Celldex Therapeutics Acquires Kolltan Pharmaceuticals – Expands Antibody and Immuno-Oncology Portfolio

Celldex Therapeutics has entered into a definitive agreement to acquire Kolltan Pharmaceuticals, a clinical-stage company focused on the discovery and development of novel, antibody-based drugs targeting receptor tyrosine kinases (RTKs) and part of a portfolio of companies partly owned by Auven Therapeutics, a private equity firm pursuing an innovative life science investment strategy.

Auven Therapeutics invested in Kolltan Pharmaceuticals in 2009.

Kolltan Pharmaceuticals focuses primarily on oncology and is backed by prominent thought leaders in RTK biology. The company is advancing a new generation of therapeutics in oncology and other diseases, based on seminal discoveries made in the laboratory of Joseph Schlesinger, Ph.D, a Yugoslav-born Israeli-American biochemist and biophysical. Schlesinger, who, in 2001, co-founded Plexxikon (now part of Daichi Sankyo) with Sung-Hou Kim (University of California, Berkeley) is chair of the Pharmacology Department at Yale University School of Medicine, in New Haven, Connecticut. He co-founded Kolltan Pharmaceuticals with Arthur Altschul, Jr. in 2007.

MabPlex
Lonza
ADC Bio
 

The company’s primary focus is to create novel biologic agents that can modulate the function of receptor tyrosine kinases (RTKs). Kolltan has approximately 30 employees, and since its inception in 2008, the Company has raised $75 million in equity funding.

Early pre-clinical data from the company’s drug candidates shows that the novel drug candidates  can help overcome tumor resistance mechanisms associated with current tyrosine kinase inhibitors and seen in patients who have failed other cancer therapies.

Compatible preclinical platform
Celldex believes Kolltan’s clinical candidates and preclinical platform are highly compatible with its own scientific approach and can be developed independently and in combination with their existing product candidates.

“Celldex is committed to driving innovation in oncology to meet the needs of patients and their families,” said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics.

“The acquisition of Kolltan provides Celldex with a truly unique platform of antibodies targeting receptor tyrosine kinases which we believe are highly compatible with our pipeline. We believe this acquisition complements our leadership position in immuno-oncology and enhances our ability to develop targeted therapeutic regimens to dramatically improve patient outcomes,” Marucci added.

KIT, ErbB3 and TAM
“Kolltan’s programs targeting KIT, ErbB3 and TAM receptors potentially address major challenges surrounding tumor resistance mechanisms in cancer biology,” noted Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan Pharmaceuticals.

“Celldex’s leadership and their scientific team played an instrumental role in building the antibody field during their tenure at Medarex and used this expertise to create a leading pipeline in immuno-oncology at Celldex. We firmly believe Celldex is uniquely positioned to advance our antibody portfolio targeting RTKs to improve outcomes for patients and create optimal value for our shareholders,” McMahon.

Portfolio of Drug Candidates
KTN0158 – a humanized monoclonal antibody that is a potent inhibitor of KIT activation in tumor cells and mast cells; currently in a Phase 1 dose escalation study in refractory gastrointestinal stromal tumors or GIST. KTN0158 prevents KIT activation by blocking receptor dimerization. This mechanism may be effective even in tumors harboring the most common resistant mutations to Gleevec® and is unlikely to drive resistance. Preclinical data demonstrate that KIT inhibition in certain immune cells with KTN0158 enhances the activity of checkpoint blockade. This mechanism may also be effective with other immunotherapies, in particular with Celldex’s CD27 agonist, varlilumab.

KTN3379 – a human monoclonal antibody designed to block the activity of ErbB3 (HER3); clinical activity including meaningful responses and stable disease has been observed in a Phase Ib study in cetuximab (Erbitux®) refractory patients in head and neck squamous cell carcinoma and in BRAF-mutant non-small cell lung cancer (NSCLC). The proposed mechanism of action for KTN3379 sets it apart from other drugs in development in this class due to its ability to block both ligand-independent and ligand-dependent ErbB3 signaling by binding to a unique epitope. It also has a favorable pharmacologic profile, including a longer half-life relative to other drug candidates in this class. KTN3379 also has potential to work well in combination with other targeted and cytotoxic therapies to directly kill tumor cells. Tumor cell death and the ensuing release of new tumor antigens could serve as a focus for combination therapy with immuno-oncology approaches, even in refractory patients.

A multi-faceted TAM program – a broad antibody discovery effort underway to generate antibodies that modulate the TAM family of RTKs, comprised of Tyro3, AXL and MerTK, which are expressed on tumor-infiltrating macrophages, dendritic cells and some tumors. Research supports TAMs having broad application and potential across immuno-oncology and immunology. In oncology, as with PD-1 and other checkpoints, TAMs regulate the immune response to cancer. Modulation of TAM pathways may provide additional opportunities to develop drugs to overcome resistance mechanisms, especially when used in combination with either Celldex or external product candidates or with existing approved therapies.

KTN0125
Earlier this year, during the annual meeting of the American Association for Cancer Research (AACR), held in New Orleans, Louisiana, April 16-20, 2016, positive preclinical findings for KTN0125, an anti-ALK antibody conjugated to a thienoindole cytotoxic agent (TEI), were discussed in an oral presentation. At the time of the AACR presentation, Kolltan’s McMahon noted that “the preclinical data presented provides a compelling rationale to move our ALK-ADC program into development for the treatment of pediatric neuroblastoma and other ALK-expressing childhood cancers.”

KTN0182A
In 2015 the company presented preclinical data from KTN0182A, Kolltan’s anti-KIT antibody drug conjugate development program at the 11th Annual PEGS – The Essential Protein Engineering Summit, held in 2015 in Boston, Massachusetts.  The anti-KIT, pyrrolobenzodiazepine (PBD)-containing ADC demonstrated potent antitumor activity in vitro and in vivo against a broad range of tumor types.

KTN0182A is comprised of the KTN0158 humanized immunoglobulin G1 kappa (IgG1ĸ) monoclonal antibody that specifically binds the membrane-proximal D4 domain of KIT and inhibits dimerization of the receptor, conjugated to the SG3227 pyrrolo[2,1-c][1,4]benzodiazepine anti tumor antibiotic that binds in the minor groove of DNA to cross-link DNA strands and produce highly lethal lesions.

The antitumor antibiotic SG3227 contains a cathepsin-cleavable valine/alanine linker attached at the N10 site of the PBD dimer. Random conjugation occurs via an iodoacetamide functional group in the linker at cysteine residues of the antibody following KTN0158 reduction, with an average drug to antibody ratio (DAR) of approximately 2. [1]

Based on the preliminary data researchers noted that KTN0182A has potential as a therapy for numerous KIT-positive malignancies, both as a primary therapy and as a way to overcome acquired resistance following small molecule kinase inhibitor treatment.

Agreement
Upon closing of the acquisition of Kolltan, Celldex’s clinical pipeline will include seven drug candidates including therapeutic antibodies, antibody-drug conjugates (ADCs) and immune system modulators, which are being tested in a range of difficult-to-treat indications in oncology. This broad pipeline allows for novel combination approaches, several of which are already under study. In addition, Celldex would have two active preclinical programs.

Under the terms of the agreement, Celldex will acquire Kolltan in a stock-for-stock transaction, in which the upfront payment represents an equity value of approximately U.S. $ 62.5 million. In addition, Kolltan shareholders are eligible to receive additional payments of up to U.S. $ 172.5 million upon the completion of specific development, regulatory and commercial milestones. The transaction, which is subject to the receipt of Kolltan stockholder approval and other customary closing conditions, is expected to be completed by year-end.

The Boards of Directors of both Celldex and Kolltan have unanimously approved the transaction, and Kolltan’s Directors have unanimously recommended that their stockholders approve the transaction.