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November 30, 2009 - 06:11 pm Posted in Featured comments0 Comments

ASH ’09 Sneak Preview

Immediately below is an American Society of Hematology Sneak Preview highlighting some of the more compelling data announcements at this year’s ASH meeting. The information below is brought to you by the publisher of The Medical Technology Stock Letter (MTSL), John McCamant, (www.bioinvest.com). The information published here is not a recommendation, and is provided for informational purposes only.

Although abstracts for the American Society of Hematology (ASH), taking place in New Orleans, December 5-8 have been released, they fail to offer any major insight into the widely anticipated Celgene (CELG) MM-015 study on Revlimid. Both Incyte’s (INCY) and Onyx’ (ONXX) abstracts were of particular significance; and we expect INCY’s JAK-2 inhibitor, INCB018424; and ONXX’ carfilzomib (Proteolix) to both deliver game changing data. In fact, INCY’s 18424 has already been significantly validated by the huge partnership inked with Novartis last week. The key for these names will be presenting fresh Phase 2 data that will instill confidence in both company’s on-going Phase 3 programs. Other MTSL recommendations that will be at ASH include ImmunoGen (IMGN) and Allos (ALTH).

Allos has announced that four abstracts from studies of Folotyn were accepted for presentation. Presentations will summarize new analyses of data and updated efficacy results from the company’s pivotal PROPEL study, which served as the basis for the FDA’s accelerated approval of Folotyn on September 24, 2009, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). In addition, there will be a poster summarizing results of a Phase 1 study of Folotyn in combination with gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies, and an oral presentation highlighting results of a multicenter, dose-finding study of Folotyn in patients with cutaneous T-cell lymphoma (CTCL). The posters are important as they are part of the process of educating oncologists about the benefits of Folotyn. But probably most important from a stock point of view is that potential partners/acquirers will be in attendance. The drug remains unpartnered and has to be on the radar screens of many companies that are looking for new drugs. Given the recent INCY/Novartis deal we feel that some of the spurned bidders for INCY’s drug candidate are now exploring a deal with ALTH.

Celgene. Recently, it was reported that CELG has been having ongoing conversations with the FDA and EMEA regarding the MM-015 trial. It appears that the company might be able to present unblinded data at ASH from all 3 arms from MM-015 study based on 50% events. Positive data would be important as the top-line results announced last July demonstrated a statistically significant improvement in progression-free survival over treatment with chemotherapy alone. The primary concern from Wall Street is that the benefit of Revlimid maintenance won’t outweigh Revlimid induction, as more Revlimid is used in maintenance therapy.

ImmunoGen has momentum going into ASH as they recently reported encouraging clinical data from its IMGN901 drug development candidate for the treatment of Merkel cell carcinoma (MCC). These findings were reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. A total of six patients with MCC have received IMGN901 to date. All of these patients had received prior chemotherapy regimens for their cancer and entered the clinical trial, Study 002, with metastatic disease. Two of these six patients had a marked, objective response to treatment with IMGN901, while a third patient had clinically relevant stable disease for this patient population

IMGN901 has been designed to kill cancer cells that express CD56, a protein. It consists of a CD56-binding antibody with the company’s potent cancer-cell killing agent, DM1, attached to it using an engineered linker. IMGN901 is a potential treatment for MCC, small-cell lung cancer (SCLC), multiple Myeloma (MM), ovarian cancers and other CD56+ tumors.

IMGN will have additional data at this week’s ASH as IMGN901 is also being evaluated for the treatment of CD56+ MM. Study 003 evaluates the compound when used as a single agent to treat MM patients that have progressed on prior therapies despite being heavily treated (mean prior therapies=6). The maximum tolerated dose was recently established in this trial as well, and patient enrollment is underway in the expansion phase. Some of this data will be presented at next month’s ASH meeting. Study 005 will evaluate IMGN901 for MM when used in combination with Revlimid and dexamethasone. This trial is expected to start later this year.

Also at ASH, we will see the first dataset for SAR3419, a CD19-binding antibody with the DM4 payload attached. The drug candidate showed impressive efficacy (3CR/2PR) in a Phase 1 trial in Rituxan-refractory NHL (mean prior therapies = 4). SAR3419 is licensed to Sanofi and represents another drug development candidate that has the potential to add to the company’s overall value, as the IMGN investment story is clearly more than just T-DM1.

InCyte The Phase 1/2 data for INCB18424 in polycythemia vera (PV) and essential thrombocytosis (ET) will show treatment affects after three months of dosing for all patients. The abstract shows 34 patients treated for three months, with 20 having been treated for six months. 94% of these patients had a PR or CR. Exaggerated JAK2 signaling is believed to play a dominant role in PV and ET by driving unchecked differentiation and proliferation of red blood cell and platelet precursors. Thus, the endpoints will focus on the reduction in cell count of red blood cell and platelets, splenomegoly, and disease symptoms such as pruritis. We expect positive results based on management sentiment and the higher frequency of JAK-2 mutation in PV and ET than in myelofibrosis (MF), an area in which 424 has already shown proof of concept. Additionally, INCY will provide an update of the ongoing Phase 2 study in MF. The average exposure to drug is at 1.5 years in this trial, with at least 80 patients having been treated for that long. The other oral presentation will focus on early Phase 2 testing being done at the M.D. Andersen cancer center of 424 in refractory AML patients.

We expect 424 to be one of the big winners at this year’s ASH as the combination of data is very impressive. We also think that many analysts have been underestimating the market potential for 424 by focusing on the MF market which is 14,000 patients in the U.S. While 14,000 patients is a decent sized market opportunity, the markets for PV (95,000) and ET (80,000) in the U.S. have the potential to get Wall Street analysts to significantly increase their estimates for 424’s potential. In addition, INCY estimates these same markets in Europe are 1.5 times larger than in the U.S. Thus, the combination of the three diseases in the U.S. and Europe adds up to a substantial cancer opportunity. The higher frequency of JAK-2 mutation in PV and ET patients than in MF also adds to our confidence that the data will be positive. We expect INCY to have a strong presence at ASH and the stock price to move higher.

Onyx has announced nearly 20 presentations at ASH evaluating carfilzomib and ONX 0803 (SB 1518) in hematological cancers. Among the data presentations are four oral and seven poster presentations highlighting data from the carfilzomib development program in patients with relapsed and refractory multiple myeloma (MM). Carfilzomib data hi
ghlights include:

  • Updated Results of Bortezomib-Naive Patients in PX-171-004, an Ongoing, Open-Label, Phase II Trial of Single-Agent Carfilzomib (CFZ) in Patients with Relapsed or Refractory Myeloma (MM)
  • PX-171-004, an Ongoing Open-Label, Phase II Study of Single-Agent Carfilzomib (CFZ) in Patients with Relapsed or Refractory Myeloma (MM); Updated Results from the Bortezomib-Treated Cohort
  • Phase Ib Multicenter Dose Escalation Study of Carfilzomib Plus Lenalidomide and Low Dose Dexamethasone (CRd) in Relapsed and Refractory Multiple Myeloma (MM)
  • Carfilzomib (CFZ), a Novel Proteasome Inhibitor for Relapsed or Refractory Multiple Myeloma is Associated with Minimal Peripheral Neuropathic Effects


ONX 0803 (SB1518) data highlights include:

  • Phase I Study of the Novel Oral JAK-2 Inhibitor SB1518 in Patients with Relapsed Lymphoma: Evidence of Clinical and Biological Activity


The company has done a very good job of creating a pipeline behind Nexavar and this year’s ASH is their chance to show it off. We seen some of the carfilzomib data before the acquisition and have been impressed. The ability to work in refractory MM is very important as it is the best shot at gaining approval given the multiple choices front-line MM patients already have. The refractory market is larger than one might expect as unfortunately all MM patients will eventually relapse as they become refractory to drug therapy.


November 04, 2009 - 07:11 pm Posted in Featured comments0 Comments

In a new feature for OBR readers, we will occasionally get updates relevant to recent oncology headlines or upcoming oncology events from John McCamant, publisher of The Medical Technology Stock Letter (www.bioinvest.com). The information published here is not a recommendation, and is provided for informational purposes only.

GenVec’s stock is up as much as 25% this morning on news that the FDA has given “Orphan drug” designation to TNFerade for the treatment of locally advanced pancreatic cancer. The most important aspect of Orphan drug status is that it provides seven years of market exclusivity after a drug is approved. The news serves as a reminder that TNFerade is a Phase 3 cancer drug development candidate that will address a protected market. Orphan drug status also makes it easier for a potential partner to pull the trigger as they can view TNFerade as a having at least one protected market opportunity. The drug candidate is also being tested in several other hard to treat cancers; head and neck, rectal, and esophageal. When one combines these markets together, it makes it easier to see how a potential partner would be able to leverage the technology to create multiple revenue streams. We met with management last week at the BIO Investor conference and the company is clearly growing more optimistic with the TNFerade PACT trial finally maturing. A planned interim analysis is expected to occur this quarter when the 184 events (deaths) have occurred in the trial. The data then would be announced roughly 10-12 weeks later, after the data has been cleaned, which we would expect to occur sometime during the first quarter of 2010. While we do not expect the trial to be stopped prematurely, once the interim has been passed smoothly, a partnership may materialize before PACT concludes. Our optimism for a partnership is based on two points. The first is the next interim look should provide additional info on TNFerade’s safety and efficacy making it a more desirable partnership candidate. Second, is the fact that there remains a dearth of late-stage cancer drug development candidates that are unpartnered. Thus, our confidence is growing that the combination of these factors may lead to a partnership for TNFerade before PACT concludes. The stock has periodically traded as high as $1.00 and as of 2PM EST was trading at $0.89.

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