9/6/2011
Jennerex’s Virus-Based Drug Targets & Infects Tumors
Jennerex, Inc. recently announced the publication of clinical data on its lead product JX-594. For the first time in humans, an oncolytic virus was shown to reproducibly infect, replicate, and express transgene products within cancer tissue after intravenous infusion. Normal tissues were not significantly affected clinically, underscoring the designed selectivity of JX594 for malignant tissue and safety of the product.
“Our platform technology opens up the possibility of selectively expressing multiple transgene products with complementary mechanisms of action at high concentration in tumors systemically. This is a first in medical history,” said David Kirn, MD, President and CEO of Jennerex. “We believe it will take truly innovative, multi-mechanistic approaches to significantly prolong survival, and to potentially cure patients with metastatic solid tumors. JX-594, with its ability to reach tumors systemically after IV infusion, coupled with its three complementary mechanisms of action, represents a bold new approach to the treatment of metastatic cancers.”
“We look forward to working with our partners on the clinical development of JX-594 in liver, colorectal, and other cancer types,” added Dr. Kirn. We’re particularly excited about the TRAVERSE trial, a global, randomized, controlled Phase IIb clinical trial of JX-594 in patients with hepatocellular carcinoma (liver cancer) having failed sorafenib (Nexavar) treatment, which we plan to initiate this year.”
JX-594 replication and engineered transgene expression within solid tumors was evaluated on a Phase I dose-escalation trial of intravenous infusion of JX-594. Twenty-three patients with advanced, treatment-refractory solid tumors were enrolled in one of six cohorts. Safety, antitumor activity, and pharmacokinetic parameters were also evaluated. JX-594 was generally well-tolerated, and dose escalation proceeded without dose-limiting toxicities. The most common treatment-related adverse events consisted of Grade 1-2 flu-like symptoms lasting up to 24 hours. Cancer-selective and dose-related JX-594 delivery and replication in tumors were demonstrated in biopsies obtained 8 to 10 days following infusion. In patients receiving higher doses whose tumor biopsies were evaluable for analysis, 87% exhibited JX-594 positivity, whereas JX-594 was not detected in biopsies collected from patients receiving lower doses.
JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: 1) the lysis of cancer cells through viral replication, 2) the reduction of the blood supply to tumors through vascular targeting and destruction, and 3) the stimulation of the body’s immune response against cancer cells, ie, active immunotherapy. Phase I and Phase II clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients (over 100 treated to date). Objective tumor responses have been demonstrated in a variety of cancers, including liver, colon, kidney, lung, and melanoma. JX-594 has a favorable safety profile with predictable and generally mild side effects that typically include flu-like symptoms that resolve in 48 to 72 hours.
The vaccinia poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells. JX-594 was engineered to enhance this natural safety and cancer-selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the GM-CSF protein. GM-CSF complements the cancer cell lysis work of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown, and an anti-tumoral immune attack.
Transgene, a biopharmaceutical company specialized in the development of immunotherapeutic products, holds an exclusive license to develop and commercialize JX-594 in
Jennerex, Inc. is a clinical-stage biotherapeutics company focused on the development and commercialization of first-in-class, breakthrough targeted oncolytic products for cancer. The company’s lead product JX-594 is currently in two Phase II clinical trials in patients with primary liver cancer, an international, randomized, Phase II clinical trial, and a Phase II study of JX-594 in combination with sorafenib. Published studies designed to establish optimal dose levels and the safety profile of JX-594 have shown its ability to selectively target and cause destruction of a variety of common cancer types. JX-594 and other product candidates under development are designed to attack cancer tumors through three diverse mechanisms of action: the lysis of cancer cells through viral replication, the ablation of the blood supply to tumors through vascular targeting and destruction, and the stimulation of the body’s immune response against the cancer. Jennerex is headquartered in
Marina Biotech Granted US Patent Related to Nucleic Acid-Peptide Drug Delivery Platform
Marina Biotech, Inc. recently announced the US Patent and Trademark Office (USPTO) has issued a Notice of Allowance for patent application US 11/955,207 with claims that cover a library of over 1×10(15) novel peptides. The patent application is part of the company’s proprietary Trp Cage Library patent portfolio. This allowance strengthens the company’s nucleic acid-peptide drug delivery platform, and further expands the company’s patent protection for its comprehensive set of nucleic acid delivery technologies, which also include DiLA2, SMARTICLES, and the tkRNAi system.
“A primary advantage of this patented peptide library is the ability to rapidly screen and identify novel peptides that exhibit cell-specific targeting characteristics for directed delivery of nucleic acid therapeutics,” said Barry Polisky, PhD, Chief Scientific Officer of Marina Biotech. “Delivery remains a significant challenge in the nucleic acid therapeutic space, and peptides with high affinity and specificity are expected to be a fundamental component to developing delivery approaches to a wide spectrum of tissues and cell types. In addition, the library may also be exploited to screen for peptides that function as specific antagonists, agonists, or generally exhibit drug-like properties.”
The company’s proprietary Trp Cage Phage Display Library is the subject of issued patents, US Patent No. 7,329,725; US Patent No. 7,704,953, and US Patent No. 7,772,189. The Trp Cage motif is highly structured allowing for the identification of peptides with high binding affinity for specific cell or tissue types, and avoids the limitations of low affinity and specificity often associated with linear peptide libraries. This technology is directly applicable to the company’s DiLA2 and SMARTICLES delivery platforms as peptides are readily conjugated to the components of these delivery platforms. Peptides capable of directed delivery are expected to further improve the delivery efficiency of the company’s UNA and CRN substituted nucleic acid constructs, which have demonstrated in vivo activity and efficacy against targets in both normal/healthy and disease models, respectively.
A Notice of Allowance confirms the substantive examination of a patent application and will result in a final issuance of a
Marina Biotech is a biotechnology company focused on the development and commercialization of RNA interference-(RNAi) and RNA-based therapeutics. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs – in bladder cancer and malignant ascites. Marina Biotech entered into an exclusive agreement with Debiopharm Group for the development and commercialization of the bladder cancer program. The company’s goal is to improve human health through the development of RNAi and RNA-based compounds and drug delivery technologies that together provide superior therapeutic options for patients.
Unilife Develops
Unilife Corporation recently announced the development of a unique proprietary range of auto-injectors for the self-administration of injectable drugs by patients outside of healthcare facilities. Developed for use in conjunction with Unifill prefilled syringes, Unifill Auto-Injectors are compact in size and enable patients to inject a fixed dose of medication with the simple push of a button, without ever seeing the needle. Unlike conventional auto-injector technologies that are used with standard prefilled syringes, the incorporation of the Unifill syringe with its integrated safety features give Unifill Auto-Injectors several significant market advantages, including a small diameter, a true end-of-dose indicator, and automatic retraction of the needle from the skin after completion of the injection.
Unilife has developed its Unifill Auto-Injectors in single-use disposable and re-usable configurations for use across a wide spectrum of therapeutic drug classes. The Unifill self-injection systems can be customized to support a range of drug viscosities, patient dexterity, and visual acuity requirements. Injectable drugs are increasingly supplied in both prefilled syringe and auto-injector formats across a multitude of therapeutic classes. The availability of the Unifill syringe, either in a stand-alone format or supplied together with the Unifill Auto-Injector, can enable pharmaceutical companies to standardize their device platforms under the Unifill technology.
“Unifill Auto-Injectors represent a breakthrough technology within the billion-dollar market for self-injection systems,” said Mr. Alan Shortall, CEO of Unilife. “Existing auto-injectors in the market use conventional prefilled syringes and can be bulky in size, as they are required to undertake several tasks, including the automatic insertion of the needle into the body, the injection of the dose, and the subsequent extension of a shield over the needle. Unilife’s auto-injector uses the Unifill prefilled syringe, which automatically retracts the needle back into the barrel upon full dose delivery. Consequently, our Unifill Auto-Injectors utilize fewer components, are more reliable, and are compact in size for portability, easy handling and convenient disposal.”
The audible click and tactile feedback, which signals the activation of the safety mechanism and the automatic retraction of the needle from the body, also gives the Unifill Auto-Injectors a true end-of-dose indicator. In addition, making the needle virtually invisible to the patient is another important feature that garners significant user acceptance and preference for our auto-injector.
“Conventional auto-injector technologies can cause some confusion among patients, as it can be difficult to determine just when the full dose has been delivered. For Unifill Auto-Injectors, once a patient hears the audible-tactile indication signaling the activation of the safety mechanism, they know the dose has been fully administered, and the device can be safely taken away from the body. This true end-of-dose indicator represents a unique competitive advantage for our auto-injectors that addresses a key unmet need given the importance of accurately administering a full dose of medication to optimize patient compliance with therapy regimes,” added Mr. Shortall.
“Unilife has developed its proprietary platform of Unifill Auto-Injectors in direct response to the unmet needs of pharmaceutical companies and patients,” explained Dr. Ramin Mojdeh, COO of Unilife. “We are excited by the potential of our Unifill Auto-Injectors to improve patient care, optimize therapy compliance, and generate powerful brand differentiation for their injectable drugs. And we look forward to advancing discussions regarding our Unifill Auto-Injectors with a number of pharmaceutical companies. Due to the increasing number of prefilled drugs being supplied in an auto-injector format, we expect that approximately 20% of all Unifill syringes could be supplied in conjunction with a Unifill Auto-Injector. The development of this range of Unifill Auto-Injectors will significantly increase our ability to penetrate a number of therapeutic markets where patient self-administration is becoming increasingly common.”
Industry reports project the market for auto-injectors to grow at a CAGR of 17.8% between 2010 and 2015, with demand being driven by the development and commercial launch of biologics, biosimilars, and other drugs suitable for patient self-injection as well as the enforcement of laws in the US, Europe, and other emerging markets seeking to prevent needlestick injuries. Therapeutic drug classes where auto-injectors can help improve patient care include multiple sclerosis, allergies, anemia, cancer, psoriasis, rheumatoid arthritis, HIV-AIDS, osteoporosis, fertility, and human growth hormone treatments.
Oxford BioTherapeutics Licenses Lonza’s GS Gene Expression System
Oxford BioTherapeutics Ltd and Lonza recently announced a non-exclusive license agreement providing OBT with access to Lonza’s GS Gene Expression System. The agreement covers the research, development, and commercial use of the GS System by OBT and contains standard payments and license fees that have not been disclosed. Licensing of the GS Gene Expression System expands OBT’s access to world-class technologies for its maturing pipeline of therapeutic antibodies in oncology, and demonstrates its commitment to strengthening both antibody production and preclinical capabilities.
“We are delighted to have access to Lonza’s GS Gene Expression System as an addition to our technology portfolio,” said Tom Boone, who recently joined OBT as Senior Vice President, Protein Sciences following 28 years at Amgen. “The speed and ease of use of the GS System will aid the rapid selection of high-producing cell lines and accelerate the production and development of our most promising anticancer agents.”
“We are proud to have our GS Gene Expression System contribute to Oxford BioTherapeutics innovation in cancer research,” said Janet White, Head of Development Services. “We look forward to supporting OBT’s efforts to expand and develop its pipeline of promising new oncology drugs.”
The GS Gene Expression System, which is owned and licensed by Lonza, is used for the production of therapeutic recombinant proteins and monoclonal antibodies. Nearly 100 biotechnology and pharmaceutical companies and over 75 academic laboratories worldwide are successfully using the GS Gene Expression System, which has established itself as the industry standard. This system is characterized by its speed and ease of use. In addition, the higher yielding cell lines provide cost-efficient production of therapeutic proteins.
The Oxford Genome Anatomy Project (OGAP) database represents the world’s largest proprietary collection of disease-associated proteins. OGAP oncology contains proteomic data on 5,000 cancer membrane proteins combined with their genomic and clinical information derived from human blood and cancer tissue studies. OGAP contains proprietary target information on three quarters of the entire human proteome. Over 1 million human protein fragments have been sequenced in OGAP in 50 different human tissues representing 60 diseases, including 25 forms of cancer covering 17,000 different genes and over three quarters of all human proteins and genetic variants in over 8 million SNPs and haplotypes.
MonoSol Rx Announces Second PharmFilm Product
MonoSol Rx, LLC recently announced it plans to develop a second oral film product for the treatment of attention-deficit hyperactivity disorder (ADHD) with its partner KemPharm, Inc. KP415, which was recently discovered by KemPharm, is a novel prodrug of methylphenidate, a commonly used medication for the treatment of ADHD.
The companies plan to co-develop the oral film dosage form of KP415 under a previously established exclusive technology and manufacturing partnership, which also currently includes KP106, a pro-drug of d-amphetamine. If approved, these drug candidates will be the first oral film products for the treatment of ADHD, which consist primarily of a pediatric patient population.
“The addition of KP415 to our partnership with KemPharm provides us with a portfolio of highly differentiated products for treating ADHD,” said A. Mark Schobel, Co-President and CEO of MonoSol Rx. “We believe delivery of KP415 and KP106, using our patented PharmFilm technology, significantly improves the convenience with which these novel molecules, which represent two major classes of drugs used to treat ADHD, can be dosed. This may improve patient compliance and therapeutic outcomes. We look forward to working closely with KemPharm to advance these programs and to commercializing the first ADHD treatments using oral film drug delivery.”
“We share our enthusiasm about the discovery of KP415 with our partners at MonoSol Rx,” added Travis C. Mickle, PhD, President and CEO of KemPharm. “Along with KP106, our diversified, next-generation ADHD portfolio has the potential to change the way this disorder is treated by creating novel prodrugs with the potential to improve upon existing therapies in clinically meaningful ways.”
Under terms of the agreement, the companies will co-develop and commercialize KemPharm’s KP415 and KP106 utilizing MonoSol Rx’s PharmFilm delivery platform. MonoSol Rx will be the exclusive manufacturer and be eligible for development milestone payments.
Cyclacel Announces Phase II Trial of Sapacitabine
Cyclacel Pharmaceuticals, Inc. recently announced that the first patient has been dosed in an investigator-initiated, translational, Phase II clinical study at The University of Texas MD Anderson Cancer Center. The objective of the study is to learn if oral sapacitabine capsules given in combination with two standard injectable drugs, cyclophosphamide and rituximab, or the SCR regimen, can help control chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in up to 40 relapsed patients with leukemia cells containing the 11q22-23 chromosome deletion. Deletion at chromosome 11q22-23 is associated with deletion of the Ataxia Telangiectasia Mutated (ATM) gene, an important element of the homologous recombination DNA repair (HRR) pathway. Previous findings show that cells with HRR pathway defects are particularly sensitive to sapacitabine. Sapacitabine may therefore be of particular benefit to patients with ATM-defective blood cancers.
“As gene-based, personalized medicine approaches have in certain cases been developed and approved faster than traditional methods, we are encouraged by the prospect of tailoring treatment with sapacitabine to the genetic profile of an individual’s cancer cells,” said Spiro Rombotis, President and CEO of Cyclacel. “We have collaborated with Dr. Wierda, Dr. Plunkett, and their teams for several years to study sapacitabine’s effects on the DNA repair pathway. We thus welcome the opportunity to explore the hypothesis that the presence of 11q22-23 deletion may translate into clinical benefit for patients treated with the sapacitabine-based SCR regimen, while doing so in a fiscally responsible and collaborative manner. We look forward to the eventual outcome of this unique study and building our value proposition on data from Cyclacel’s ongoing studies in both hematological malignancies and solid tumors, with emphasis on our SEAMLESS Phase III pivotal trial in patients with front-line acute myeloid leukemia (AML).”
The translational Phase II study is a single institution, single arm, trial of the SCR regimen in previously treated patients with CLL or SLL. The primary objective is to evaluate the overall response rate of the regimen based on the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. Up to 40 patients will be enrolled at different dosing schedules under evaluation. Secondary endpoints include the evaluation of tolerability and toxicities, determination of duration of response, disease-free survival, and overall survival. In addition, the study will evaluate the association between response to the SCR regimen and ATM gene function in previously treated patients with CLL who have chromosomal deletion 11q22-23 by the fluorescence in-situ hybridization or FISH technique. The study will also evaluate other clinically correlated pretreatment indicators with response and time-to-event outcomes.
Patients enrolled in the study will be 18 years and older and have a diagnosis of CLL or SLL with leukemia cells containing the 11q22-23 deletion, have been previously treated with at least one prior regimen and have undergone FISH-evaluation within 3 months without intervening treatment. The latest previous dose of chemotherapy must have been administered at least 30 days prior to receiving treatment on this study.
Sapacitabine (CYC682), an orally available nucleoside analogue, is currently being evaluated in a registration-directed, Phase III trial in front-line elderly AML and Phase II trials in patients with hematological malignancies and solid tumors. Sapacitabine acts through a dual mechanism, interfering with DNA synthesis by causing single-strand DNA breaks and inducing arrest of cell cycle progression mainly at G2-Phase. Both sapacitabine and CNDAC, its major metabolite, have demonstrated potent anti-tumor activity in preclinical studies.
Over 300 patients have received sapacitabine in Phase II studies in AML, MDS, cutaneous T cell lymphoma (CTCL), and NSCLC. Sapacitabine has been administered to approximately 170 patients in five Phase I studies with both hematological malignancies and solid tumors. In December 2009, Cyclacel reported data from a randomized Phase II study including promising 1-year survival in elderly patients with AML aged 70 years or older. Sapacitabine is part of Cyclacel’s pipeline of small molecule drugs designed to target and stop uncontrolled cell division.
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