Profile: Nektar Therapeutics (NKTR.O)

Nektar Therapeutics (Nektar), incorporated in 1990, is a biopharmaceutical company developing a pipeline of drug candidates that utilize its PEGylation and advanced polymer conjugate technology platforms, which are designed to improve the benefits of drugs for patients. The Company’s product pipeline is comprised of drug candidates across a number of therapeutic areas including oncology, pain, anti-infectives, anti-viral and immunology. Nektar’s research and development activities involve small molecule drugs, peptides and other potential biologic drug candidates. Nektar creates its drug candidates by using its chemistry platform to modify the chemical structure of drugs using polymer conjugates. Nektar’s drug candidates are designed to improve the pharmacokinetics, pharmacodynamics, half-life, bioavailability, metabolism or distribution of drugs and improve the overall benefits and use of a drug for the patient. In December 2008, the Company announced that it closed the divestiture of specific Nektar pulmonary delivery assets, technology, and property to Novartis.

The Company’s most advanced product candidate, Oral NKTR-118, is a peripheral opioid antagonist that is being evaluated for the treatment of opioid-induced constipation (OIC). Its other lead product candidate, NKTR-102, is a cytotoxic topoisomerase I inhibitor that is being evaluated or will be evaluated in four separate Phase II clinical trials for the treatment of multiple cancers, including ovarian, breast, cervical and colorectal. In addition to its internal pipeline, the Company has a number of collaborations and license agreements for its technology with biotechnology and pharmaceutical companies, including Amgen, Schering-Plough, Baxter, UCB and Roche. A total of nine products using its PEGylation technology platform have received regulatory approval in the United States or Europe, and are marketed by its partners. There are also a number of other products in clinical development that use its technology platform.

Nektar has collaboration with Bayer Healthcare LLC to develop BAY41-6551 (NKTR-061, Amikacin Inhale), which is an inhaled solution of amikacin, an aminoglycoside antibiotic. It has another product candidate, NKTR-063 (Inhaled Vancomycin), which uses the same aerosol platform as BAY41-6551. A Phase 1 clinical trial has been completed for NKTR-063 to treat patients with Gram-positive pneumonias. On December 31, 2008, it completed the sale and transfer of certain pulmonary technology rights, certain pulmonary collaboration agreements and approximately 140 of its dedicated pulmonary personnel and operations to Novartis Pharma AG. It retained all of its rights to BAY41-6551 and NKTR-063, certain rights to receive royalties on net sales of the Cipro Inhale (also known as Ciprofloxacin Inhaled Powder or CIP) program with Bayer Schering Pharma AG that it transferred to Novartis as part of the transaction, and it also retained certain intellectual property rights to patents specific to inhaled insulin. In connection with the closing of the transaction, the Company also terminated the Tobramycin Inhalation Powder (TIP) collaboration agreement with Novartis.

Technology Platform

The PEGylation technology is designed to improve the performance of a range of drug classes, including macromolecules (biologics) and small molecules and many classes of drugs and disease areas. PEGylation is a technology platform for the development of therapeutics, such as Roche’s PEGASYS (PEG-interferon alfa-2a) and Amgen’s Neulasta (pegfilgrastim). PEG (polyethylene glycol) is a versatile technology and is a water soluble, amphiphilic, non-toxic, non-immunogenic compound that is safely cleared from the body. Its primary use has been in approved biologic drugs to favorably alter their pharmacokinetic or pharmacodynamic properties. The Company has created the PEGylation technology. Its advanced polymer conjugate technology platform is designed to overcome the limitations of the first generation of the technology platform and allow the platform to be utilized with a range of molecules across many therapeutic areas.

Small Molecule Polymer Conjugates

Its customized approaches with small molecule polymer conjugates allows for the fine-tuning of the physicochemical and pharmacological properties of small molecule oral drugs to potentially increase their therapeutic benefit. In addition, this approach can enable oral administration of subcutaneously-delivered small molecule drugs that have shown low bioavailability when delivered orally. Oral NKTR-118, is a peripheral opioid antagonist that is in the final stages of Phase 2 clinical development.

Small Molecule Pro-Drug Conjugates

The pro-drug polymer conjugation approach can be used to optimize the pharmacokinetics and pharmacodynamics of a small molecule drug to substantially increase both its efficacy and side effect profile. It is using this platform with oncolytics, which typically have sub-optimal half-lives that can limit their therapeutic efficacy. It is using this approach with the two oncolytic candidates in its pipeline, NKTR-102, a PEGylated form of irinotecan in Phase 2 clinical development, and NKTR-105, a PEGylated form of docetaxel in Phase 1 clinical development.

Peptide Large Molecule Polymer Conjugates

The Company’s customized approaches with large molecule polymer conjugates have enabled numerous PEGylated biologics on the market. It is using its advanced polymer conjugation technology-based approach to enable peptides, which are much smaller in size than other biologics, such as proteins and antibody fragments. It is in the early stages of research with a number of peptides that utilize this approach.

Antibody Fragment Conjugates

This approach uses a large molecular weight polyethylene glycol (PEG) conjugated to antibody fragments in order to potentially improve their toxicity profile, extend their half-life and allow for ease of synthesis with the antibody. The specially designed PEG then becomes part of the antibody fragment Fc. Since the antibody fragment is more like a biologic, this conjugation has a branched architecture with either stable or degradable linkage. This approach can be used to reduce antigenicity, reduce glomerular filtration rate, and retain antigen-binding affinity and recognition. There is one approved product on the market that utilizes its technology with an antibody fragment, CIMZIA (certoluzimab pegol), which was developed by its partner UCB Pharma and is approved for the treatment of Crohn’s Disease in the United States.

The Company competes with The Dow Chemical Company, Enzon Pharmaceuticals, Inc., SunBio Corporation, Mountain View Pharmaceuticals, Inc., Neose Technologies, Inc., and NOF Corporation.