CorDynamics Sets Drug Discovery and Development 2013 Trade Show Calendar

The CorDynamics team is saying goodbye to a great 2012 and looking forward to more research and collaboration with colleagues in 2013. Closing one calendar and turning to a new one, some of the first dates to fill in are our trade show exhibitions.

As we continue to grow the early-stage drug discovery side of our business, we will again be visiting the Experimental Biology meeting in Boston, April 20-24. I look forward to attending this event and meeting with colleagues focused on linking drug discovery to development.

In addition to EB, we’ll also be exhibiting at SOT, SPS and ACT.

• Society of Toxicology 52nd Annual Meeting

San Antonio, Texas March 10-14

• 2013 Safety Pharmacology Society Annual Meeting

Rotterdam, The Netherlands September 16-19

• American College of Toxicology 34th Annual Meeting

San Antonio, Texas November 3-6

If you’re going to be at any of these meetings, please put us on your calendar.

Wishing you a very Healthy and Happy New Year.

Theresa Gralinski, Marketing Director

Zofran, The FDA and Return of Cardiovascular Culprit: QT Interval Prolongation

I’m often asked: Why should our project team expend finite resources on cardiovascular safety studies for an oncology therapy or GI compound?

Today’s FDA removal of the highest dose form of Zofran (ondansetron) from the market is a prime example.

Case Study

The gastrointestinal drug ondansetron is a 5-HT3 (serotonin type 3) receptor antagonist indicated for use in the prevention of chemotherapy-induced nausea and vomiting and post-operative nausea and vomiting.

This is an interesting scenario since ondansetron is often used as adjuvant therapy. For example, an oncology patient has nausea and vomiting induced by chemotherapy treatment. Their physician prescribes ondansetron to mitigate these severe GI side effects.  On top of all these issues, one certainly wishes to avoid prolongation of the QT interval. Thus, Drug 1 (cancer treatment) leads to Drug 2 (treatment for the side effects of Drug 1), which is what causes cardiac effects.

Preclinical QT Interval Prologation with Ondansetron

The literature demonstrates that preclinical models are predictive for the electrocardiographic effects of ondansetron. The FDA stated today that the 32 mg, single IV dose should be avoided due to the risk of QT interval prolongation, which can lead to Torsades de Pointes, an abnormal, potentially fatal heart rhythm. Learn more about QT Interval prolongation. 

Our team has published and worked extensively with preclinical models designed to detect the propensity for QT interval prolongation early in the discovery, preclinical and phase I stages. View data.

Serotonin is involved in many areas of human physiology. Drugs that alter the pharmacology of serotonin must be interrogated for cardiovascular effect regardless of the target for therapy.

Timelines and Technology Drive Drug Development

Safety Pharmacology Society 2012 Meeting Reveals the “New Normal”

I’m on my way back from a trade show exhibit at the Safety Pharmacology Society meeting in Phoenix. Four days in the desert were filled with sessions, events as well as many friends and colleagues stopping by the CorDynamics booth to say hello.

It didn’t hurt that my business partner Peter Senese once again claimed the prime booth space—as greeter to all—right inside the exhibit hall entrance. We opened up with a vendor show where we were airing Monday Night Football live. A consistent group enjoyed the game over a beer or two, and shared insight into the current state of their organizations.

New Normal

Attendance was down a bit from previous meetings. The continuing consolidations, mergers, and belt-tightening by nature reduced the size of representation from more than a few companies. Nevertheless, the topic seemed to pass as the ‘new normal’ instead of being the focus as years before.

Positive Signs, Rational Approach to Forward Progress

Clients stopped by to discuss their unique drug development projects. Overall, their questions came down to two general categories.

1. Timelines—When can our new project be initiated? When can we expect results?
2. New Technology—Are CorDynamics’ new technologies generating solid data? How can we incorporate small animal dual pressure telemetry into our studies? Can we screen for cardiovascular liability in guinea pigs?

Leaving the plus 100-degree weather for the tempered fall of Chicago, we’re coming back with good feelings for the remainder of 2012. Happily, new projects continued to flow into the labs during our absence.

We look forward to next years’ SPS meeting in Rotterdam, Netherlands. Word is that Peter already claimed our lead-in booth space. Hope to see you there.

CorDynamics Sets Fall Conference Calendar: Safety Pharmacology Society and American Colllege of Toxicology

With a great summer behind us, the CorDynamics team is looking ahead to a productive fall season and two upcoming trade shows.

2012 Safety Pharmacology 51st Annual Meeting in Phoenix (October 1-4)
With all the recent FDA decisions surrounding cardiovascular safety in everything from weight-loss compounds to hepatitis C therapies, this meeting will be the ideal place to discuss our cardiovascular safety pharmacology expertise with clients and colleagues.

2012 American College of Toxicology 33rd Annual Meeting in Orlando (November 4-7)
We will showcase our safety studies as well as our discovery models to demonstrate our ability to help clients translate preclinical data into greater pipeline predictability.

If you’re going to be at any of these meetings, please put connecting with us on your calendar.

If not, feel free to contact us–we’re always available to collaborate on your most pressing projects.

CorDynamics Sets 2012 Trade Show Calendar

The CorDynamics team is closing out a successful year and setting the stage for 2012. Closing one calendar and turning to a new one, some of the first dates to fill in are our trade show exhibitions.

For the first time, we’ll take our booth to the Experimental Biology meeting in San Diego April 21-25. As we continue to grow the drug discovery side of our business, I look forward to attending this event and meeting with colleagues focused on this exciting and important side of drug discovery.

In addition to EB, we’ll also be exhibiting at SOT, SPS and ACT.

• Society of Toxicology 51^st Annual Meeting

San Francisco, March 11-15

• 2012 Safety Pharmacology Society Annual Meeting

Phoenix, October 1-4

• American College of Toxicology 33^rd Annual Meeting

Orlando, November 4-7

If you’re going to be at any of these meetings, please put connecting with us on your calendar.

Best Regards and Happy New Year.

Investigating the Truth About Afib

AFib, AF, Atrial Fibrillation, — It’s the most common cardiac arrhythmia, affecting millions of individuals. Patients with AF rarely exhibit symptoms and are at a five-fold increased risk of stroke due to thrombosis from stagnant flow in the atrium. With such a target profile, the condition is a hot area for drug developers.

As with many disease states, the path toward targeted efficacy is fraught with hurdles. With AF, one of the long-standing roadblocks has been the selectivity of compounds on atrial vs. ventricular electrophysiology. Usually, the goal is to specifically alter the electrical properties of the heart’s upper chambers (atria) while leaving the lower chambers (ventricles) alone. Not nearly enough new chemical entities have this property—thus, the limited good treatment options in this area.

One way of investigating test articles from both a safety and discovery perspective is to use an instrumented animal equipped to provide information on complete cardiac electrophysiology. These models are effective since they provide a detailed interrogation on these parameters, alongside tolerability and PK/PD information.

For a more in-depth look at how an in vivo model can provide a comprehensive safety and discovery investigation in one experiment, check out our abstract to be presented at the 2012 Safety Pharmacology Society meeting in Innsbruck. We used chronically instrumented dogs to demonstrate the doses of both flecainide and dronedarone that result in changes with atrial, but not ventricular, refractoriness.

Getting to the heart of atrial fibrillation will go a long way in helping researchers make good scientific decisions and drug companies make good business decisions so physicans can guide patients in making the best health decisions.

Pulmonary Arterial Hypertension in Non-Human Primates

My team and I are returning from the 2009 Safety Pharmacology Society meeting in Strasbourg, France. With us was our lead veterinary technician, Ms. Melissa Fisher, who was awarded a Junior Investigator Travel Award for her work with her colleagues developing a model of hypoxic pulmonary vasoconstriction / pulmonary arterial hypertension (PAH) in the cynomolgus non-human primate.

After conducting more than 18 experiments interrogating the intertwining roles of anesthesia, arterial oxygen tension, and surgical plane in the stability of the model, our labs are now providing clients with a paradigm that defines a compound’s ability to selectively reduce pulmonary artery pressure in the presence of existing PAH using non-human primates. Building on our previous work in the canine and rat, Melissa rose to the challenge and coordinated the experiments to bolster the disheartening lack of scientific literature in this arena. There are no reliable publications describing PAH in the non-human primate; only a few aged papers detail measurement of arterial oxygen tension or other tangential parameters having a relationship to pulmonary function in this species.

Looking at the graphs below, we’ve defined the selectivity for prostacyclin (a well-characterized vasodilator) in this model. The experiments could not have gone any better. We previously demonstrated that 10% inhaled oxygen is sufficient to induce a greater than 30% increase in pulmonary artery pressure. At the lowest studied dose of prostacyclin (1.5 μg/kg/min), there was no appreciable reduction in either pulmonary artery pressure or systemic arterial pressure during the hypoxic vasoconstriction.

However, at 15 μg/kg/min, our labs uncovered the differential vasoactivity of prostacyclin on the pulmonary architecture.

As a result of these data, we are highly confident that we can uncover similar properties in proprietary molecules; improvements would likely involve either an augmented differential response or via longer pharmacodynamic action than prostacyclin.

Melissa was excited to accept the award and present the team’s research in France. We believe these paradigms can be of tremendous value as the industry looks toward meeting patient needs in the area of pulmonary hypertension.