Objections

The last week has been disappointing and inspiring. All the operational tasks are going fine. The difference has been the conversations I had with doctors and patients. Although only a handful of each, I've learned a lot.

I've worked through many, many scripts. And a week ago, I was confident I had the right tone and message to explain to people with PD and the experts how the data showed we could conquer Parkinson's with a new approach.

The example I used was from work in the early 1990s when Glaxo (it started with the pharmaceutical company Smith Kline & French working with Boehringer Mannheim, neither of which exist today) were developing a beta-blocker for heart failure, which was contraindicated and counterintuitive back then. They gradually won over the skeptics.

Later I experienced it when I pushed back against a drug that Johnson & Johnson purchased for $2.4B. Despite widespread excitement and forecasts for huge sales of the drug, I saw reason to be concern. It was a lonely project but eventually the data won and the drug is no longer on the market.

So I felt prepared to convince patients, experts and funders that a major change in Parkinson's treatment strategy made sense.

But I was not prepared. This week, I failed again, but in doing so I believe I've learned important lessons.

1. Changing the view of an expert takes time. I spoke with an internationally recognized Parkinson's expert to give him an update on Right Brain Bio's progress. I first spoke with this person 5+ years ago. Their response? They complemented the major progress and asked if there was a way they could help. Then, there was an interesting disclosure: "the first time we spoke I thought you were nuts."

2. People, companies and systems are scared of change. Many have discussed and written about this. I discussed the plans of Right Brain Bio with a very well educated person with Parkinson's. He were enthusiastic on the need for innovation - acknowledging the disappointment of currently available therapy. Other patients were brought into the conversation - each dubious. The group convinced him that the Right Brain Bio approach was the wrong one to pursue. When I asked him why he seemed to have changed his mind, he tole me he was scared that I could be right as that would mean he had been taking the wrong medicine based on the wrong approach for years. The fear drove his view.

3. Don't expect it to be easy to change minds. When I read about the work of Nobel winner Daniel Kahneman and his colleague Amos Tversky, I believed I was ready to change minds. They taught to account for the fear of loss associated with change as a stronger force than the potential for gain. I figured it would be straightforward to highlight the losses faced by a person with PD who is limited to continued dependence on dopaminergic drugs. These are important, high impact therapies. But the data show they are temporary answers and come with their own risks. But the patient conversations this week showed me that data are not enough - there is a strong commitment to these available dopaminergic therapies. I need a new approach. My effort to reverse beliefs seemed to push these patients (and doctors) to defend their views - essentially making it harder to change their minds. I was trying to make too big an impact too quickly. I can't expect people to shift their beliefs to the opposite viewpoint. I need to move more slowly.

4. Emphasize need for additional testing rather than conquering the disease (even though I believe that the data suggest this drug could conquer the disease). This week, I shared with a neurologist how the data show a path to conquering Parkinson's. His response was to immediately and exhaustively point out that there were no data to support such treatment. After all, he noted, there are no clinical trials or published clinical experience. And rightfully he emphasized my own statements about the currently marketed version of the active ingredient in RB-190 (the drug we are developing) are so high that I expected using it would hurt people. Even when I tried to shift back to the merits of conducting a clinical trial - it was too late. He heard me claim the drug will conquer the disease - even though I was careful to select my words to communicate my believe that the clinical trials could show that the drug worked.

So what do these recent experiences mean?

• Lead with uncertainty: state clearly and simply that current therapies are not enough. Everyone will agree with that.
• Present the science: there is a new mechanism with enough preclinical data to support testing. Here too it is hard to disagree.
• Describe the next step without overreach: a clinical trial will test whether targeting this new mechanism can change clinical or biologic measures of disease.
• If asked about the mechanism, discuss the trial design that minimizes risks: the purpose is to identify the right dose of the drug and that the FDA agreed it was designed adequately to minimize the risks to people who enroll.

By purposefully avoiding the perception that I am overreaching, a patient and/or an expert would be more likely to agree with the plan. It's not changing what I want to communicate but it could change how the listener responds.