Quella che segue è la trascrizione fatta da seekingalfa.com della parte relativa all'SB-728-T.
- Our therapeutic product, ZFN Modified Autologous CD4 T-cells is called SB-728-T. Thus far results from Phase I studies of this product have been very encouraging. The data demonstrated this. Statistically significant relationship between the level of engraftment of ZFN-modified cells in which both copies of the CCR5 gene disrupted, so-called biallelic modification, and the level of virus in the blood of HIV infected subjects during a treatment interruption from antiretroviral medication.
This observation is consistent with the hypothesis under which we began this program and with this clear early signal, at the beginning of the year, we moved quickly into two Phase II studies. The first trial, Cohort 5 SB-728-902 exclusively enrolled HIV infected subject that already carried a natural mutation, CCR5 delta-32 on one of their two copies of the CCR5 genes. These individuals, heterozygotes, the CCR5 delta-32 comprise approximately 5% to 10% of the population of HIV infected individuals in the U.S.
Competitive individuals with neither earlier modified as they already have one copy of the CCR5 gene disrupted by the natural mutation, treatment with our ZFNs results in roughly a doubling of the numbers of biallelically modified T-cells. This Phase II study follows up on an observation made in an earlier Phase I trial in which we measured a reduction in viral load to undetectable levels in a 728-T treated CCR5 delta-32 heterozygous individual during a treatment interruption or TI of the anti-viral medication. That individual although with undetectable viral load at the end of the TI is required as part of the protocol to go back on to heart.
Our new Phase II trial is structured so that a longer period of TI can be monitored, up to 20 HIV-infected CCR5 delta-32 heterozygous who are on HAART maybe enrolled in the trial. These subject to treated with 728-T and eight weeks later undergo a treatment interruption where they discontinue their HAART for a period of 16 weeks. If their viral loads decrease to undetectable levels they may remain of their HAART for as long as this affect assists enabling us to measure the durability of such a response.
When we began this study, we were uncertain as to the availability of subjects for this trial. As I’ve said before that represent only 5% to 10% of the HIV infected population in the U.S. However to date the challenge of enrollment in this study has been reduced as many HIV infected individuals are aware of the CCR5 gene status.
Our second trial SB-728-1101, which is applicable to the other 90% to 95% of the U.S. HIV infected population, was initiated later in the first quarter. This Phase I/II study employ the lymphopenic preconditioning regimen with the drug called Cytoxan intended to expand the numbers of biallelically modified cells in subjects post infusion. This preconditioning regimen, which temporarily reduces the number of lymphocytes in the body results in an increased in the levels of T-cell growth factors stimulating the remaining immune cells to rapidly expand and divide, so if we infuse 728-T immediately after preconditioning, we expect a significant increase in the numbers engrafted biallelically modified cells, potentially by orders of magnitude.
In this study, just prior to infusion of 728-T, we are pre-treating each subject with a dose of Cytoxan. Again, there is a 16 week TI built into the study, which begins six weeks after 728-T treatment and can be extended if subject obtained an undetectable viral load. This strategy has been previously used in individuals with HIV in a variety of settings.
However, as we are combining this with 728-T treatment, I need to explore the dose required for optimum pre-conditioning. We are carrying out a dose escalation phase of three dose cohorts each with three subjects per cohort. Dose escalation studies are frequently designed to include observation periods both between subjects enrolled into the trial and initiation of a new dose Cohort. And so, they generally take longer than a non-dose escalation trial of a similar size. In this study, we are required to wait for two weeks after the treatment of the subject before we treat the next subject in that Cohort. After the treatment of the final subject in the Cohort, we need to observe and collect data for four weeks and then present our findings to the Data Safety Monitoring Board before advancing to the next dose Cohort.
Thus while enrollment is progressing well in both of our studies, these trials would take time. We therefore expect to present preliminary data from all of the subjects in the first half of 2013 and a complete data set in the second half of 2013. As usual, we expect to present the data at a major medical meeting.
Consistent with that approach, I’m pleased to announce today that we have been notified the two abstracts have been accepted for presentation at ICAAC in September. These presentations will focus on important immunological analysis and methods for evaluating the [profile] reservoir from our earlier Phase I trials.
(...)
Charles Duncan – JMP Securities
And congrats on the good progress. Edward thanks, heterozygous study Geoff mentioned that going into you were a little bit concerned about, whether or not patients knew their standards. Yes, he said that the challenge has been pretty much reduced. Can you provide a little bit more color on that? And second, fairly he also outlined nicely that kind of rate limiting steps and the second study to enrollment and trial completion. I am wondering if you could provide that for that state for the heterozygous study?
Edward Lanphier
Yeah. So, Charles I’ll go a little bit on the first piece, and Geoff and Dale again can add or subtract to my comments. And then, I think I missed the second part. So maybe we can come back to that, but in terms of the accrual processes, I think I have mentioned several times, and when we started this study, given that the estimate of delta-32 HIV-infected subjects in the U.S. is in the 5% to 10% range, it was uncertain how difficult or not this trial would be to accrue and one of the observations that we’ve learned as we initiate this study was a, sort of surprising number of HIV subjects who did know their CCR5 status, and because of that we did have people showing up at the site saying, hey, I’m a [homo] delta-32.
So it ended up being, at least today, a more efficient process than maybe a worst-case scenario might have anticipated. Geoff or Dale any other thoughts about that part of the question?
Geoffrey M. Nichol
No that’s pretty much itself, I mean we thought, we could get seriously enough with very, very few patients by the time we looked to their entry criteria and dealt with the CCR5 heterozygote issue requiring us to screen hundreds or thousands of patients in order to get the patients in, and that has not been set back. Nevertheless, we are making good progress with recruitment on both of the studies, you asked about the second study and that is very much just a timetable issue, we just are recruiting well, but we simply have to wait between patients and between cohorts. So it sort of it steps forward in a measured fashion.
Charles Duncan – JMP Securities
Yeah, that part I understand. I’m sorry for miscommunicating. What I was really asking is if you could outline for the actual conduct of the heterozygous study, if there are any rate-limiting steps to the conduct of that as you did nicely for the lymphodepletion study? And then with regard to that heterozygous study, the knowledge of whether or not patient is dealt as a heterozygous. I’m wondering if that has changed your perspective on the percentage of those patients in the population and if that selects for certain patients in terms of social economic status or anything?
Edward Lanphier
On the first question Charles, no, there are no analogous rate-limiting steps in the heterozygous study, (inaudible) dose escalation timeframes associated with the, as I talk some studies. So I know, there are no timing or gating items like that in terms of learning’s about the demographics or so on delta-32 subjects is there anything that Dale or Geoff you comment on that.
Geoffrey M. Nichol
No, Charles again, I mean we are dealing with relatively few site sale, obviously have lot catchments in really quite – in their own geographical areas, and really there is nothing that we can really derive from that data that would speak to the broader epidemiological question you ask?
(...)Ted Tenthoff – Piper Jaffray
Excellent, thank you very much for taking the question. And I appreciate very much the detail on the revenue side as we’re starting to see progress from Sigma and the details on the Shire deal. One quick question. I apologize if this is a bit dated, but are you still enrolling Cohort 5 from the Phase I study and will we get an update on that data or is the primary focus on the Phase II studies now?
Edward Lanphier
So we initially – I’ll start here. We had four cohorts in that study. The Cohort 5 of that trial, that 902 trail is this delta-32.
Ted Tenthoff – Piper Jaffray
Phase II.
Edward Lanphier
Yeah, is the delta-32 trial.
Ted Tenthoff – Piper Jaffray
Okay. So that’s what it’s become. Okay, excellent. That’s really helpful. And, so that’s the data that we will get interim results from both of the Phase II and the first half and full data by year end next year is that correct?
Edward Lanphier
That’s absolutely correct.
