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GenSpera’s Targeted “Death Carrot” Toxin in Trials for Two Cancers

XCONOMY

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http://www.xconomy.com/texas/

GenSpera’s Targeted “Death Carrot” Toxin in Trials for Two Cancers

http://www.xconomy.com/texas/2014/03/27/gensperas-targeted-death-carrot-toxin-in-trials-for-two-cancers/

Bernadette Tansey 3/27/14

 

Craig Dionne has a record of experience in drug development and a lot of friends in the pharmaceutical industry. But when his friends first heard about the experimental drug he started working on some years ago, he says their initial reaction was alarm—to put it mildly.

“They told me I was a fool,” Dionne says affably. Dionne is CEO of San Antonio, TX-based GenSpera, which has now started a second round of early stage clinical trials on the experimental drug he took a chance on. He’s hoping the trials are about to show his friends he was right.

Back in the early 1990s, Dionne and his collaborators at Johns Hopkins University saw potential for a cancer drug in a highly potent toxin, thapsigargin, found in a common Mediterranean weed called Thapsia Garganica. You’ll find it described as the “death carrot’’ in online accounts.

Thapsigargin kills fast-growing cells. So far, so good; that’s a routine property of chemotherapy drugs. But the relative safety of classical chemotherapy agents rests on the fact that they’re more destructive to rapidly multiplying tumor cells than they are to slow-growing normal cells.

Thapsigargin doesn’t work that way—which initially made it alarming to Dionne’s friends. It’s an equal opportunity cell-killer.

“It can kill cells that grow slowly,” Dionne says. That makes it a threat to normal cells, unless a drug company can successfully tweak it. And Dionne saw a reason to try.

Like most normal cells, some cancer cells also grow slowly, such as those in tumors of the prostate. And such cancer cells can resist chemotherapy drugs that target fast-growing cells. Dionne and his collaborators at Johns Hopkins reasoned that thapsigargin might be an effective weapon against slow-growing tumor cells, if it could be modified to spare normal cells. The end result of their chemical tinkering is GenSpera’s experimental drug G-202, which has now moved into a second round of early stage clinical trials.

The compound was designed to allow the powerful toxin to move through the bloodstream in an inactive form until it’s released by an enzyme, PSMA, found at higher levels on the surface of certain tumor cells, Dionne says. He compares G-202 to a grenade with a pin ready to be pulled.

A molecule of G-202 contains a modified form of thapsigargin called 12ADT, which is linked to a small peptide. The effect of that peptide—a small chain of five amino acids—is to keep 12ADT soluble in the watery environment of the blood. More importantly, he peptide keeps the toxin inactive.

But when G-202 encounters a cell with the enzyme PSMA (prostate-specific membrane antigen) on its surface, the enzyme clips the peptide off the toxic 12ADT molecule. The toxin, now insoluble in water but highly soluble in fats, can sink through the lipid-rich outer membrane of a nearby cancer cell and start its deadly work.

Dionne says G-202 is similar to the new class of targeted cancer drugs called antibody-drug conjugates, which are also designed to deliver a toxin only to particular tumor cells. These drugs combine a toxin with an antibody engineered to bind to a specific molecule on the surface of a cancer cell. However, antibodies are large proteins whose unique amino acid sequences and folding patterns can help them fit selectively only with certain cell surface receptors.

Serotonin-producing cells develop early on in the ENS, and if this buy generic levitra development is affected, the second brain cannot form properly. You will be helped to prolong your erection in a more healthy levitra online devensec.com and natural way by this medicine. Sexual dysfunction is a common concern shared by many women. generic levitra cheap This levitra 20mg canada medicine may lead to allergic reaction in some individuals. By contrast, G-202‘s targeting agent, the small peptide, could theoretically be clipped away from its toxic payload by enzymes other than PSMA, Dionne says. If that happened, the toxin could be released in the vicinity of normal cells rather than tumor cells. This is one of the reasons why GenSpera has spent years on preclinical testing and animal studies before launching its first clinical trial of G-202 in humans in 2011, he says.

Dionne says the company also took a close look at the cardiovascular effects of the experimental drug because of its molecular mechanism of action. Thapsigargin works by disrupting a molecular pump that regulates the level of calcium ions inside cells—and ion exchanges are central to the functioning of the cardiovascular system, Dionne says. Once inside any cell, whether a tumor cell or a normal one, thapsigargin causes a damaging influx of calcium, which starts a process of programmed cell death called apoptosis.

GenSpera also had to watch out for off-target effects of G-202 for another reason. Although the target enzyme PSMA appears in a higher concentration on cells of the prostate than on many other cells, it has been found as well in certain normal tissues, such as sections of the brain, small intestine, and kidney. Dionne says G-202 can’t pass through the blood-brain barrier. Studies of the drug’s action in animals and in humans so far have not turned up significant damage to the other normal cells bearing the PSMA enzyme, he added.

However, the discovery of enriched PSMA levels in yet another type of tissue has expanded the possible uses of G-202. The enzyme is more abundant on the cells of blood vessels that bring nutrients and oxygen to solid tumors than it is in normal blood vessels. Based on this finding, GenSpera began widening its views beyond prostate cancer, Dionne says. If the toxin in G-202 could be released by PSMA in tumor blood vessels, these vessels might disintegrate, and the tumor might starve and die.

“The potential applications are so much broader,” Dionne says.

In GenSpera’s first small trials in 2011 and 2012, 44 participants with a range of different cancer types received doses of G-202. Dionne says the drug appeared to have no serious effects on the liver, cardiovascular system, or bone marrow. Kidney damage could be prevented by limiting the G-202 dose and giving trial participants plenty of water, he says.

Although the main goal of the first trial was to assess the safety of G-202, GenSpera noted that a few trial participants with advanced liver cancer survived longer than expected. Encouraged by those signs, GenSpera is now conducting a Phase II trial in up to 17 adults with advanced hepatocellular carcinoma who are no longer helped by sorafenib (Nexavar), a cancer drug co-owned by Bayer and Amgen.

In March, GenSpera also began a Phase II trial in up to 34 participants with the brain cancer glioblastoma multiforme at the University of California San Diego’s Moores Cancer Center. The company may also conduct trials in prostate and kidney cancer if it can raise the funding.

GenSpera (OTC: GNSZ) is a tiny virtual company, that had $3.6 million in cash at the end of 2013—enough to fund its operations through at least nine months of this year. The company last week announced a share offering to raise as much as $7.5 million.

Dionne, a former executive at Cephalon, which was acquired by Teva Pharmaceutical Industries (NASDAQ: TEVA) in 2011, co-founded GenSpera in 2003. The firm began its preclinical studies in 2007, when it raised its first funds from outside investors. Dionne, who is GenSpera’s chief financial officer as well as CEO, is one of the company’s staff of two full-time employees. GenSpera contracts out all its other work.

“We’re virtual out of choice,” he says.

GenSpera’s scientific advisory board includes company co-founders John Isaacs and Samuel Denmeade, who are oncology professors at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center.

GenSpera has raised $24.3 million since its inception, and the majority has come from high net worth individuals who often continue to reinvest, Dionne says. The company went public in 2009 and trades in the OTCQB tier of the Over-The-Counter Markets Group. GenSpera’s market capitalization is about $37 million.

Dionne says the company’s ideal plan is to seek a pharmaceutical company partner or buyer after conducting Phase II trials that show the potential of G-202 in solid tumors.

“We want to be valued across a range of tumor types,” Dionne says. The company has been built with the goal of making it attractive to big drug companies, he says.

“Our customer is large pharma,” Dionne says. “That’s who is ultimately going to pay us what we’re worth.”

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G-202 Represents Novel Approach for Attacking Advanced HCC

G-202 Represents Novel Approach for Attacking Advanced HCC

http://www.onclive.com/publications/oncology-live/2014/march-2014/g-202-represents-novel-approach-for-attacking-advanced-hcc/2

Devalingam Mahalingam, MD, PhD

Published Online: Monday, March 24, 2014

Prodrug chemotherapy is an exciting approach by which higher concentrations of cytotoxic or biologically active agents can be achieved at a tumor site while avoiding the systemic toxicity of a non-cell-specific toxin. One promising example of this strategy is the development of the cytotoxic agent thapsigargin, which is derived from the Thapsia garganica plant once known in Mediterranean cultures as the “death carrot.” Efforts to engineer this agent into an effective therapy for hepatocellular carcinoma (HCC) are advancing.

Thapsigargin can kill a broad spectrum of cancer cells but with detrimental effects on normal endothelial cells, fibroblasts, and osteoblasts. The molecular mechanism of action is attributed to the induction of apoptosis (cell death) by a pronounced increase in cytosolic calcium due to blockade of sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump to which thapsigargin binds with high affinity.

Due to the highly toxic characteristics of thapsigargin, the challenge was how to deliver the agent to tumors while causing the least impact on normal cells and tissue. The answer was to develop a relatively nontoxic form of thapsigargin; that is, the prodrug, which can be converted into the active cytotoxic agent at a particular location, specifically at the tumor site, for effective anticancer treatment.

In this pursuit, G-202 was generated by coupling a prostate-specific membrane antigen (PSMA)-specific peptide to an analogue of the potent thapsigargin. The daunting task was to identify a tumor-specific protein from which an appropriate peptide could be linked to the drug and make the drug inactive until the peptide could be cleaved from the drug only at the tumor site by that specific protein, such as PSMA, a glutamate carboxypeptidase type II enzyme that cleaves the acidic amino acids glutamate and aspartate. PSMA was of interest because of its unique presence in prostate cancer and most tumor endothelial cells, but not in normal vasculature or normal tissue epithelium. Of note, PSMA is also found in the vasculature of 90% of HCC tumors.

This is the best option as find this pharmacy shop now buy generic levitra you like and get enjoyed. With that formula, the science has cialis line order invented a new kind of medicine that is called generic medicine. There are many women who think whether they will ever regain their penile strength back or price viagra not. It is seriously advised by most doctors to seek for ay help purchase viagra online you could try here when you meet this certain sexual problems. The immense promise of G-202 as a future practice- changing therapy is apparent because this compound has biologic activity only after proteolytic cleavage by PSMA occurs at the tumor site. Normal healthy cells are no more susceptible to unwanted cytotoxic activity because thapsigargin is blocked by the masking peptide, which is selectively cleaved by PSMA in PSMA-positive human tumors such as prostate and HCC tumors. Within the neovasculature, the nontoxic prodrug G-202 is converted by hydrolysis into the active cytotoxic analogue of thapsigargin, 12ADT-Asp, which has the ability to trigger apoptosis by a mechanism similar to that of thapsigargin. Compared with thapsigargin alone, G-202 can achieve higher concentrations of the active agent at the tumor site while avoiding systemic toxicity.

When tested against a panel of human cancer xenografts in vivo, G-202 produced substantial tumor regression at doses that were minimally toxic to the host. These encouraging results led to a phase I open-label, single-arm, dose-escalation study in patients with advanced cancer. The study was designed to evaluate the safety and pharmacokinetics of G-202 as well as to identify a phase II dosing regimen. GenSpera, Inc, based in San Antonio, is sponsoring the research.

In all, 44 patients were recruited for the study at three US institutions, including the Cancer Therapy & Research Center at UT Health Science Center in San Antonio, which was the lead patient enrollment site. Of the participants, 28 were included in the dose-escalation portion of the study and 16 were part of an expanded cohort. Results were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.1

 

Most of the toxicities reported were mild and of grade 1 severity, with some patients experiencing increased creatinine/acute kidney injury/acute renal failure, nausea, and infusion-related reaction, ameliorated by prophylactic IV hydration, IV antiemetics, and steroid administration on the day of infusion. Five patients with HCC were enrolled in the expansion cohort. This group averaged 6 cycles of treatment per patient (range, 2-12 cycles), for a total of 29 cycles among all patients. An encouraging outcome was the observation of stable disease for more than 9 cycles in each of 2 patients.

This has led to the opening of a multicenter phase II study evaluating G-202 as second-line therapy for patients with HCC after treatment failure with sorafenib (Nexavar).2 If the early clinical finding holds true in controlling progression of HCC with minimal toxicity to patients, and a successful clinical development program is completed, G-202 could one day become a treatment option for patients with advanced HCC.

New therapies are urgently needed for this patient population. HCC ranks third in cancer deaths worldwide, with ~360,000 deaths annually. The majority (75%) of the world’s patients with HCC are in Asia-Pacific Rim countries. In the United States, the incidence of HCC is increasing and has risen at a faster rate in the Latino/Hispanic population than among non-Hispanic whites. Currently, the only FDA-approved drug for HCC is sorafenib, which gained an indication for unresectable HCC in 2007 after clinical trial findings demonstrated a 3-month improvement in overall survival versus placebo.
– See more at: http://www.onclive.com/publications/oncology-live/2014/march-2014/g-202-represents-novel-approach-for-attacking-advanced-hcc/2#sthash.TX7mxRWe.dpuf

 

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GenSpera registers for public offering

 

 

Mar 21, 2014, 1:15pm CDT

GenSpera registers for public offering

http://www.bizjournals.com/sanantonio/blog/2014/03/genspera-registers-for-public-offering.html

Biotech firm GenSpera has filed with the SEC for a future public offering.

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W. Scott Bailey

GenSpera Inc. has filed a registration with the U.S. Securities and Exchange Commission for a public offering.

The filing does not specify how many shares of stock the San Antonio-based biotech company plans to offer or at what price.

It does indicate that GenSpera (GNSZ: OTC) intends to use the proceeds from the sale of stock to fund Phase II clinical trials of its lead drug G-202 in patients with liver and brain cancer. The company also plans to dedicate a portion of those proceeds for working capital.

GenSpera, which is still in the research-and-development phase for its lead drug, reported a net loss of $2 million in the fourth quarter of 2013.

On Tuesday, I reported that GenSpera has launched a Phase II clinical trial for G-202 with patients who have glioblastoma multiforme, the most prevalent type of primary brain cancer. The trial will be conducted at the University of California at San Diego’s Moores Cancer Center.

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GenSpera enrolls brain cancer mid-stage trial with ‘grenade’ delivery

GenSpera enrolls brain cancer mid-stage trial with ‘grenade’ delivery

Blood-brain barrier in glioblastoma? ‘We don’t need to worry about it.’

http://www.fiercedrugdelivery.com/search/site/genspera

The weed Thapsia garganica, which provides the active ingredient thapsigargin for G-202–Courtesy of GenSpera

March 19, 2014 | By Michael Gibney

Texas cancer drug delivery specialist GenSpera is enrolling a new study for its molecular “grenade” candidate G-202. This time it’s a Phase II for the treatment of the notoriously aggressive brain cancer glioblastoma.

The G-202 candidate in question is the same as one that garnered GenSpera positive results in a Phase I study ending in October last year. That trial aimed at solid tumors with a subset of patients with hepatocellular carcinoma, a type of liver cancer.

Along with a research team at the University of California in San Diego, GenSpera will conduct the new study in two stages in up to 34 patients with recurrent forms of glioblastoma who have already undergone at least one major treatment–surgery or radiation. The drug is designed to be delivered via intravenous infusion for about an hour over the course of three days.

As an endpoint, GenSpera is looking for patients to be progression-free at 6 months. Historically, GenSpera CEO Craig Dionne told FierceDrugDelivery, about 15% of glioblastoma patients are progression-free by this point, and GenSpera is aiming to boost that number to 30%.
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G-202 has shown to be effective before. But there are many delivery challenges that come with getting drugs past the blood-brain barrier, and here’s where GenSpera’s drug could have an edge: it doesn’t need to cross the barrier and its drugs work from within the blood vessels in the tumor.

Since G-202 is designed to act on the blood vessels inside a tumor, constricting them so as to starve the tumor, Dionne said, it doesn’t come up against the same challenges as other drugs that need to cross the endothelial cells to get into the tumor’s mainframe.

“Our approach to the blood-brain barrier,” Dionne said, “is we don’t need to worry about it.”

Dionne compares G-202’s release mechanism to a “grenade” complete with a “pin” that’s pulled at a specific site in a tumor’s blood vessel. G-202 is the first to take advantage of the enzymatic action of the prostate-specific membrane antigen, PSMA, that exists in abundance at tumors such as glioblastoma. The PSMA enzyme pulls off a peptide cap on the drug that delivers a hefty dose of the specifically deadly toxin 12ADT.

“If you look at glioblastoma, it is highly vascularized and makes a lot of PSMA, which is perfect for us,” Dionne said. “The toxin is targeted with the antibody drug conjugate and, taking advantage of the enzymatic action, it delivers thousands of active molecules. The amplification is a huge part.”

The toxin 12ADT is the final component of the uniquely designed drug. Its active ingredient, thapsigargin, is derived from a Mediterranean wild weed called Thapsia garganica, Dionne said, which works by disrupting a pump that regulates calcium levels in the blood vessel cells. The toxin is extremely potent, more so even than common cancer drugs such as doxorubicin, and kills independently of cell division rate, which means it can affect slow-growing tumors or even cancer stem cells that can linger after a tumor is mostly eradicated. According to Dionne, once the toxin is released, it is highly lipophilic and stays there in the tumor.

GenSpera’s other Phase II trial for G-202 in hepatocellular carcinoma is also currently being enrolled, Dionne said, with 16 patients on board.

– here’s the release

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AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference: October 2013

  • AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference: October 2013
    the company started a Phase II study in patients with recurrent high-grade glioma 10/22/13 Genspera Inc. (San Antonio) G-202 A thapsigargin-based prostate-specific membrane antigen-activated prodrug Hepatocellular carcinoma Data showed that 27% of patients exhibited stable disease 10/23/13 Immunogen Inc. (Waltham, Mass.) SAR566658 An antibody-drug conjugate targeted to CA6 Ovarian, breast and other epithelial cancers Interim Phase I data showed it is generally well tolerated and can induce

    BioWorld Insight | Monday, November 11, 2013

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Genspera

BioWorld Today | Wednesday, October 23, 2013

http://www.bioworld.com/bioworld_search/GenSpera
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Genspera Inc., of San Antonio, reported Phase I data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston showing that 27 percent of patients receiving G-202, a thapsigargin-based prostate-specific membrane antigen-activated prodrug, exhibited stable disease

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Molecular ‘grenades’ from GenSpera reel in PhI liver cancer success

Molecular ‘grenades’ from GenSpera reel in PhI liver cancer success

http://www.fiercedrugdelivery.com/story/molecular-grenades-genspera-reel-phi-liver-cancer-success/2013-10-22

October 22, 2013 | By Michael Gibney

Texas biotech GenSpera touted successful Phase I data this week for its prodrug candidate designed to target solid tumors. The drug is the first to take advantage of the enzymatic action of the prostate-specific membrane antigen (PSMA), which effectively “pulls the pin on the grenade” of the uniquely delivered drug.

In its first-in-human study of GenSpera’s lead candidate G-202 in 44 patients with solid tumors who failed on earlier therapies, 27% had a prolonged stable disease of more than 9 months. In a subset with hepatocellular carcinoma, a type of liver cancer, two out of 5 patients showed stabilization after failing on previous standards of care.

The prodrug includes the cell-killing agent 12ADT, which is injected attached to a targeting and masking peptide. GenSpera CEO Craig Dionne likens this to a grenade with a pin. When the peptide reaches the tumor cell, it encounters the PSMA enzyme, which plays a double role: first, it acts as a targeting mechanism for the peptide to reach the tumor, and second, it cleaves the peptide to release the cell-killing 12ADT within the cell, like a pin from the grenade.
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“The beauty of the molecule is it should be activated only in the tumor,” Dionne told FierceDrugDelivery. “It’s designed not to come back into the bloodstream–in animal studies, there was no effect on the liver, no effect on the cardiovascular system, no effect on bone marrow. We do see some damage in the kidney on high doses, which is expected and completely reversible, but overall it shows a tremendous application from animals to humans.”

GenSpera is now enrolling a Phase II trial to further explore G-202’s effect on liver cancer compared with the treatment Nexavar, marketed by Bayer and Onyx Pharmaceuticals ($ONXX). GenSpera expects preliminary results early next year with 9 patients enrolled already, Dionne said. All included, the publicly traded company has raised about $25 million, which Dionne said should take them through this study and toward uplisting to the Nasdaq.

The company also plans to begin testing the compound on glioblastoma brain tumors early next year.

“Because we take advantage of the enzymatic activity of PSMA, it’s a huge amplification,” Dionne said. “For every active enzyme on the surface of the cell, we have 1000 active warheads. And we’re the only ones taking advantage of the enzymatic action of PSMA.”

– here’s the release

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Advances in regenerative medicine may let patients grow own transplants

Modern medicine:

Advances in regenerative medicine may let patients grow own transplants

http://www.msnbc.msn.com/id/48976348/ns/health-mens_health/

By Maggie Fox

NBC News

A few years ago, Dr. Anthony Atala’s lab at Wake Forest University got good at making ears. They were growing new ears on a scaffold using patient’s cells, because so many soldiers were losing their ears in explosions. Now the Department of Defense has a project that’s closer to Atala’s heart: making new genitals for soldiers who have stepped on bombs.

Other labs are still moving forward with the ear project for the military.  But Atala has special expertise dating back to his days as a pediatric urologist. He’s already grown bladders using a patient’s own cells, and he’s made penises that rabbits were able to put to their proper use, fathering litters of new little bunnies. He hopes to use this expertise to help rebuild the bodies of veterans wounded in Iraq and Afghanistan, as well as men and boys injured in car accidents.

Atala is one of the pioneers of regenerative medicine. But the field has
taken off in a big way, attracting biotechnology companies, the U.S.
military and academic labs, which are working to literally make the blind see and the lame walk again. They’re perfecting spray-on skin and to mass-produce new body parts using bioprinters based on the jet printers attached to your home computer.

“Right now, the way these organs are made is creating them one by one. By bringing the bioprinting in, we can scale it up,” says Atala, whose lab has contracts with the four-year-old Armed Forces Institute of Regenerative Medicine (AFIRM), biotechnology companies and private foundations.

All of this technology is years away from the doctor’s office. The most
advanced treatments have just begun the very earliest stages of human testing. But all evidence points to the tantalizing prospect of
grow-your-own organs and possibly even limbs within a decade or so, and some approaches, such as muscle transplants and spray-on skin, are helping a lucky few now.

Atala’s lab in 2006 made the first full organ ever grown and implanted into a human – the bladder – and the rabbit penises were the first solid organs. A new bid from AFIRM caught his eye. It called for experts in rebuilding the lower abdomen, the genitals, the pelvic area and the bladder.

These injuries are among the least talked-about but among the most horrible affecting war veterans. The improvised explosive devices, or IEDs, planted by insurgents across Iraq and Afghanistan blow off feet, legs and arms, and they can especially damage the pelvic areas that are difficult to protect with body armor.

Atala’s lab is also working to make kidneys, muscle implants, and even to find ways to get fingers to regenerate on their own. (It has to do with waking up some very powerful DNA that goes to sleep soon after a fetus develops). AFIRM’s mission is to align labs like Atala’s with others around the country, getting them to collaborate on projects rather than compete.  AFIRM currently funds around 50 research labs, including leaders such as the University of Pittsburgh Medical Center, Rutgers University, the Cleveland Clinic and Rice University.

“We don’t really feel that other groups are competition at all,” Atala says “Our interest is really to get these technologies into patients. We consider the disease the competition.”

Spray-on skin One area of intense competition – or collaboration – is in spraying on new skin. AFIRM is funding several projects testing a product that uses a patient’s own skin cells, so that rejection is not an issue. Old-fashioned skin grafts may close a wound or a burn, but they don’t heal prettily.  ReCell is a product, more of a process really, that uses a small plug of a patient’s own skin, broken down into a soup using enzymes. Cells known as keratinocytes, which give skin its structure, and the melanocytes, which give color, are pulled out, mixed into a liquid suspension and then sprayed over the damaged area.

It’s a thin layer but the cells quickly multiply and, if the process is done right, form an even layer of new skin within days. The result is much more natural-looking than a graft.

Skin is easier to heal because it’s a relatively simple organ and on the
surface of the body. Limbs are more complicated – they are made up of bone, muscle, nerves, connective tissue and also skin.

Labs are taking a more traditional approach in trying to restore limbs, by transplanting them. But even there regenerative medicine can play a role.  This is where stem cell research comes in. Stem cells are the body’s master cells, and there are several kinds. People have stem cells known as adult stem cells all through their bodies, and they are already partly “educated” to become blood, muscle, bone or nerve cells.

These cells divide and multiply to produce muscle, bones and blood, and they also secrete compounds that help existing tissue and cells regenerate. Some of the projects on AFIRM’s wish list include calls for labs that can combine techniques used to build new body parts with the use of stem cells to help them generate and integrate with the rest of the body.

More powerful cells come from embryos that have barely begun to develop. An entire human body, the collection of muscle, bone, brain, blood, nerves and organs, all develops from the ball of just a few cells that forms days after fertilization. Each one of these cells, known as human embryonic stem cells, contains all the coding needed to make every cell type in the body.
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Helping the blind see In January, scientists at Advanced Cell Technology, a company based in Massachusetts, reported they had used some of these human embryonic stem cells to partially restore vision in two legally blind patients. First they “trained” the cells by incubating them in a nourishing soup of chemicals designed to make them differentiate into retinal cells. The stem cells, infused directly into the eye, regenerated cells known as retinal pigment epithelium cells.

One patient said she can thread needles again and another has been able to resume shopping on her own. ACT has since gotten permission to treat more patients with higher doses of the cells, now that they have at least been shown not to cause any harm. They’re going after patients with degenerative eye diseases such as age-related macular degeneration and Stargardt disease.  In both conditions the cells in the retina gradually die and patients go slowly and irreversibly blind.

They’ve treated 11 more patients, says ACT’s chief medical officer Dr.
Robert Lanza. “In all the patients we have been seeing a very real
biological signal,” Lanza told NBC News. “We have been very pleased because we are talking about very advanced stage patients, and there’s really no treatment for them.”

The experiments, known as clinical trials, are strictly regulated. In the
early stages of human testing, where ACT is now with stem cells, Stage 1 trials recruit only volunteers with advanced, severe disease who have little to lose. The tests are not aimed at showing whether the treatment works, but to ensure that it doesn’t do any harm. Showing efficacy is a big bonus.

“We are far enough along now that we can go into patients with better
vision. That is where we think we will see a very dramatic improvement,” said Lanza.

It doesn’t always go this well. ACT was neck and neck with another company called Geron to be the first to test human embryonic stem cells in people. Geron got there first in 2010, infusing the cells into a young man injured in a car accident, as well as three others. The hope was to regenerate their severed spinal cords. Again, these first patients were treated experimentally only to show the approach was safe and no one dared hope they’d actually improve. And none of them did. Geron dropped its stem cell program in November 2011, saying it wanted to focus on cancer drugs instead.

Lanza said the eyes are a great place to test new treatments because
researchers can literally look in there and see what’s happening. The
spine’s a little harder, but other labs are trying to help there, too.

‘I was afraid it would be a dream’ Ted Harada had a second infusion of stem cells last month. The 40-year-old former Fedex employee has Lou Gehrig’s disease, medically known as amyotrophic lateral sclerosis or ALS. It attacks nerves called motor neurons, gradually and inexorably paralyzing its victims. It’s always fatal as patients lose every bit of their ability to move, even to breathe. There’s no treatment and no cure.

Harada is hopeful enough to have tried the highly experimental treatment not once but twice. It’s painful – surgeons have to cut open his spine and infuse the stem cells right into his spinal fluid. But the last time Harada was treated, he went from walking with a cane to running with his kids – a transformation that made him an instant television celebrity.

“The results I saw were nothing short of miraculous,” says Harada, who lives in Georgia and who got treated at Emory University. “Within two weeks I started feeling my legs getting better. I was afraid it would be a dream and I would wake up and it would be gone again.”

And the effects did gradually wear off, Harada says. “All of a sudden I
started noticing fatigue in my legs,” he told NBC News. “I started noticing trembling, shaking in my legs. If you do a lot of weight lifting you know that rubbery feeling your legs get when they are spent?” That’s how he felt.

In August, Harada got a second infusion of stem cells, which are made by a company called Neuralstem, this time in his neck. “There were a lot of reasons to think this could not safely be done. The spinal cord itself is very precious real estate,” says Dr. Eva Feldman, a neurologist at the University of Michigan who is working on the ALS trial. “You are putting a needle into the spinal cord.”

Feldman admits that researchers on the trial don’t fully understand what the cells are doing. In animals, she says, they form new connections with damaged motor neuron cells in the spine. “They essentially nurture the sick cells into health,” she said. They secrete compounds known as growth factors that nourish the cells in the spinal cord. “They go in there and clean it up so that the whole environment looks less inflammatory … We are not letting the fact that we don’t fully understand how they work prevent us from using
them.”

Harada thinks he may already be feeling something but admits it might be wishful thinking. Trained nurses will measure his muscle strength to see if the new treatment has helped. “I am determined and relentless for them to utilize me as their guinea pig to figure out what is helping me and they can translate this into helping all the other cases of ALS,” says Harada. “I don’t want to provide false hope.”

That’s one thing that worries Dr. Paul Knoepfler, a professor of medicine at the University of California Davis. “There are a lot of clinics sprouting up, offering people stem cell treatment for anything that might be ailing you,” Knoepfler said in a telephone interview. “Some of these pop up in a strip mall, even. They might charge $20,000.”

Yet few, if any, have any real medical credibility, says Knoepfler. “For the most part, the science just isn’t there and yet people are talking about spending a whole chunk of their life savings and the clinic could be totally bogus,” he said.

“We are worried not only for specific patients, but it may tarnish the whole field generally if we have patients getting hurt or even killed by so-called stem cell treatments.”

(c) 2012 NBCNews.com Reprints

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R&D Changes Foreseen After Supreme Court Obamacare Decision

R&D Changes Foreseen After Supreme Court Obamacare Decision

http://www.genengnews.com/keywordsandtools/print/3/27740/

Insight & Intelligence™ : Jul 5, 2012

Innovative drugs that offer clear superiority over existing products likely among beneficiaries of overhaul.

Alex Philippidis

By upholding President Barack Obama’s healthcare overhaul, the U.S. Supreme Court set the stage for several key changes to drug development, industry executives and observers agreed in interviews.

Craig A. Dionne, Ph.D., president and CEO of GenSpera, told GEN that biopharma startups won’t win the funding they need without showing investors solid results earlier in development. Those companies, he said, must offer investors clear evidence that their new drugs offer “clearly superior” efficacy than existing products, or else risk reduced reimbursement from government and private insurance programs under the Patient Protection and Affordable Care Act.

“We have to develop drugs that are very highly and clear differentiated in such a way that they can command premium pricing, and command reimbursement,” Dr. Dionne said. “In oncology, which is our world, that could be something as simple as no effect on the bone marrow, so you no longer need all those supportive cares and all those other expenses that come with a drug with that kind of side effect profile.”

“Companies won’t even get started unless they can start making that argument. And they’re not going to get continued funding unless they can make that argument for premium pricing in the future,” Dr. Dionne added.

Richard Garr, CEO of Neuralstem, told GEN the law will aid drug R&D through its extension of insurance to 32 million more people, and its prohibition on insurers rejecting patients for pre-existing conditions. The latter, he said, should help kickstart research and product development of genetic diagnostics, and for rare disease therapy developers like his company.
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“You can’t overstate the importance of this act with respect to the impact it will have on people saying, ‘If we think we have something that’s worth pursuing here on the science side, now we have a much higher comfort level on the business side also,” Garr said. “I would think you will see a flood of genomic companies and testing. I think people will be much more responsive than they ever had been to that, now that they don’t have to worry about their insurance being canceled because they know.”

The healthcare law incorporated the Biologics Price Competition and Innovation (BPCI) Act of 2009, which mandates creation of an abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product.

Among companies interested in BPCI are Quintessence Biosciences, a developer of anti-cancer, protein-based therapeutics.

Laura E. Strong, Ph.D., Quintessence’s president and COO, told GEN BPCI’s 12-year data exclusivity period is especially welcome by her company, which envisions itself a reference drug developer for future biosimilars.

“One of the issues that’s really important when you think about investment in innovation in biotech and pharma is, What’s the return on investment going to be? Having a more certain marketplace is definitely an improvement,” Dr. Strong said.

Action on biosimilars, however, will have to await FDA approval of final guidances for implementing BPCI; the agency issued three draft guidances on February 9.

FDA isn’t the only Washington hurdle for biosimilars. Obama’s administration wants to shrink exclusivity to seven years, claiming it would save $4 billion over 10 years; Congressional committees have sided with industry. “Our expectation is that the administration would continue those efforts, and we believe that would be certainly problematic,” Todd Gillenwater, svp, public policy with the California Healthcare Institute, told GEN.

He said industry will also continue fighting the law’s Independent Payment Advisory Board focused on cutting Medicaid costs. Biopharma groups say quality of care would be sacrificed, adding the board of 15 unelected presidential appointees requires more oversight.

Industry is also waiting for the states to establish the law’s insurance exchanges. “States continue to feel a lot of budgetary pressure, and there are other factors that may contribute to them not being able to move forward as quickly as they’d like with implementation,” Christie Bloomquist, a partner in the Washington, D.C., office of Hogan Lovells, told GEN. One such factor surfaced in recent days, as officials in Iowa, Louisiana, Mississippi, South Carolina, Texas, and Wisconsin said they may join Florida, where Gov. Rick Scott said Sunday he would not permit Medicaid expansion. All seven states are led by Republicans.

While biopharmas chafe at some provisions, industry mostly favors the healthcare overhaul. But to see the biggest benefit, companies will have to balance their desire to grow their pipelines and advance drugs with the law’s likely reality that investors will limit already-scarce dollars to treatments showing the best results.

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Another Twist on ADCs

Another Twist on ADCs

Researchers at Johns Hopkins University have developed a new twist on antibody-drug-conjugates (ADCs): a drug related to the plant poison thapsigargin, coupled to a peptide that binds to prostate-specific membrane antigen (PSMA), which is not really prostate-specific, but instead is expressed on endothelial cells in the microenvironment of many solid tumors. Thapsigargin is a poison that inhibits SERCA, a calcium pump which is critical for cells to maintain their membrane potential. Untargeted, the drug is far too toxic to use medically. But you can slow levitra price down this change by leading a stress free life and taking an anti-impotency drug. Drink plentiful water discount buy viagra and reduced the amount of sodium you take all through the day. Normal atmospheric pressure (14.7psi at sea level) outside the cylinder and near the pubic bone area will force blood to rush in to satisfy the differences between that pressure and the one inside the cylinder. buy cialis no prescription Thus by using this medication every man will be able to knock off impotence from their life. online cialis But the authors showed that by combining it with the PSMA targeting peptide, they were able to make a prodrug, G202, which achieved “substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host.” These results appeared in the June 28, 2012, issue of Science Translational Medicine. G202 is being developed by GenSpera Inc. The drug is currently in Phase I trials.

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