Replies to post #68340 on Biotech Values

[ThomasS]

VRUS/ITMN: About time! I believe it quite notable that these are treatment-naive patients, which speaks volumes.
I'll go out on a limb and suggest (hope) that this combo is quite effective.

[Preciouslife1]

Souped-up immune cells catch even disguised HIV
Sun Nov 9, 2008 4:48pm EST

http://www.reuters.com/article/rbssHealthcareNews/idUSN0940487520081109?sp=true

WASHINGTON, Nov 9 (Reuters) - Genetically engineered immune cells can spot the AIDS virus even when it tries to disguise itself, offering a potential new way to treat the incurable infection, researchers reported on Sunday.

The killer T-cells, dubbed "assassin" cells, were able to recognize other cells infected by HIV and slow the spread of the virus in lab dishes.

If the approach works in people, it might provide a new route of treating infection with the deadly human imunnodeficiency virus, the researchers in the United States and Britain said.

"Billions of these anti-HIV warriors can be generated in two weeks," said Angel Varela-Rohena of the University of Pennsylvania, who helped lead the study.

In a second, unrelated report, researchers testing Dutch biotechnology firm Crucell NV's (CRCL.AS:) (CRXL.O) experimental AIDS vaccine said it prevented infection in six monkeys.

The animals were infected with a monkey version of HIV called SIV, and the vaccine used a virus that is dangerous to use in humans, so it is not ready for human tests.

But, writing in the journal Nature, Dr. Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston and colleagues said it shows there is still hope for developing a vaccine against AIDS.

The AIDS virus, which infects 33 million people globally, is especially hard to fight. Like all viruses, it hijacks cells in its victims, forcing them to become little viral factories and make more virus.

ESCAPE AND EVADE

HIV is even more insidious, attacking immune system cells called CD4 T cells, which help mount a defense. It can also disguise itself to escape CD8 killer cells, also known as cytotoxic T lymphocytes or CTLs.

"CTLs are crucial for the control of HIV infection. Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host," the researchers wrote in their report, published in the journal Nature Medicine.

One good defense allows HIV to hide a protein called HLA-I-associated antigen.

Varela-Rohena and colleagues took T-cells from an HIV patient and created a genetically engineered version that recognizes this deception.

"It is possible to improve on nature when it comes to preventing HIV CTL escape," they wrote.

Not only could the engineered T-cells see HIV strains that had escaped detection by natural T-cells, "but the engineered T cells responded in a much more vigorous fashion so that far fewer T-cells were required to control infection," Penn's James Riley, who also worked on the study, said in a statement.

"In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again, weakening itself along the way," added Andy Sewell of Britain's Cardiff University.

Perhaps having to mutate will weaken the virus, the researchers said.
They plan to test the T-cell treatment in HIV patients next year.

"We have managed to engineer a receptor that is able to detect HIV's key fingerprints and is able to clear HIV infection in the laboratory," said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd, a British company launched in July that owns the rights to the technology. "If we can translate those results in the clinic, we could at last have a very powerful therapy on our hands."
(Reporting by Maggie Fox; Editing by Cynthia Osterman)

[DewDiligence]

Re: All-oral HCV combination study

Roche had been promising the start of an all-oral HCV trial in the near future (#msg-32650999).

(I cited such a development in a recent thread questioning the underlying rationale of ZGEN’s IFN-lambda program (#msg-32638280).)

Until recently, the only question was whether Roche would pair ITMN181 with R7128 or with R1626, Roche’s in-house polymerase inhibitor. With the recently announced demise of R1626 due to toxicity (#msg-33022867), the decision to go forward with R7128 became automatic.

The ITMN-191 + R7128 trial will be watched like a hawk by every player in the HCV arena. I would not be surprised to see other all-oral combinations enter phase-1 even before the outcome of the Roche trial is known.

[DewDiligence]

Re: Tidbits on the all-oral HCV cocktail

ITMN’s Dan Welch gave some tidbits on the INFORM-1 trial of ITMN-191 plus R7128 during today’s DB webcast:

1. The trial sites are in Australia and New Zealand because the FDA (and presumably the EMEA) did not approve of a trial with two experimental agents until each agent was already in phase-2. By mid 2009, each of the agents (ITMN-191 and R7128) will be in phase-2, allowing trials to begin in the US (and presumably in Europe).

2. Two-week results from INFORM-1 should be available in time for reporting at EASL in April.

3. After two weeks on ITMN-191 + R7128, patients will continue with 46 weeks of SoC (a total treatment duration of 48 weeks). Patients will be tested for RVR, EVR, and SVR. (Although two weeks of treatment with ITMN-191 + R7128 may be less than optimal, the above metrics, especially RVR and SVR, will nonetheless be considerable interest.)

4. The exact dosing protocol in the trial is being kept a secret (at Roche’s behest); however, Welch said at least four different ratios of the two drugs will be tested.

5. From the questions by the analysts on the webcast, it’s clear that INFORM-1 is a hot topic among those who follow the HCV arena with even a modicum of interest.