Replies to post #41985 on Biotech Values

[Biowatch]

OT "for something like anticoagulation, where one needs to fine-tune the degree of the intended repsonse, a target that does not represent a final common pathway or rate-limiting step has the potential to widen the therapeutic index for the desired effect"

It also relates to the "Is it a stroke or brain aneurism?" question that faces people in the ER.

[DewDiligence]

Re: Complexities of the coagulation cascade

By sheer coincidence, Craig Wheeler was talking about this on today’s MNTA webcast.

FXa intervention (Lovenox and other LMH heparins) works great for preventing DVT, but it is ineffective on arterial thrombosis, is not reversible, and is rarely used in the cath lab.

FIIa intervention (Angiomax) works great for preventing arterial thrombosis, but it is ineffective against DVT and impractical for chronic use.

Ordinary (unfractionated) heparin inhibits both FXa and FIIa and is reversible, but it has problems with monitoring and reliability.

MNTA has designed a heparin variant called M118 from the ground up that works on both FXa and FIIa, is reversible, and doesn’t have the monitoring and reliability problems of ordinary heparin. If it works as advertised it will be a monumental blockbuster, but it’s still very early in development.

[DewDiligence]

MNTA Starts Phase-2 Study of M118

[The study will test 600 patients with stable angina undergoing PCI and will use unfractionated heparin as the control arm. Originally, ACS was supposed to be the lead indication for this drug, but that has evidently changed.

M118 is MNTA’s lead proprietary drug candidate. (MNTA’s other programs involve generic drugs or follow-on biologics.) M118 is intended to take the best features of unfractionated heparin, LMW heparin, and direct thrombin inhibitors, while omitting the worst features of each. FXa intervention (Lovenox and other LMH heparins) works great for preventing DVT, but it is ineffective on arterial thrombosis, is not reversible, and is rarely used in the cath lab. FIIa intervention (Angiomax) works great for preventing arterial thrombosis, but it is ineffective against DVT and impractical for chronic use. Unfractionated heparin inhibits both FXa and FIIa and is reversible, but it has problems with monitoring and reliability. M118 works on both FXa and FIIa, is reversible, and doesn’t have the monitoring and reliability problems of heparin. If it works as advertised it will be a monumental blockbuster, IMO, but it’s still early in development.]

http://biz.yahoo.com/pz/071011/128506.html

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Thursday October 11, 9:00 am ET

Ongoing Clinical Program Will Evaluate M118 Across a Broad Range of Treatment Modalities For Acute Coronary Syndromes

CAMBRIDGE, Mass., Oct. 11, 2007 (PRIME NEWSWIRE) -- Momenta Pharmaceuticals, Inc. (NasdaqGM: MNTA ), a biotechnology company specializing in the characterization and engineering of complex drugs, today announced that it has treated the first patient in a multicenter Phase 2 study of the intravenous formulation of M118, the Company's rationally engineered anticoagulant. The Phase 2 study is designed to treat patients with stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The Company also announced top-line results from a Phase 1 study in healthy volunteers designed to evaluate the human safety and pharmacokinetics of intravenously administered M118. The Company plans to present the complete Phase 1 data at a future medical or scientific forum.

Commenting on the M118 clinical program, Robert Harrington, M.D., Professor of Medicine at Duke University and Director of the Duke Clinical Research Institute, stated, ``We're very interested in M118's potential. The data to-date, both preclinical and Phase 1, suggest that M118 may be able to improve upon current anticoagulant therapy in patients with Acute Coronary Syndromes (ACS). The option of utilizing a potent anticoagulant that is easy to monitor and flexible enough to be reversed is very attractive and could be a significant advancement in the management of patients presenting with ACS. However, the potential for M118 to effectively and safely meet this need will only be known as a result of its clinical trial program.'

Phase 2 Trial Details

The primary objective of the Phase 2 trial, known as the EMINENCE Trial (Evaluation of M118 IN pEercutaNeous Coronary intervention), is to evaluate the safety and feasibility of utilizing M118 as an anticoagulant during PCI. The multi-center study is expected to enroll approximately 600 patients with documented stable CAD who are planning to undergo a PCI. Patients will be randomly assigned to be treated with either intravenous M118 or intravenous unfractionated heparin. The study will primarily assess the safety of M118 as well as measures of procedural success in patients with CAD. It is anticipated that approximately 30 centers in North America will participate in the study.

Phase 1 Trial Results

In the first Phase 1 study of intravenously administered M118, Momenta enrolled 36 healthy adult volunteers to evaluate the safety, tolerability and pharmacokinetic profile. M118 or a placebo was administered as an intravenous injection in single ascending doses in six cohorts of subjects. Pharmacokinetic and pharmacodynamic parameters were measured for all dose groups, including point-of-care monitoring via Activated Clotting Time (ACT), which is the most prevalent measure of anticoagulant levels in the coronary catheterization laboratory. No serious adverse events or dose limiting toxicities were reported.

In addition to being safe and well-tolerated in the study, M118 produced rapid, measurable, dose-dependent increases in anticoagulant activity in a linear manner across all study cohorts. An ACT reading of greater than 200 seconds was observed in several dose cohorts, suggesting that an intravenous bolus administration of M118 can produce ACT levels comparable to levels expected with standard heparin doses used in conjunction with PCI procedures and consistent with the recommended Joint ACC/AHA/SCAI Guideline for Percutaneous Coronary Intervention. These M118 doses will be evaluated further in the Phase 2 study. In aggregate, the data generated in this Phase 1 study provide a rationale for initiating the clinical evaluation of intraveneous M118 as a procedural anticoagulant in PCI.

This single ascending dose study was the first clinical trial conducted with intravenously administered M118. The study is part of a broader Phase 1 program that is evaluating M118 via both intravenous and subcutaneous (SC) routes of administration under two Investigational New Drug Applications, and includes single and multiple dose trials and drug interaction studies with agents commonly utilized in the management of CAD. Over 100 volunteers have participated in M118 clinical studies to date.

``It has been very fulfilling to participate in the development of M118, the first novel product candidate to emerge from Momenta's technology platform. The program has made great strides through its systematic clinical evaluation of many of the product attributes that were part of the initial product design' said Ian Fier, Vice President, Development Operations at Momenta and leader of the M118 development program. ``The Phase I study results we're reporting on today indicate that in addition to being safe and well-tolerated, M118 treatment resulted in rapid and measurable anticoagulant activity. In the newly initiated Phase 2 study, we look forward to evaluating M118 in one of its intended therapeutic uses, as a key component of percutaneous coronary intervention.'

About M118

M118 is a novel drug candidate that has been, through Momenta's proprietary technology, rationally engineered to provide anticoagulant therapy to patients with ACS. M118 is designed to interact at multiple points in the coagulation cascade by selectively binding to anti-thrombin III and thrombin, two critical factors in the formation of clots. In preclinical and Phase 1 studies, data have shown that M118 is a potent inhibitor of multiple factors in the blood that lead to clot formation, its effects can be reversed or neutralized and its activity can be monitored. An anticoagulant possessing these properties has the potential to satisfy a currently unmet medical need within the ACS patient population.

About Acute Coronary Syndromes ACS is characteristically used to describe patients experiencing an acute myocardial infarction, or heart attack, as well as patients who present at hospitals with unstable angina, a transient blockage of a coronary artery. According to the National Hospital Discharge Survey, each year in the United States there are more than 1.5 million occurrences of either unstable angina or myocardial infarction requiring medical treatment. As part of the treatment of ACS, anticoagulant agents are routinely administered to prevent the accumulation and formation of blood clots which can lead to serious, life-threatening complications.

About Momenta

Momenta is a biotechnology company specializing in the detailed structural analysis of complex mixture drugs. Momenta is applying its technology to the development of generic versions of complex drug products as well as to the discovery and development of novel drugs. The Company's most advanced product candidate, M-Enoxaparin, is designed to be a technology-enabled generic version of Lovenox(r). Momenta's first novel drug candidate is M118, a rationally engineered anticoagulant specifically designed for acute coronary syndromes. Within the Company's discovery program, it is seeking to discover and develop novel therapeutics by applying its technology to better understand sugars' functions in biological processes, with an initial focus in oncology. Momenta was founded in 2001 based on technology initially developed at Massachusetts Institute of Technology and is headquartered in Cambridge, MA.
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