Acceleron’s ACE-041 Combined with a VEGF Inhibitor Shows Potent Activity in Preclinical Model of VEGF-Resistant Renal Cell Carcinoma

— Enhanced Anti-Tumor Activity Achieved via Combination of Two Distinct Anti-Angiogenic Drugs presented at the AACR Annual Meeting 2012 —

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Apr 3, 2012 – Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, announced that collaborators at Beth Israel Deaconess Medical Center presented preclinical data today at the American Association for Cancer Research (AACR) Annual Meeting 2012 which showed that ACE-041, an activin-receptor like kinase 1 (ALK1) receptor ligand trap, when used in combination with sunitinib, inhibited tumor growth in a model of VEGF-inhibitor-resistant renal cell carcinoma (RCC).

Anti-angiogenesis therapies, including the VEGF-inhibitor sunitinib, are currently the standard of care in metastatic RCC. While these treatments cause tumor shrinkage and extend progression-free survival in many patients, the responses are typically short-lived due to the development of drug resistance. Mice bearing A498 and 786-0 human RCC xenografts that receive anti-VEGF treatment mirror this clinical experience with a period of tumor stabilization that is followed by the restoration of angiogenesis and resumption of growth despite continued drug administration. The preclinical data, presented by Rupal Bhatt, M.D., Ph.D., Assistant Professor, Hematology-Oncology, Beth Israel Deaconess Medical Center provide evidence that combining two distinct anti-angiogenic drugs, a VEGF inhibitor and ACE-041, may produce an enhanced therapeutic effect in the treatment of metastatic RCC.

Preclinical Study Description and Results

Two renal cell carcinoma cell lines (A498 and 786-O) were used in a mouse xenograft model. In each tumor cell line, mice treated with the combination of ACE-041 and sunitinib slowed tumor growth to a greater extent than either agent alone. Additionally, the combination of ACE-041 and sunitinib prevented the restoration of tumor perfusion during the resistant phase of sunitinib-alone treatment and lowers tumor perfusion to a greater extent than sunitinib-alone.

“These data demonstrate that blocking ALK1 ligand signaling, either alone or in combination with other anti-angiogenesis therapies, may be an attractive strategy for treatment of renal cell carcinoma,” said Dr. Bhatt.

“There is increasing evidence that combining anti-angiogenesis inhibitors with distinct mechanisms of action, such as a VEGF inhibitor with an ALK1 ligand trap, like ACE-041, can more effectively inhibit tumor angiogenesis,” said Matthew Sherman, M.D., Chief Medical Officer at Acceleron. “We believe this approach holds great promise and we’re excited to pursue Phase 2 studies of ACE-041 in combination with VEGF inhibitors later this year.”

About ACE-041

ACE-041 is an ALK1 ligand trap that inhibits angiogenesis by preventing BMP9 and BMP10, members of the TGFβ protein superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a receptor found on proliferating endothelial cells. ACE-041 inhibits ALK1 signaling, which is required for the development of mature, functional capillary networks. In animal studies, treatment with ACE-041 inhibits tumor angiogenesis and growth. In a clinical study of patients with advanced, refractory solid tumors, treatment with ACE-041 was generally well-tolerated and antitumor activity was observed, resulting in tumor shrinkage and stabilization of disease. ACE-041 is being studied in a Phase 2 clinical trial in patients with squamous cell carcinoma of the head and neck.

About Acceleron

Acceleron is a privately-held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel protein therapeutics for orphan diseases and cancer. Acceleron’s scientific approach takes advantage of its unique insight to discover first-in-class therapies based on the TGF-β protein superfamily. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company’s internal GMP manufacturing capability to advance its therapeutic programs rapidly and efficiently. The investors in Acceleron include Advanced Technology Ventures, Alkermes, Avalon Ventures, Bessemer Ventures, Celgene, Flagship Ventures, MPM BioEquities, OrbiMed Advisors, Polaris Ventures, QVT Financial, Sutter Hill Ventures and Venrock. For further information on Acceleron, please visit http://www.acceleronpharma.com.

Contact: Acceleron Pharma:
Steven Ertel, 617-649-9234
Chief Business Officer
or
Suda Communications LLC
Maureen L. Suda, 585-387-9248
Media

Posted: April 2012

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Oncoprex Shows Synergistic Tumor Suppression in Combination with AKT Inhibitor MK2206

Data Presented at the American Association for Cancer Research 2012 Annual Meeting

CHICAGO and AUSTIN, Texas, April 2, 2012 /PRNewswire/ — Genprex, Inc. — New data demonstrating the anti-cancer activities of Oncoprex® were presented at the 2012 Annual Meeting of the American Association for Cancer Research (AACR) in Chicago, IL.  The study, “Synergistic antitumor activity of AKT inhibitor MK2206 and FUS1 nanoparticles in LKB1 mutant NSCLC” (Meng J, Lara-Guerra H, Ji L, Roth JA) is authored by a team of investigators from The University of Texas MD Anderson Cancer Center.  The paper is included in the Proceedings of the Annual Meeting of the American Association for Cancer Research, 2012, Abstract 870.  The preclinical study demonstrates that when Oncoprex is combined with Merck’s MK2206[1], the combination of therapies is more effective in suppressing growth in LKB1 mutant tumors than either of the single agents in animal models bearing H322 LKB1-mutant human lung cancer tumors.  The treatment with the combination of Oncoprex and MK2206 resulted in tumor volume reduction of greater than 2.5 times the tumor reduction achieved with MK2206 alone.

A phase I clinical trial evaluating intravenous Oncoprex monotherapy, also known as FUS1 nanoparticles, demonstrated antitumor activity in lung cancer patients.  Previously published animal studies showed synergistic cancer-killing activity when Oncoprex is combined with a variety of kinase inhibitory agents including erlotinib and gefitinib.  A phase I/II clinical trial evaluating Oncoprex combined with Tarceva® (erlotinib) in lung cancer patients without the EGF receptor mutation or patients who have failed Tarceva therapy will initiate in 2012. 

David J. Tomasso, chief operating and business officer at Genprex commented, “Many patients cannot benefit from targeted cancer therapies due to the patient’s genomic characteristics. We are developing Oncoprex combination therapies to expand patient populations benefiting from targeted therapies and to unlock the unrealized potential of a variety of targeted kinase inhibitory drugs. This study broadens the potential application of Oncoprex to include combinations with AKT inhibitors such as MK2206.”

Contact:      
David Tomasso
Chief Operating and Business Officer
Genprex, Inc.
Phone: 512-597-5900
http://www.genprex.com
[1] MK2206, an investigational cancer therapy developed by Merck & Co., is a highly selective non-ATP competitive allosteric inhibitor of AKT currently being evaluated in early-phase clinical trials for treatment of cancer patients with solid tumors.

SOURCE Genprex, Inc.

Posted: April 2012

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First Bedside Gene Test Shows Promise

THURSDAY, March 29 (HealthDay News) — For the first time, a genetic test done at a patient’s bedside helped doctors choose the right medicine, Canadian researchers report.

The test, which can be done by nurses and others, was able to identify patients in whom the blood thinner Plavix might be ineffective, putting the patients at risk for heart attacks or strokes.

“One of the shortcomings we have in medicine right now is that there isn’t a quick and effective way of identifying these genetic variants,” said lead researcher Dr. Derek So, from the University of Ottawa Heart Institute.

“We have created the world’s first point-of-care genetic test,” he said. “We now have the means of selecting the right drug for the right patient.”

The report was published in the March 29 online edition of The Lancet.

To prove the test works, So’s team randomly assigned 200 patients to either receive screening for a gene called CYP2C19*2 using the gene test, or to regular care.

All of the patients had undergone a procedure called angioplasty to open a blocked heart artery and had a stent placed there to keep the vessel open.

Standard care after the procedure is to give patients Plavix to prevent clotting. However, many patients have this gene mutation, which makes the drug ineffective and patients more likely to develop a clot that could result in a heart attack or stroke.

Among those with European ancestry, about 30 percent have this mutation, and among Asians it’s as high as 50 percent, the researchers noted.

Normally, after starting a patient on Plavix, a platelet function blood test is done to see how the patient reacts to the drug.

In this study, those getting the gene test were given a low dose of Plavix and the others received a regular dose. Both groups were given the drug so the researchers could judge the accuracy of the rapid gene test using the platelet function test as confirmation.

The researchers found the gene test accurately identified all the patients with the gene mutation. Patients who had the mutation were switched to a newer drug called Effient, which is not affected by this mutation.

After one week, 30 percent of those in the standard group were identified by the platelet function test as having a raised risk for clotting, while none of those in the gene test group showed an increased risk for clotting, So said.

“This is the first step required for personalized medicine,” So said. “Ours is a proof-of-concept study. Now that we have this tool we can apply this same technology to different groups of patients and alter patient’s therapy. We have taken bench to bedside.”

One expert, Dr. Kirk Garratt, the clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City, thinks more proof is needed of the benefits of this particular test, but its real value is its potential.

“Before anybody can get too worked up about the application of this technology in the clinic, we will have to see evidence that acting on the information provided actually yields benefit,” Garratt said.

“There is one really dazzling benefit,” he added. “These researchers have now shown that you can take a minimally trained allied health person and do accurate genotyping on patients in the clinic — that is really big news.”

The test is given by taking a swab from the patient’s cheek, putting it in a machine and getting a result in about an hour. The test can be done by people who have never done genetic testing after just 30 minutes of training, So said.

Larger trials will be needed to see if the test makes a difference in patient outcomes, So noted. Spartan Biosciences, which makes the test used in the study, funded the trial.

In terms of cost, the machine goes for about $10,000 and each test kit is about $300, So said. That’s relatively inexpensive if it prevents patients from getting the wrong drug.

One advantage is that the test can be given before patients receive their first dose of Plavix, So pointed out.

In addition, as Plavix (clopidogrel) becomes a generic drug — as it is in Canada — its cost goes down, while the newer drugs like Effient (prasugrel) and Brilinta (ticagrelor) are very expensive and are associated with an increased risk of bleeding, he noted.

Commenting on the study, Dr. Amber Beitelshees, an assistant professor of medicine at the University of Maryland School of Medicine in Baltimore and author of an accompanying journal editorial, said that “for the first time, a point-of-care genetic test has been developed which can be used to rapidly screen individuals who carry a particular gene and may benefit from an anti-platelet drug other than Plavix.”

Beitelshees added that “this is important because rapid genotyping is necessary in order for genotype-guided therapy to be incorporated into clinical care of patients undergoing coronary interventions outside of clinical trials.”

However, another expert thinks much more needs to be shown about the value of this test before it can start to be widely used.

Dr. Gregg Fonarow, director of the Ahmanson-UCLA Cardiomyopathy Center and co-director of the UCLA Preventative Cardiology Program in Los Angeles, said that “there has been great interest in using genetic testing information to guide selection of medications and dosing, yet to date there has been little evidence that this testing can improve clinical outcomes.”

However, Fonarow continued, “as neither genetic testing for variant CYP2C19 or platelet-function testing has been demonstrated to improve clinical outcomes and routine use of these tests are not currently recommended, further studies demonstrating any clinical utility, if any, are needed.”

More information

For more on angioplasty, visit the U.S. National Heart, Lung, and Blood Institute.

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Divergent Shows Off Its Goodreads Choice Win

Posted by Patrick on February 28, 2012

Goodreads just got some real-world cred. This past December Veronica Roth’s dystopian novel Divergent took home top honors in the Goodreads Choice Awards for Young Adult Fantasy & Science Fiction and went on to win the biggest prize of all, Favorite Book of 2011. Its publisher, Harper Collins, decided to celebrate the win by placing a special Goodreads Choice Winner badge on the paperback edition. The paperback debuts today, and here is the cover in all its Goodreads glory:

Hopefully, it won’t be long before the Goodreads Choice badge is as common as the Oprah’s Book Club sticker once was. Congratulations again to Veronica Roth for her win and to all the readers who voted for her!

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