Cytovia Immuno Oncology

Cytovia

Ceplene

Note: Ceplene approved in Europe and Israel

Ceplene® (histamine dihydrochloride) is administered in conjunction with low dose interleukin-2 (IL-2), for maintenance of first remission in patients with Acute Myeloid Leukemia (AML). It has been shown in clinical studies to prevent leukemic relapses in AML patients in first remission and prolong leukemia-free survival while maintaining good quality of life during treatment.       

AML patients receive intensive induction treatment with chemotherapeutic drugs at diagnosis, and typically become free of detectable leukemia, achieving “complete remission”. However, within 1-2 years the majority (75-80%) of adult patients will experience a relapse of leukemia, of which survival prognosis is extremely poor especially in patients over 60 years of age (15-20%). With ~20000 new cases in the US in 2015, poor prognosis following first remission and no other effective remission therapies currently available, AML represents an orphan indication with particularly high unmet need.

Ceplene® acts by enhancing the immunostimulatory effect of IL-2 and countering ROS-induced dysfunction and apoptosis of T and NK cells, thereby inducing immune-mediated killing of leukemic cells, providing a strong pharmacokinetic rationale for this combination therapy.

A Phase III clinical study of 320 adult patients with acute AML in remission met its primary endpoint of increased leukemia-free survival (p <0.01), indicating that Ceplene® offers an efficacious and tolerable treatment in this population (Blood; The Journal of the American Society of Hematology, volume 108, number 1, pp. 88-96, July 1, 2006).

The European Commission has approved Ceplene® for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia in first remission. Ceplene® has been granted orphan drug status for the treatment of AML by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Additional clinical pharmacology and outcomes data in biomarker-defined sub-populations from a post-marketing study conducted in Europe were presented at ASCO 2016.

 

ceplene arc poster

Crolibulin

CrolibulinTM is a novel small molecule Vascular Disrupting Agent, or VDA, and apoptosis inducer for the intended treatment of patients with solid tumors. With a unique mechanism of action for first line therapy, CrolibulinTM acts as a microtubule destabilizer and specifically blocks blood vessels that carry vital nutrients to tumor sites, thereby selectively targeting and killing tumor cells. In preclinical animal tumor models, combination therapy has demonstrated synergistic activity with cytotoxic drugs as well as anti-angiogenic drugs, such as Avastin. Future development priorities include preclinical confirmation of combination therapies, particularly in the immuno-oncology space, with checkpoint inhibitors and with Avastin.

CrolibulinTM has demonstrated preliminary positive clinical effect in a Phase II study for the treatment of anaplastic thyroid cancer (“ATC”) under a National Cancer Institute collaboration. CrolibulinTM has also shown promising vascular targeting activity with potent anti-tumor activity in pre-clinical in vitro and in vivo studies and in a Phase I clinical trial. To date over 100 patients have been treated with CrolibulintM.

Crolibulin-Immune-Phamaceuticals

Azixa® (verobulin)

Azixa® (verobulin) is a potent, rapidly acting Vascular Disruptive Agent in development for the treatment of primary brain cancers and metastatic tumors with brain involvement.

Azixa® is a novel small molecule drug candidate that acts as a microtubule destabilizing agent, causing arrest of cell division and programmed cell death in cancer cells. Future development priorities include preclinical confirmation of combination therapies, particularly in the immuno-oncology space, with checkpoint inhibitors and with Avastin.

In terms of clinical advancement, two phase 2a clinical studies demonstrated that:

  • Azixa®, in combination with standard chemotherapy, resulted in durable responses with no additive toxicity in patients with glioblastoma multiforme (GBM) or metastatic melanoma.
  • Azixa® in monotherapy resulted in durable responses in GBM patients who had failed both first and second line therapy.

Azixa® has received orphan drug status in the U.S. for the treatment of glioblastoma multiforme (GBM). Preliminary clinical effect was demonstrated in several phase I and pilot phase II studies in patients with brain tumors, melanoma as well as other solid tumors. To date ~167 patients have been treated with Azixa®.

Azixa

In terms of clinical advancement, two phase 2a clinical studies demonstrated that:

  • Azixa®, in combination with standard chemotherapy, resulted in durable responses with no additive toxicity in patients with glioblastoma multiforme (GBM) or metastatic melanoma.
  • Azixa® in monotherapy resulted in durable responses in GBM patients who had failed both first and second line therapy.

Azixa® has received orphan drug status in the U.S. for the treatment of glioblastoma multiforme (GBM). Preliminary clinical effect was demonstrated in several phase I and pilot phase II studies in patients with brain tumors, melanoma as well as other solid tumors. To date ~167 patients have been treated with Azixa®.

 

NanomAb

NanomAb®, are next-generation nanoparticles, which contain thousands of cytotoxic molecules and are conjugated to monoclonal antibodies that recognize specific targets (antigens) in order to enhance the nanoparticles’ specificity, stability and therapeutic efficacy.

Our innovative platform provides a more efficient approach for tumor-specific delivery of cancer therapeutics and immuno-modulatory agents: while current chemotherapies are limited by relatively low antibody to drug ratio and lack of tailored combined therapy, our “next generation antibody-drug conjugate (ADC)” NanomAb technology addresses these challenges by enabling:

  • Significantly higher loadings per particle, allowing for stronger anti-tumor effect
  • Targeted delivery specifically to tumor cells, reducing toxicities and undesirable side effects
  • Higher versatility in both the deliverable drug and the chosen target.

A variety of small molecules, peptides or proteins can be chosen based on sensitivity to cytotoxic agents and delivered inside the nanoparticle. Similarly, the highly targeted monoclonal antibody conjugated to the nanoparticle can be chosen based on tumor antigens, and IMMUNE Pharmaceuticals has already prioritized the development of several immune checkpoint inhibitor-targeted Nanombs. We are expecting validation of manufacturing processes and preclinical proof of concept with these select targets in the immuno-oncology space.

NanomAb-immunepharmaceuticals

Bispecific Antibodies

Our unique bispecific antibody development platform using a novel tetravalent BsAb system provides a new way at generating highly targeted cancer therapeutic agents. With two units with bivalent binding between them, our highly targeted bispecific antibody can be directed at two receptors on one tumor cell or two different tumor cells.  The platform prototype bispecific antibody has been shown to retain effector functions and mediate redirect killing of target cells by cytokine induced killer T cells. In addition, the bispecific antibody demonstrated direct anticancer effects in vitro, as well as in vivo antitumor activity and improved survival in a mouse xenograft model of disseminated leukemia. Immune Pharmaceuticals has identified and prioritized development of highly relevant target combinations in the immuno-oncology space that could have the greatest therapeutic benefits to patients.