Replies to post #96689 on Biotech Values

[DewDiligence]

PYMX MNTA: As noted in reply to your post on SI (http://siliconinvestor.advfn.com/readmsg.aspx?msgid=26587522 ), the cumbersome process that’s apparently required for PMX-60056 to reverse Lovenox is a boost, albeit a small one, for MNTA’s M118, which can be fully reversed with protamine (#msg-39146357). I consider this a small boost for M118 rather than a big boost because the target market for M118 is ACS and Lovenox is not a big factor in that market.

[turtlepower]

PYMX - Would the data from this small P1 trial be enough for a company selling LMWH to partner or do you think a PII trial would be required? I assume the surgery efficacy PII trial mentioned in the PR would include patients given Heparin and LMWH.

BTW I'm curious why "healthy subjects" would risk being injected with tinzaparin. I'm guessing the amount was harmless since there was the risk of 60056 not working.

[mcbio]

PYMX - completes Phase 1b/2 for PMX-60056

http://finance.yahoo.com/news/PolyMedix-Successfully-bw-4142698878.html?x=0&.v=1

PolyMedix Successfully Completes Phase 1B/2 Heparin Dose-Ranging Study with PMX-60056 Heptagonist

PMX-60056 Reverses Surgical Levels of Heparin

Re-Anticoagulation achieved, then successfully reversed with PMX-60056

Data will guide dosing for Phase 2 clinical trial in surgical patients

RADNOR, Pa.--(BUSINESS WIRE)--PolyMedix, Inc. (OTC BB: PYMX - News), an emerging biotechnology company focused on developing new therapeutic drugs to treat acute cardiovascular disorders and infectious diseases, has successfully completed a Phase 1B/2 dose-ranging clinical study with PMX-60056, a synthetic small-molecule designed to reverse heparin and low molecular weight heparin (LMWH) anticoagulants. The data from this study shows that PMX-60056 met the study endpoints regarding both the reversal of varying heparin levels, and allowing re-anticoagulation and re-reversal. PolyMedix intends to use these data to support the development of a Phase 2 clinical trial in surgical patients.

Key results from the Phase 1B/2 clinical study include:


•PMX-60056 reversed up to 350 U/kg of heparin. Efficacy in this study was measured by ACT (Activated Clotting Time), a standard bedside measurement. Administration of heparin increased ACT to as high as 574 seconds. In this study, ACT readings for all subjects were at or near normal (100 seconds) in less than three minutes after the end of dosing of PMX-60056.
•PMX-60056 did not interfere with a second anticoagulation. Subjects that were re-anticoagulated with 100 U/kg of heparin followed by a second dose of PMX-60056, showed a consistent response time to the initial heparin reversal.
•PMX-60056 was generally well tolerated with no serious adverse events reported during the study. The most common side effect was a brief reduction in blood pressure that was seen only at the end of some reversals when ACT was already nearing baseline, and only after the last dose of PMX-60056.

The Phase 1B/2 study was designed as an open label, dose titration study to evaluate PMX-60056 in the reversal of surgical levels of heparin, and also in allowing for the possibility of re-anticoagulation. Heparin is an anticoagulant that is commonly administered to patients undergoing cardiac and certain other surgical procedures to prevent blood clots from forming, especially if a cardiac bypass pump is being utilized. After surgery, heparin needs to be reversed, to allow the patient’s blood to clot normally and prevent bleeding. A patient may sometimes need to be re-anticoagulated soon after heparin reversal to allow for additional surgery.

This study enrolled twelve healthy subjects into two cohorts. Each of the subjects received either 200 U/kg or 350 U/kg of heparin, followed 20 minutes later by an initial ten minute infusion of PMX-60056. Subjects then received additional infusions of PMX-60056 until the remaining heparin was fully reversed. Following the first reversal of heparin, a second dose of 100 U/kg of heparin was administered to achieve re-anticoagulation, which was then also reversed with PMX-60056.

“I am encouraged by the promising results demonstrated with PMX-60056 regarding the reversal of heparin, and subsequent ability to anticoagulate and reverse again soon after,” commented Dr. Eric McAllister, Vice President of Clinical Development and Chief Medical Officer at PolyMedix. “We believe the reductions in blood pressure seen in this study are due to an excess of PMX-60056 after the last dose, when most heparin had already been neutralized. This study has provided information that will help us better quantify the dosing of PMX-60056 in our planned Phase 2 clinical trial to reverse heparin in cardiothoracic surgery.”

“The need for a safer alternative for managing coagulation after heparin use in surgery is well understood within the medical community,” commented Nicholas Landekic, President and CEO of PolyMedix. “We believe these results support further study of the use of PMX-60056 in cardiothoracic and other surgical procedures. We are very proud to have discovered this unique compound for development as an anticoagulant reversing agent, and are looking forward to moving PMX-60056 into more advanced clinical studies.”

PolyMedix is planning to initiate a Phase 2 efficacy study in the second half of 2010, subject to regulatory approval. The objective of the study will be to evaluate the safety and efficacy of PMX-60056 in reversing heparin in patients undergoing cardiothoracic surgeries.

About PMX-60056

PolyMedix’s heptagonist compound, PMX-60056, is a synthetic, small-molecule designed to reverse the anticoagulant activity of both heparin and low molecular weight heparins (LMWHs). Heparin is an i.v. anticoagulant used to prevent clots from forming during certain cardiothoracic and orthopedic surgical procedures. After these procedures, the anticoagulant activity of heparin is reversed in order to prevent post-operative bleeding. Protamine is presently the only agent available for this use. Protamine has many limitations, and we believe there is a major need for alternative heparin reversing agents which may be safer or easier to use. LMWHs are used in approximately 12 million patients annually for chronic treatment of thrombosis. Up to 20% of patients may experience bleeding complications. There is presently no FDA approved agent available to reverse the anticoagulant activity of LMWHs. PolyMedix believes PMX-60056 pre-clinical and clinical data suggest potential safety and other advantages over protamine, as well as opportunity to be amongst the first reversing agents for LMWHs.

About PolyMedix, Inc.

PolyMedix is a publicly traded biotechnology company focused on the development of novel drugs and biomaterials for the treatment of serious acute cardiovascular disorders and infectious diseases. PolyMedix uses a rational drug design approach to create non-peptide small molecule drug candidates and polymers that mimic the activity of proteins. PMX-60056, PolyMedix’s lead heptagonist compound, is being developed to reverse the anticoagulant activity of both heparin and low molecular weight heparins. PolyMedix believes that PMX-60056 could potentially be a safer and easier to use anticoagulant reversing agent, with broader activity, than the currently approved therapy for reversing heparin. PMX-30063, PolyMedix’s lead antibiotic compound, is a small molecule that mimics human host-defense proteins and has a mechanism of action distinct from those of current antibiotic drugs, a mechanism which is intended to make bacterial resistance unlikely to develop. PolyMedix plans to develop this compound for serious systemic Staphylococcal infections, including methicillin resistant Staphylococcus aureus (MRSA). Both PMX-60056 heptagonist and PMX-30063 antibiotic are undergoing clinical testing. PolyMedix also plans to continue the development of its PolyCides™, polymeric formulations as antimicrobial biomaterials, which can be used as additives to paints, plastics, and textiles to create self-sterilizing products and surfaces. For more information, please visit our website at www.polymedix.com.

[DewDiligence]

Portola is targeting the same Lovenox-reversal market as PYMX,
although Portola’s program is still in preclinical development.

http://finance.yahoo.com/news/Portola-Pharmaceuticals-iw-1813019709.html?x=0&.v=1

›Portola Pharmaceuticals Announces Investigational Universal Factor Xa Inhibitor Antidote Reverses Anticoagulant Activity of Factor Xa Inhibitors

Findings Presented During Oral Presentation at AHA Scientific Sessions; Elinogrel Data Selected by AHA for "Best of Specialty Conferences" Poster Session

November 15, 2010, 10:30 am EST

CHICAGO, IL and SOUTH SAN FRANCISCO, CA--(Marketwire - 11/15/10) - Portola Pharmaceuticals, Inc. today announced preclinical study results for PRT064445, its universal Factor Xa inhibitor antidote, demonstrating that the agent can reverse the pharmacodynamic effects of anticoagulation by enoxaparin, a low molecular weight heparin, and fondaparinux [Arixtra], both Factor Xa inhibitors, and reduce blood loss caused by these compounds in an animal model. Previously, Portola presented proof of concept data showing that PRT064445 has the potential to act as a universal antidote to reverse the pharmacodynamic effects of all current and novel Factor Xa inhibitors. The new data were presented today by Portola in the "Novel Concepts for Anticoagulation and Fibrinolysis" oral session from 9 a.m. to noon Central Time during the American Heart Association (AHA) Scientific Sessions 2010 in Chicago.

Today, Factor Xa inhibitors are widely used for the treatment and prevention of blood clots. By 2020, they are expected to be used by more than 40 million patients. However, Factor Xa inhibitors can cause clinically relevant bleeding and their anticoagulant activity may need to be reversed in some patients, including those with bleeding-related medical emergencies or those requiring cessation of anticoagulation prior to surgery. No antidote for Factor Xa inhibitors is currently available, and use of procoagulative treatment strategies have potential risks of unwanted thrombosis.

"We are encouraged by the promising results showing that PRT064445 neutralized Factor Xa inhibitors. We believe our recombinant universal Factor Xa inhibitor antidote has the potential to reverse anticoagulant activity in patients treated with current and novel agents in this class of drugs, including our own investigational oral direct Factor Xa inhibitor, betrixaban," said Dr. Daniel Gretler, chief medical officer of Portola.

The preclinical study evaluated the ability of PRT064445 to reverse the anticoagulant effects of enoxaparin, a low-molecular weight heparin, and fondaparinux. Results showed that PRT064445 reversed the anticoagulant effects of both drugs. With enoxaparin and fondaparinux, PRT064445 dose-dependently reversed anti-Factor Xa activity, which is a pharmacodynamic marker of anticoagulation, in both ex vivo and in vitro studies. In addition, PRT064445 prevented the increase in blood loss due to enoxaparin and fondaparinux anticoagulation in an animal model. Previous proof of concept studies have shown that PRT064445 reversed the pharmacodynamic markers of anticoagulation for investigational oral Factor Xa inhibitors, including betrixaban, rivaroxaban and apixaban.

Elinogrel Data Presented at AHA Scientific Sessions

Another Portola preclinical study, "Off-Target Effects at the Vessel Wall, in Addition to Inhibition of P2Y12, Contribute to Bleeding Associated with Clopidogrel and Prasugrel," was selected for presentation during a "Best of Specialty Conferences" poster session. The study findings were presented by Portola today from 9:30 - 11:00 a.m. Central Time. Results showed that in preclinical animal models the thienopyridines clopidogrel (Plavix®*) and prasugrel (Effient®*) caused more bleeding than elinogrel, Portola's competitive, reversible and direct-acting i.v. and oral P2Y12 ADP receptor antagonist in development. These effects of thienopyridines on bleeding were in excess of that observed in mice that lack the P2Y12 receptor, suggesting that some of the additional bleeding observed with prasugrel was possibly due to off-target activity at the vessel wall that was not related to inhibition of P2Y12. These data were previously presented in an oral session at AHA's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference in April.

About Portola Pharmaceuticals, Inc.

Portola Pharmaceuticals develops innovative therapeutics based on targets with established proofs of concept that are designed to provide significant advances over current treatments for cardiovascular disease and inflammation. The company has global development and commercialization agreements with two of the world's leading pharmaceutical companies collectively valued at about $1 billion in upfront and milestone payments plus double-digit royalties on future sales. Betrixaban, its oral direct Factor Xa inhibitor, is licensed to Merck & Co., Inc., and elinogrel, its competitive, reversible direct-acting i.v. and oral P2Y12 ADP receptor antagonist, is licensed to Novartis Pharma AG. Both are Phase 2 product candidates that have best-in-class features to address the global multi-billion dollar hospital, specialty and chronic care antiplatelet and anticoagulant markets. Portola's proprietary pipeline programs are focused on the discovery and development of PRT064445, a novel recombinant protein anticoagulant antidote, known as the Factor Xa inhibitor antidote, to help manage or reverse the bleeding complications in the tens of millions of patients expected to be treated with Factor Xa inhibitors or low-molecular weight heparin worldwide in the next decade; PRT061103, a thromboxane receptor antagonist, which is targeted to address a significant unmet need as a potential aspirin alternative for patients intolerant to aspirin; and PRT062607, a novel, oral Syk-specific kinase inhibitor to treat chronic inflammatory diseases, including rheumatoid arthritis and lupus and certain cancers, including non-Hodgkin's lymphoma and chronic lymphocytic leukemia. It is a part of our broader program based on novel Syk and JAK inhibitors to treat additional inflammatory disease and oncology. For additional information, visit www.portola.com.‹