Kolltan announces presentation of data from KTN0158 preclinical study in mast cell tumors at ESMO 2015

Kolltan Pharmaceuticals, Inc. today announced the presentation of data from a preclinical study evaluating KTN0158 in dogs with spontaneous mast cell tumors. KTN0158 is a proprietary, humanized anti-KIT IgG1 monoclonal antibody drug candidate being developed as a potential therapy for cancer and mast cell-related diseases. Overall, substantial tumor shrinkage was observed during this study when KTN0158 was administered to dogs with spontaneous mast cell tumors, also known as mastocytomas. In addition, tumor shrinkage was observed at all dosing levels after one or two doses and in tumors with and without activating KIT mutations. KIT is a receptor tyrosine kinase (RTK) known to drive the growth of certain tumor types and is associated with activating mutations in both dog mastocytomas and human tumors such as gastrointestinal stromal tumors (GIST), melanoma and leukemias. Based on these results, and favorable results from a preclinical toxicology study in non-human primates, Kolltan plans to file an investigational new drug application (IND) for KTN0158 with the FDA in the fourth quarter of 2015.

The preclinical results were presented today in a poster titled, "KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Antitumor Activity in Dogs with Mast Cell Tumors" (Poster #209, Abstract #202, Translational Research on Monday, September 28, 4:45 PM - 6:45 PM CEST, Location: C Hall at the European Cancer Conference 2015). The conference is being hosted by the European Society for Medical Oncology (ESMO) and being held in Vienna, Austria between September 25-29, 2015.

"We are excited about the preclinical data presented today and generated to date which support the evaluation of KTN0158 in the treatment of KIT-expressing tumors when wild-type or mutant KIT is expressed. We believe that KTN0158's potential to treat both wild-type and mutant KIT-expressing tumors is related to its high potency and unique binding features, which block the dimerization and signaling of the KIT receptor," said Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan. "As a result, we believe that KTN0158 has the potential to be superior or complementary to small-molecule approaches to block the enzymatic function of this RTK. We are rapidly moving this program forward and are on track to file an IND this year in oncology. We plan to evaluate KTN0158 as a monotherapy in human cancers, such as GIST and other KIT-dependent tumors, and continue to explore it as a potential combination anti-cancer therapy.

"The IND for KTN0158 is supported by the favorable results from the nonclinical toxicology studies performed to date along with the activity of this antibody that may be due to the novel binding and blocking features of KTN0158, which has no agonist activity in vitro. Our studies further support evaluation of this product candidate to modulate mast cells, where KIT is expressed and active, in addition to blocking KIT as a tumor driver. We have generated preclinical data, and will be presenting new data at other scientific meetings, to support the use of KTN0158 to block mast cells, which in turn we expect will support applications in oncology, neurofibromatosis 1, and other diseases," said Theresa LaVallee, Ph.D., Senior Vice President, Translational Medicine and Product Development at Kolltan.

The open-label, dose-escalating study of KTN0158 included 13 dogs with measurable spontaneous mast cell tumors (MCT), of which 12 were evaluable for efficacy, and was conducted by Dr. Cheryl London at The Ohio State University. Three dose levels and two schedules were tested. KTN0158 was given at 10 or 30 mg/kg as a single dose or given as two doses of 1 or 10 mg/kg three weeks apart. As part of the study, tumor biopsies and blood samples for PK and PD analysis were collected. The study also incorporated weekly assessments including physical examination and standard laboratory tests (serum chemistries, hematology profiles, and urinalyses) for toxicities and response. Antitumor efficacy was based on objective tumor assessments made according to established RECIST criteria for solid tumors in dogs. Adverse events (AEs) were recorded and graded according to VCOG-CTCAE v.1.1 criteria for AEs in dogs.

The presentation includes the following results and data:

• Clinical benefit of KTN0158 was observed in all dogs with MCTs at all dosing levels and in dogs with both wild-type and mutant expressing tumors:
  • -Five animals showed partial responses and seven animals had stable disease; and

    -Histopathology after study completion showed a lack of neoplastic cells in primary tumors and/or lymph node samples from a total of four dogs.

• Reversible hematologic and biochemical effects were observed in dogs receiving either a 10 or 30 mg/kg/dose of KTN0158 with the maximum tolerated dose established at 10 mg/kg.

• IND enabling toxicology studies in non-human primates revealed no significant findings, including hematologic effects, after repeat dosing of KTN0158, with a no observed adverse event level (NOAEL) of 75 mg/kg, the highest dose tested.