy for the patients who either did not respond or lost response to existing therapies

Close to 50% of RA and PsA patients treated with existing cytokine inhibitors for at least 6 months failed to achieve the 50% (ACR50) improvement criteria. Furthermore, more than 50% of patients undergoing long-term treatment of TNF-alpha inhibitors lose response to the drugs. Therefore, an alternative therapeutic agent like ALTB-168 is well positioned to treat those patients who no longer respond to or discontinue the use of these drugs.

03

A potential standard of care treatment in immunology and inflammation

Current treatments systemically suppress the immune system, leaving patients vulnerable to infection and other adverse effects. Our immune checkpoint enhancers, however, preferentially target late-stage, chronically activated T-cells with the aim to restore the immune system to a state of balance potentially providing meaningful clinical benefits to those patients with unmet medical needs.

Indication

Psoriasis Psoriatic Arthritis Ulcerative Colitis Steroid/Treatment Refractory Acute Graft Versus Host Disease Acute Graft Versus Host Disease

Psoriasis

1

  • PRECLINICAL

  • PHASE I

  • PHASE IIA

    Phase II

  • PHASE IIB

  • PHASE III

Introduction

Psoriasis is a complex, chronic relapsing and inflammatory skin disorder affecting 2-3% of the general population worldwide. Psoriasis vulgaris (chronic plaque psoriasis), the most common type of psoriasis, primarily features dry, sharply demarcated, raised erythematous skin plaques covered by silvery scales. Cumulated evidence suggested that dysfunctional helper T cells (Th1, Th17, Th22, and Treg cells) are indispensable factors in psoriasis development.

ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, which preferentially induces down regulation of late-stage, chronically activated T cells. As a consequence, the treatment of ALTB-168 can lead to amelioration of multiple T-cell-driven autoimmunity and inflammation, including psoriasis.

Two phase IIa studies with ALTB-168 were completed in 2014 and 2015. In both studies ALTB-168 demonstrated signs of clinical efficacy in patients with moderate to severe chronic plaque psoriasis.

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Psoriatic Arthritis

2

  • PRECLINICAL

  • PHASE I

  • PHASE IIA

    Phase II

  • PHASE IIB

  • PHASE III

Introduction

Psoriatic arthritis (PsA) is a clinically heterogeneous chronic inflammatory disease, comprising a range of musculoskeletal (joints, nails, and entheses) and dermatological manifestations associated with impaired physical function and poor quality of life. Evidence supports that T cells plays a vital role in initiating and substantiating psoriatic arthritis by generating inflammatory cytokines which stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone.

ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, which preferentially induces down regulation of late-stage, chronically activated T cells. Consequently, the treatment of ALTB-168 can lead to amelioration of multiple T-cell-driven autoimmunity and inflammation, including psoriatic arthritis.

Indeed, a phase IIa study with ALTB-168 was completed in 2016. From 15 PsA patients completing 7 courses of ALTB-168 treatment, significant improvement was seen in 8 patients at week 12 (primary endpoint), with some responders maintaining significant efficacy through week 24.

These encouraging results will now need confirmation in an appropriate Phase II trial with a suitable target population and expanded number of patients.

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Ulcerative Colitis

3

  • PRECLINICAL

  • PHASE I

  • PHASE IIA

    Phase II

  • PHASE IIB

  • PHASE III

Introduction

Ulcerative colitis (UC), characterized by the hallmark clinical symptoms of bloody diarrhea, rectal urgency, and tenesmus, is a chronic inflammatory disease affecting the colorectal mucosa. The underlying pathogenesis of UC is complex, and accumulating evidence suggests that environmental factors contribute to triggering an overly active or dysregulated T-cell mediated immune-inflammatory response in genetically predisposed individuals, which eventually leads to mucosa damage.

ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, which preferentially induces down regulation of late-stage, chronically activated T cells. Consequently, the treatment of ALTB-168 can lead to amelioration of multiple T-cell-driven autoimmunity and inflammation, including ulcerative colitis.

Phase 2a anti-TNF α and/or anti-integrin refractory/intolerant Ulcerative Colitis trial has been completed, with signs of clinical efficacy demonstrated. Continued UC development is planned with ALTB-268.

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Steroid/Treatment Refractory Acute Graft Versus Host Disease

4

  • PRECLINICAL

  • PHASE I

    Phase I

  • PHASE IIA

  • PHASE IIB

  • PHASE III

Introduction

Graft-versus-host disease (GvHD) is a multisystem disorder involving tissue inflammation most frequently in the skin, gastrointestinal track and the liver that occurs after allogeneic hematopoietic cell transplant (HCT), and is the major complication of hematopoietic cell transplantation (HC) that accounts for most non-relapse mortality (NRM) and limits the success of HCT. It is known that the disease is initiated by donor T-cells recognizing the host as foreign and mounting a deleterious immune response against antigens found in the host.

ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, which induces down regulation of activated T cells. Consequently, the treatment of ALTB-168 can lead to amelioration of multiple T-cell-driven autoimmunity and inflammation, including aGvHD.

ALTB-168 has completed a phase 1b multi-dose trial in adults with steroid refractory acute GVHD (patient who failed steroid) and treatment refractory acute GVHD (patient who failed steroid plus one systemic treatment such as ruxolitinib). The FDA has granted Fast Track Designation to ALTB-168 in SR-aGVHD and Orphan Drug Designation in SR-aGVHD.

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Acute Graft Versus Host Disease

5

  • PRECLINICAL

  • PHASE I

    Phase I

  • PHASE IIA

  • PHASE IIB

  • PHASE III

Introduction

Graft-versus-host disease (GvHD) is a multisystem disorder involving tissue inflammation most frequently in the skin, gastrointestinal track and the liver that occurs after allogeneic hematopoietic cell transplant (HCT). It is the major complication of hematopoietic cell transplantation (HC) that accounts for most non-relapse mortality (NRM) and limits the success of HCT. It is known that the disease is initiated by donor T-cells recognizing the host as foreign and mounting a deleterious immune response against antigens found in the host.

ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, which induces down regulation of activated T cells. Consequently, the treatment of ALTB-168 can lead to amelioration of multiple T-cell-driven autoimmunity and inflammation, including aGvHD.

ALTB-168 is being studied in an ongoing investigator sponsored phase 1 study in front line acute GVHD to determine the maximum tolerated dose and safety of ALTB-168 for the treatment of Minnesota standard-risk aGVHD at the Medical College of Wisconsin.

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