Emerging Firms Highlighted at Roth Meeting

T-cell therapy, oxidative stress, lipidomics, and parthenogenesis were some of the concepts discussed at the “20th Annual OC Growth Stock Conference” presented by Roth Capital Partners recently.

Therapeutic antibody sales have increased significantly over the last decade. The market is currently pegged at $30 billion per year with $25 billion of that having an oncology focus, according to Christian Itin, Ph.D., president and CEO of Micromet, which is developing antibodies for the treatment of cancer, inflammation, and autoimmune diseases.

Three of Micromet’s antibodies are in clinical development. MT103, the most advanced antibody in the company’s pipeline, and developed using the BiTE® antibody technology platform, is in a Phase II trial for the treatment of acute lymphoblastic leukemia and in a Phase I trial for non-Hodgkin’s lymphoma.

BiTE antibodies represent “a new class of antibodies that activate a patient’s own cytotoxic T cells to eliminate cancer cells,” Dr. Itin said. Micromet is developing MT103 in collaboration with MedImmune, now part of AstraZeneca. “T cells are key policemen for tumor cells, and BiTE antibodies help to find them,” Dr. Itin explained.

Elevating oxidative stress selectively kills cancer cells, especially melanomas, by inducing apoptosis, noted Safi Bahcall, Ph.D., president and CEO of Synta Pharmaceuticals.

Synta has a chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. Synta has a partnership with GlaxoSmithKline for the joint development and commercialization of its lead investigational drug candidate, elesclomol, which is in a Phase III trial for the treatment of metastatic melanoma.

“Melanoma is an area in which no drug has been successful,” Dr. Bahcall said. “Our lead drug, which demonstrated a 42 percent reduction in metastatic melanoma, gives us an opportunity to define a standard of care.”

Ziopharm Oncology applies new insights from molecular and cancer biology in its efforts to understand the efficacy and safety limitations of approved and developmental cancer therapies and identify proprietary and related molecules for better patient treatment, according to its CEO, Jonathan Lewis.

The company has three products in clinical development. Darinaparsin (ZIO-101), which is based on an ancient Chinese remedy that uses an organic form of arsenic to treat cancer, is in Phase II trials for myeloma, primary liver cancer, and diverse hematological malignancies. A Phase I trial that involves oral administration is under way.

The company’s second drug, palifosfamide (ZIO-201), is in late Phase II trials in patients with advanced sarcoma and various advanced cancers. A Phase I/II sarcoma combination trial is also ongoing. Finally indibulin (ZIO-301), a low neurotoxicity drug designed to stop cell division and migration, is currently in a late Phase I trial in Europe and the U.S. as well as a recently initiated Phase I/II combination trial.

SGX Pharmaceuticals uses structural information from proteins to advance cancer therapeutics, explained CEO Mike Grey. “Validated targets include mutations and chromosomal abnormalities that result in tumors. Mutations that affect kinases are found in many types of cancer,” he added.

The SGX oncology pipeline includes drug candidates from the company’s FAST™ drug discovery platform, such as SGX523, a cMET kinase inhibitor currently in Phase I studies, BCR-ABL inhibitors being developed by SGX in partnership with Novartis, and JAK2 inhibitors.

The FAST platform is a target-to-structure platform focusing on low molecular weight fragments as starting points that are optimized to create high-affinity compounds broadly applicable against a wide range of targets with the objective being highly potent, highly selective molecules, Grey concluded.

Multiple Uses for Lipids

“Twenty or thirty years ago lipids were not on the radar screen in terms of bioactivity,” said Scott Pancoast, CEO of Lpath, a company that develops lipidomics-based therapeutics, an emerging field of medical science whereby bioactive signaling lipids are targeted for treating important human diseases. Most of the company’s 26 issued or pending patents were developed in-house based on lipid-signaling research by the company’s founder, Roger Sabbadini, Ph.D.

Lpath’s lead product candidate, Asonep™ (the systemic formulation of Sphingomab™), which received FDA approval in January to enter Phase I testing, is a mAb against sphingosine-1-phosphate, a validated cancer target. The company’s second product candidate, iSONEP™ (the ocular formulation of Sphingomab), has demonstrated effectiveness against macular degeneration and may have potential for use in glaucoma therapy because of its antifibrotic mechanisms.

Lpathomab™, a third product candidate, is a mAb against lysophosphatidic acid, a key bioactive lipid that has long been recognized as a significant promoter of cancer-cell growth and metastasis in a broad range of tumor types and a significant contributor to neuropathic pain.

Metabasis is applying its technologies and scientific expertise to the liver and liver pathways, reported Paul Laikind, president and CEO. The company’s metabolic products are aimed at diabetes and hyperlipidemia.

HepDirect® guides drugs to the liver, resulting in increased levels of the pharmacologically active form of the drug in the liver and decreased levels in nonliver tissues, Laikind said. The company’s NuMimetic™ technology is used to discover molecules that bind effectively and specifically to nucleotide binding sites residing in certain enzymes.

Antimicrobial Technology

Oculus Innovative Sciences uses its Microcyn® technology platform to help prevent and treat infections in chronic and acute wounds.

The solutions derived from the Microcyn technology platform demonstrated in a variety of research and investigational studies the ability to treat a wide range of pathogens including antibiotic-resistant strains of bacteria, viruses, fungi, and spores, according to Hoji Ajimi, founder and CEO of Oculus. The technology also demonstrated wound healing in chronic and acute wounds in clinical investigational studies.

“This is not just another antimicrobial technology,” Ajimi said. “It eradicates infection, oxygenating tissue and increasing vasodilation, and inhibits histamine release to promote healing. It has been commercialized and used on approximately one million patients who faced amputation because of sepsis in Mexico, India, and Europe.”

Stem Cells

“We convert the miracle of birth to therapeutics,” explained Zami Aberman, CEO of Pluristem Therapeutics. The company’s products are derived from mesenchymal stromal cells (MSCs) obtained from the placenta rather than embryonic stem cells. The MSCs are then expanded in the company’s PluriX™ 3-D bioreactor, which mimics the natural environment of bone marrow.

Pluristem’s first planned product, PLX-I, targets a $3 billion annual market and is intended to resolve the global shortfall of matched tissue for bone marrow transplantation, according to Aberman.

The company’s PLacental eXpanded cells are designed to accelerate angiogenesis and increase blood flow to the limbs to help patients afflicted with peripheral artery disease with critical limb ischemia.

International Stem Cell’s (ISCO) parthogenesis technology results in the creation of pluripotent, human stem-cell lines from unfertilized human eggs, according to Kenneth Aldrich, chairman and CEO.

ISCO scientists also created a parthenogenetic homozygous stem-cell line that can be a source of therapeutic cells that will not be immune rejected after transplantation into individuals of differing sexes, ages, and racial groups, Aldrich noted.

These advancements offer the potential to create the first true stem-cell bank and address ethical issues by eliminating the need to use or destroy fertilized embryos, according to Aldrich. ISCO also produces and markets specialized cells and growth media worldwide for therapeutic research through its Lifeline Cell Technology subsidiary.

“The goal is not to own a therapeutic procedure or a medical device,” said Aldrich. “Rather, we want to create a business model of providing research kits of cells and media without designing clinical trials for a narrow application.”