Jonathan Aschoff: Okay. So as far as the primary efficacy endpoint for this trial is concerned, the only thing mentioned on clinicaltrials.gov is in light of any efficacy endpoint is resist ORR. So is that the endpoint here because you are talking about following patients who are often the most of whom are off drug for PSS. But there is no mention of primary endpoints in your slides in the clinicaltrial.gov site, what is the primary endpoint for this U.S. STS LM trial?
Walter Klemp: We are looking at progression-free survival. I would point out again that we €“ this is not €“ this is highly unlikely this is going to be a pivotal trial, the final pivotal trial, this is going to be the hopefully the next to the last. So, from our perspective, we are looking at everything. We are evaluating all endpoints. And when we finish our analysis of all the endpoints ourselves with key opinion leaders then go to the FDA, we would then determine what’s going to be our primary endpoint after determining who our patient population will be. So, it is too early to definitively state what’s going to be our primary endpoint in our final trial. That’s why we’re doing this trial. We are doing this trial to identify the patient population with dosing and the endpoint.
We have already identified the dosing, we found it’s 330 milligrams per meter squared. And now we are continuing on to identify the patient population and the endpoint for the next and hopefully final trial.
Jonathan Aschoff: Okay, the last two, the first one is quick, can you tell us the low dose used in Cohort 1 of the EU STS LM trial? That’s a short one. And can you be in any way explicit about this anthracycline cardiotoxic paper, explicit regions of that paper that you might want to draw people’s attention to?
Walter Klemp: As far as the European study that is an investigator sponsored trial. We are not running that trial, the investigator is €“ the dosing is entirely different. We do once every three weeks. They are doing more of a daily for consecutive days. So, they are starting because it’s daily at a very low dose of I think its 30 milligrams per meter squared. And they are it’s a Phase 1 dose escalation. They are going to be increasing the dose. So, it’s going to be very difficult to compare their dosing regimen to ours initially. As far as the cardiac toxicity paper, it was a review of all of cardiac toxicity and anthracycline therapy. What I would say to define our cardiac toxicity, I think I mentioned when I was describing where we are that we have methodically looked for cardiotoxicity.
We have done that by doing sequential measurements of a certain €“ of certain enzymes troponins which when the heart is damaged these go way up. We €“ and they go up, they stay up, we have not seen that. More importantly, the ultimate cardiac toxicity with anthracyclines is they don’t damage the electrical system. You can think of the heart. It’s two different things in the electrical system that makes the heart contract, and it’s the muscle the pump that pumps the blood. What anthracycline do, they impair the ability to pump. Most of us with a healthy heart 65% roughly of the blood in the heart is pumped out into the aorta with each pump. Two-thirds of the blood is pumped out each time with anthracyclines is the dose, the accumulate dose goes up this starts to fall.
