CASI Pharmaceuticals Inc (CASI) 2008 Q1 法說會逐字稿

So, we're going to go ahead and get started. As I mentioned the next presenting company is EntreMed Inc. EntreMed is a clinical stage pharmaceutical company, developing multi-mechanism drugs targeting a variety of diseases including cancer.

Presenting for the company is Chief Executive Officer, Jim Burns.

Thank you Ren, and good morning ladies and gentleman and thank you for taking your time to catch up on the progress of EntreMed. I would like to start off this mornings presentation with the usual obligatory statement about forward-looking statements that I might make this morning and the risks associated with those forward-looking statements can be found in our filings with the Securities and Exchange Commission. We are, as Ren said, a public clinical stage company. We have four programs operating right now, they're all in clinical stage of development. We are in -- phase II is our most advanced program of this present time for oncology. And we operate primarily out of Rockville, Maryland.

At the present time, our pipeline consists of four programs, MKC1, which is a cell cycle regulator currently in multiple phase II programs, ENMD1198, which is a new chemical entity derived from our own laboratories which is currently in the later stages of a phase I-B dose escalation all (inaudible) trial. ENMD2076, which is currently in the beginning stages of its phase I-B dose escalation trial -- this is an aurora kinase angiogenesis inhibitor and Panzem, which we had until recently in oncology and we've now converted that program over into rheumatoid arthritis and that has an active IND. And we are in the early stages of its clinical development for RA. We have strong IP surrounding all of these compounds, composition method use patents all the way around. In so in terms of forward-looking developing our own compounds or doing it in conjunction with partners, we certainly have that capability from an IP perspective and we have selectively started looking at individual programs to partner up with Big Pharma or Big Bio.

Now, we have certain historic strengths in the company we have continued to bring those along over the last three years and this is really expertise in angiogenesis, the regulation to cell cycle, cell signaling and inflammation. And we have an experienced management team for this stage of the of the companies development, we will continue to add selectiveIy into the management team to support our growth going forward. CellGene is our largest shareholder and they're about 10%, 12% on a -- on an outstanding share basis. In terms of the pipeline we are currently returning six clinical trials in MKC1, I'll talk specifically about that compound and each of the other ones and once we have finished the phase IB all (inaudible) trial for 1198, we will move into both an extended phase I and phase II program for that particular candidate. With respect to MKC1 this is a cell cycle regulator that was originally developed in its early phases by Roche. It was licensed into Miikana therapeutics, which we purchased at the beginning of 2006. This compound at that time, when it was being developed by Roche was a compound that came out of a CDK inhibitor screen and the mechanisms that were viewed by Roche as being applicable at that present time were the inhibition of important betas, which are proteins that shuttle molecules into the nucleus and the inhibition of micro tubules. Since that time we have now determined that MKC1 is really an m-Tor inhibitor and I will talk a bit more about that. But it's mechanism now, will have a significant roll to play in how we further develop this molecule clinically. Roche had gone through a complete pre-clinical package in vitro and pre0clinical it probably sufficient to drop into an NDA -- when we get to that point. Thorough IP on the compound and we have exclusive world wide license of this compound. There are no claw backs or any other restrictions on our ability to develop on our own or partner this compound out. In terms of its clinical development, there were phase I's and phase II's -- beginnings of phase II's that were conducted by Roche, they saw objective responses in both metastatic breast cancer and non-small cell lung cancer, and some stable disease indications in both pancreatic and ovarian cancer. As part of our license with MKC1, we started off and continued the development of this compound in metastatic breast cancer and in non-small cancer lung cancer. And doing that at the level of the phase I recommended dose from the phase II trials. So, in most of our trials right now we are operating on a two week on, two week off, 125 migs per meter square BID basis. All of the compounds in our pipeline are all orally administered small molecules. That's the consistent aspect of it, in addition to the fact they're multi-mechanism, they have both antiproliferative and anti-angiogenic characteristics.

Within the past six months, we have focused down on what we believe is one of the principle, if not the principle mechanism for MKC1 and what we see is it has inhibitory effects at the richter branch or the m-Tor complex tube portion of the cascade. So, this compound binds m-Tor and interferes with that richter complex and inhibits AKT activation in the PI3 AKT m-Tor pathway. This is a very interesting compound and it's not a (rapid) myosin or a (rapid log). What we think is possible with this compound is that on its own as a, as a first in class richter inhibitor and possibly even in combination with (rapid) myosin or some of the (rapid logs) that are being developed at the present time. We have seen in our preclinical models with this compound -- we've seen some rather dramatic effects. Here is one of them, an ovarian carcinoma model and where we see substantial long term survival. We've also reported on -- on regression in a breast cancer model in combination with Paclitaxel. And we continue to do the preclinical work in support of the clinical development for this compound.

In terms of where we are on clinical programs right now, the metastatic breast cancer, that's closed to enrollment. We've completed that trial, we'll be reporting out the results of this trial shortly, and in terms of other ones, we will be concluding the non-small cell lung -- or being able to report out the interim results on that some time later in the year. We have an AML trial going on in Canada with this compound. And recently we started a pancreatic cancer and ovarian endometrial trial cancer. The latter two trials on the group of trials that are currently underway, the ovarian and endometrial are in direct response to what we now know about the mechanism, the m-Tor mechanism of this compound. And we are also looking at the possibility of schedule changes and looking at a little bit lower dose on a continuous dosing basis. So, this particular trial is also up and running and we are expecting that trial to conclude before the end of the year.

In terms of 1198, this is a novel multi-mechanism compound. This came out of an -- originally an analogging program that we were conducting for (inaudible), the compound is currently in -- in clinical study for rheumatoid arthritis and we were looking to improve the metabolism of what came out of the program was a new chemical entity which had very different, both safety and activity properties. This is an oral stable liquid dispersion. We've got a very strong IP position as the originator of the compound that has very broad applicability in terms of its -- going into many tumor types. We've seen extended survival in both lung and ovarian cancer models and we've seen synergy in combination with (inaudible) and leukemia. As I mentioned we are in the phase I -- latter stages of phase I-B and we had to start at a much lower dose on this particular compound because there was interior species toxicity variabilities but we are now up where we think we are going to see both toxicity and further activity. So, that should be concluding in the second half of the year. In the terms of it's anti-tumor activities in addition to its antiproliferative and anti-angiogenic, it also has an inhibitory effect on transcription factors such as hip 1 alpha, NF (inaudible) B and stat 3 and these particular aspects are -- we are seeing in our multiple animal models at the present time, one of which is shown here in terms of significantly increasing the survival of non-small cell lung cancer models compared to Cisplatin. And this one extending the survival in a acute leukemia model. So, we intend to move forward with this particular compound in both solid tumors and hematological tumors.

In terms of 2076 -- ENMD2076, this is the compound discovered internally within EntreMed. This is a novel oral selective kinase inhibitor that has both antiproliferative and anti-angiogenic properties, it has a unique kinase inhibition profile, there's about five or six key kinases that are important in the activity of this particular compound and from a -- from a proliferative aspect, is the aurora-A is particularly prominent here in about the ten-fold properties over aurora-B (inaudible) and a nice conciliation of angiogenic kinases including (VEGFR), FGFR and PDGFR. We've seen tumor regression in this particular compound in multiple models and we've seen certainly dose dependent inhibition leading to regression in colon breast and leukemia. To give you an idea about what we've seen on a -- on a example in a breast, orthotopic model, at the lower dose shown here we get substantial tumor growth inhibition. But at the 200 migs per kg basis, we see regression in 70% of the animals in the study. And this is what these tumors look like by the time the animals are harvested. You see absolutely a complete absence in the treated animals of any angiogenic properties and substantial shrinkage of the tumors.

And in an MV41, a leukemia model. And, in this particular model what we have done at the highest dose of 150 migs per kg, we see absolute regression. We see a little bit of grow out at the next lower dose of 75 migs per kg. The two lower doses of 15 and 30 migs per kg, we see some inhibitory aspects but not -- certainly not sufficient to generate substantial tumor growth inhibition or regression and at the 72 day mark the animals in the lower doses that had survived we re-randomized those animals and then hit them with the highest dose that induced regression and we had a substantial fall off almost to the level of the original tumor size at the time of the initial treatment. So, what we have seen is in those, those lower doses we haven't seen tolerance to the drug in those lower doses but we have seen continued effect. So, where we are with this compound right now we have started phase I, we are doing the phase I dosing at this inhibition -- dose escalation trial at both Danafarber and the University of Colorado. Its a classic 3 plus 3 dose escalation design and we are looking for -- for PD evaluations of using soluble KDR and cardiovascular monitoring. There have been some issues that have been reported in this class of compounds with some cardiovascular effects but in or IND enabling (inaudible) studies we saw none of that and even in the (inaudible) we saw no cardiovascular effects and we expect this to continue and see this continuing on in our -- in our human trial. So, our goal is to determine an MTD in this particular compound and solid tumor patients. We will start off a hematological dose I-B escalation study toward the end of the year once we've gotten into the first three or four cohorts with the solid tumor.

And the last compound I'll make some comments about is the work we're doing in support of -- (inaudible) of rheumatoid arthritis. We have seen dose dependent inhibition of -- of rheumatoid arthritis in multiple animal models and every one we see the -- similar effects in terms of reducing cellular infiltration, reducing the angiogenic (inaudible), within the tissues, reducing cartive lesions and reducing osteoclast activity and preventing bone reabsorption. And we verified this through multiple blinded immunohistopath in our radio graphic measurements. And when we treat the animals we see almost a complete regression of these four hallmarks of the disease such that you can't tell the difference between treated animals and normal joint-to-joint architecture. And this is -- just shows on the left panel you can see in the vehicle control you see soft tissue swelling. You see break down of the -- of the joint of the animal versus in the (2ME2) treated arm you see basically normal soft tissue in normal joint architecture and the same shows up on histological evaluation. You don't see any of the, of the inflammatory cell infiltration or destruction of the joint. We've moved over into this particular application because it's a need for an oral -- orally administered safe small molecule alternative, some of the biologics, its a very large market, we have a very unique mechanism of action to support this. And ultimately when we get into phase II and phase III trials, they are of substantial size, then we will likely partner this program out.

In terms of where we are from a financial position, we ended '07 with $48 million in the bank. We ended the first quarter with about $44 million in cash. We had $7.4 million in royalty revenues last year. This is from the sales of (thalomid) by CellGene. Now that (Pharmeon) has been purchased by CellGene, and there is EU approval for (thalomid) in Europe on a country by country basis as the countries approve pricing and reimbursement schedules we expect those royalty revenues to increase and we expect this year to probably have in excess of $8 million in royalty revenues on the basis of what's already approved and is scheduled to be approved by the end of year. And we expect the full impact from sale -- European sales of (thalomid) to effect our royal revenue beginning in 2009.

In terms of revenues, usually, we don't record revenues from sales of (thalomid) until sales are over $225 million. But once they trigger on that, we normally book the revenues. So, it's usually in the third or fourth quarter of the year. Once we have the full impact of (thalomid) sales, next year, we should start booking royalty revenues in the second quarter next year. In terms of the milestones that we had for this year, they're a combination of initiating clinical trials and reporting out on the trials that we already have underway. We will report out the results from our phase II metastatic breast cancer trial and phase I and interim phase II data for non-small cell lung cancer. We have initiated already the phase II study in ovarian endometrial cancer. This is a two arm study, one part ovarian, the other part endometriosis. We've initiated the phase I continuous dosing trial and we're hoping to have that completed by the end of the year so we can either report by the end of the year or into the first quarter of '09. And then we are contemplating initiating a combination trial with radiation and MKC1 because we believe it's a radio sensitizer and do that in pancreatic cancer and then report out interim results for our phase I leukemia trial later in the year.

In terms of 1198, the goal is to complete the phase I-B trial in the second half of this year. And initiate an expanded phase I or phase II trial going forward and report out the interim data for the phase I-B once we've established a phase II dose from the phase I study. In terms of ENMD2076 we have a phase I trial in solid tumors under way we will start the phase II trial in hematological tumors later in the year. And our goal here in this particular one -- this is our first program we're looking out to partner with -- with Big Pharma or Big Bio. So, the goal is either last half of this year or the first half of next year, is to secure a partner for this particular program so we can accelerate it's development. Then in terms of Panzem for rheumatoid arthritis, we have already now initiated the normal volunteer trial which we were required to do under our IND and expect to report out data on that later this year. So, we are well on our way and actually ahead of schedule on the RA program. And that basically ends my comments for today. Thank you all for coming, expect to see results from our clinical trials beginning shortly and carrying on through the rest of the year. Thank you for your time and attention.