ProNAi Therapeutics Inc.
This article was originally published in Start Up
Executive Summary
The potentially profitable idea in ProNAi's portfolio is an approach the drug development community overlooked--taking direct aim at a diseased cell's DNA in order to suppress a disease pathway. ProNAi will use nucleic acid interfering technology (DNAi) to develop drugs across a broad spectrum of genetic diseases, but it intends to file its first INDs for prostate cancer and non-Hodgkin's lymphoma.
DNAi drugs for cancer
Southwest Michigan Innovation Center
4717 Campus Drive, Suite 1100
Kalamazoo, MI 49008
Phone: (269) 372-3289
Fax: (269) 544-1079
Web Site: www.pronai.com
Contact: Robert Forgey, Chief Operating Officer
Industry Segment: Biotechnology; Pharmaceuticals
Business: Nucleic Acid inhibitor (NAi) drug development
Founded: 2004
Founders: Neal Goodwin, PhD, CSO; Robert Forgey, COO; Mina Sooch (Apjohn Ventures); Donald Parfet (Apjohn Ventures)
Employees: 5
Financing to Date: $4.25 million
Investors: Grand Angels; Biosciences Research Commercialization Center; Apjohn Ventures; Michigan Technology Tri-Corridor; Individual investors
Board of Directors: Donald Parfet; Mina Sooch; Michael E. Pape, PhD (formerly Esperion Therapeutics Inc.); Neal Goodwin
Scientific Advisory Board: Neal Goodwin; Terry Magnuson PhD (University of North
Carolina); David Olson, PhD (PanCel Corp.); John Schimenti, PhD (Cornell University); CraigWebb, PhD (Van Andel Institute); Patrick McGovern, PhD (formerly Pfizer Corp.); Ayad Al-Katib, MD (Wayne State University); Mace Rothenberg MD (Vanderbilt University)
The potentially profitable idea in ProNAi Therapeutics Inc. 's portfolio is an approach the drug development community overlooked--taking direct aim at a diseased cell's DNA in order to suppress a disease pathway. Suppressing expression of a disease-causing gene at its source (a nucleic acid sequence) may seem an obvious approach in the age of biotechnology; however, ProNAi says it is the only company employing it to develop therapeutics.
A bit of history may explain why other companies have not attempted to capitalize on targeting DNA directly. In the 1980s, the triple helix approach (the creation of a third nucleic acid strand that would attach to and silence a DNA sequence) encountered several obstacles to becoming a viable therapeutic entity. Among them were the inability of oligonucleiotides (nucleotides strung together by a polymer) to recognize and stick to their target sequences and questions about the accessibility of the target itself, DNA.
According to Robert Forgey, ProNAi's COO, at the time, the flourishing field of antisense technology usurped the triple helix approach. Later successes with ribozymes and RNA interference (RNAi) contributed to its obscurity.
Forgey is careful to distinguish ProNAi's platform technology from the triple helices of past decades, as well as RNAi and antisense. RNAi and antisense intervene with messenger RNA's ability to transmit the protein coded in a gene sequence to the protein-producing machinery of the cell. ProNAi says it is unique in developing a therapeutic platform directed at the original source of the coded protein using nucleic acid interfering technology (DNAi) or sequence-specific therapeutics.
ProNAi was formed by Neal Goodwin, PhD, CSO, and Robert Forgey, COO, both formerly with Pharmacia. The two men felt nucleic acid research presented a huge opportunity and they left Pharmacia to form a company called Phenome Systems. Mina Sooch and Donald Parfet formed their own nucleic acid company, Sensagene, based on research conducted at Wayne State University . Both companies made significant headway in discovering and developing a new class of nucleic acid based therapeutics. In 2004, Phenome Systems and Sensagene pooled their resources and merged to form ProNAi Therapeutics.
ProNAi, has eight patent applications pending and expects to receive them in late 2005 or early 2006. The company already possesses one issued patent that came in with Sensagene for a modified oligoribonucleotide and methods of using it to prevent transcription of a specific oncogenic pathway known as RAS. Activation of the RAS cellular pathway prevents the cell from undergoing apoptosis or cell death and creates a cell that is immortal.
ProNAi is proposing to silence pertinent disease pathways, such as RAS, with DNAi technology--a potent therapeutic approach not only for oncology but other diseases caused by pathological gene expression. The company's long-term goals include developing DNAi therapies across the spectrum of genetic diseases.
Its short-term focus, according to Forgey, is proof of principle. ProNAi is currently testing nucleic acid interfering-based drug candidates in animals, more specifically animals with human tumor grafts. The company states that its most advanced lead compound, PNT100, is showing promise in several types of cancer and has demonstrated in vivo efficacy in these animal models. Forgey says ProNAi intends to file its first investigational new drug applications for prostate cancer and non-Hodgkin's lymphoma (NHL) in 2006.
Prostate cancer is the growth of malignant cells in the prostate, a walnut-size gland located just below the bladder in men. Men have a lifetime chance of between 1-10 and 1-13 of developing the disease making prostate cancer one of the most common malignancies. While not every diagnosis is serious (there are many subtypes), prostate cancer is still a leading cause of cancer-related death in men worldwide.
There are no effective chemotherapies for metastatic prostate cancer, the most advanced form of the disease. Treatment when necessary consists of surgery, radiation or brachytherapy (the placement of radiation near the tumor site). A safe drug capable of stopping or slowing the rate of tumor growth or capable of destroying it outright would significantly improve the quality of life for prostate cancer patients and potentially increase chances of survival.
While ProNAi sees virtually no competition relative to using DNAi as a therapeutic approach, developments in the field of oncology are abundant. The list of drugs in development for prostate cancer is long (PhRMA's report on New Medicines in Cancer Development, May 17, 2005, places the number at 50). Three candidates are vaccines with Dendreon Corp. 's Provenge already in Phase III.
NHL originates in lymphoma cells. According to the American Cancer Society, there will be an estimated 56,390 new cases of NHL this year, and the number of related deaths in 2005 is expected to be 19,200. A significant number of patients with the fast-growing or aggressive form of NHL are treated with intensive chemotherapy and can be cured. A continuous rate of relapse is associated with advanced stages of indolent (slow growing) NHL even though the disease is initially responsive to radiation therapy and chemotherapy.
Immunotherapeutics for NHL are having an impact on both patients and the market. Treatment outcomes for patients with NHL recently improved with the introduction of two MAbs attached to radioisotopes. GlaxoSmithKline PLC 's tositumomab (Bexxar) (licensed from Corixa Corp. via Coulter Pharmaceutical Inc. [See Deal]) and Biogen Idec Inc.'s ibritumomab (Zevalin) target NHL cells and deliver the radiation directly to the site(s) of disease. The introduction of these therapies has improved prognosis of indolent lymphoma patients by extending progression-free survival. Clinical trials were conducted in patients with no treatment alternatives and the therapy is being introduced in treatment naïve patients or first line in investigational trials.
In 2004, sales of Zevalin generated US revenues of $18.7 million. Schering AG has licensed the product for the rest of the world. [See Deal] Those sales reached $4.3 million the same year. Corixa reported Bexxar sales of $2.5 million in the third quarter of 2004, far short of the $20 million sales goal they had originally set. GSK acquired Corixa in early 2005. [See Deal].
ProNAi estimates its potential value in the NHL and prostate cancer markets at $2-plus billion. Its estimates are based on the use of their therapy reaching the same level as chemotherapy and radiation for NHL and other first-line strategies such as surgery for treating metastatic prostate cancer. The road is long for ProNAi but Forgey believes this type of technology holds a lot of promise for changing views on how to treat disease. He acknowledges that one of the major limiting factors to the clinical development of nucleic acid treatments is actually transporting genetic drugs to the affected cells.
Delivery systems are needed to compact nucleic acids into small structures that can be taken up by cells, to protect genetic materials from enzymatic degradation during extra- and intracellular transport, to neutralize the negative surface charge of nucleic acids, and to provide a means of targeting the drug to the specific site of disease and region within the cell.
ProNAi has a licensing agreement in place with an undisclosed partner to manufacture its therapeutics. The company is pursing an additional agreement for a liposomal delivery package to encase its therapeutic entities. Liposomes, microscopic lipid spheres that can be used to encapsulate and deliver medications to areas of disease within the body, have already proved effective for delivering some drugs and reducing the toxicities of chemotherapy. Forgey describes the liposomal technology licensed by ProAi as something newer than the historic liposome.
He also explains that ProNAi's drug candidates will have additional advantages over other therapies currently in development: they will have a shorter drug development cycle (since the genome is their guide) and they should be cost-effective to produce, especially compared to antisense and RNAi approaches.
ProNAi's Series A round raised $2.5 million, followed by a $1.75 million convertible note financing. Forgey says that ProNAi will wait until 2006 before deciding whether to pursue venture capital or corporate partnerships before taking the technology to the clinical development stage.—Barbara Nasto