Cure Member Spotlight: Oriana Zinani, PhD

Meet Oriana Zinani, PhD, Co-founder and CEO of Applied PharmacoDynamics, a company developing antibody therapeutics for substance use disorders. A former biotech investor who began her career as a scientist, Zinani brings a rare perspective from both sides of the table. We spoke with her about the science behind APD’s lead program for cocaine use disorder, how her experience as both an investor and operator shapes the company’s strategy, and what it takes to advance a first-in-class therapy in an area with enormous unmet need.

You started your career as a scientist, then became an investor, and now you’re building a company. What led you to starting Applied PharmacoDynamics, and why focus on cocaine use disorder?

I’d say it really was the right people at the right time. I met my Co-Founder, Dr. Andrew Norman, during my PhD training at the University of Cincinnati. Andy has spent decades working on cocaine use disorder, and he and the team built a deep understanding of our lead asset, h2E2. The program had received more than $31M in support since inception. Then, just as it was getting to the edge of clinical trials, the funding unexpectedly fell away.

At the same time, I’d been investing in biotech long enough to build the pattern recognition and confidence to spot a program that truly has a shot. I’ve also always wanted to be a biotech entrepreneur. Like many people in healthcare, I have a personal reason for that: my dad’s death made the impact of diseases very real to me.

So I reached out to Andy, and we decided to form Applied PharmacoDynamics (APD) to advance h2E2 within a company structure. Building it as a company lets us pursue a broader mix of funding sources while staying disciplined about capital and timelines. Cocaine use disorder is a massive unmet need. About 1.2 million Americans struggle with it, and the current standard of care, largely psychosocial counseling, isn’t enough for many patients. Our goal is to develop the first medication that can help prevent relapse.

Your lead program, h2E2, is a first-in-class antibody therapeutic. At a mechanistic level, how does it work, and what makes it fundamentally different from past attempts to treat substance use disorder?

What I love about h2E2 is how intuitive the mechanism is. It is an antibody that binds cocaine in the bloodstream and keeps it from crossing the blood-brain barrier. If cocaine can’t efficiently reach the brain, you blunt its central nervous system effects.

That matters because cocaine is a powerful reinforcer; the “reward” signal is a big part of what drives repeated use. By reducing how much cocaine reaches the brain, we aim to reduce that reinforcing effect and make relapse less likely.

This approach also builds on real human proof of concept. In Dr. Kosten’s anti-cocaine vaccine clinical trial, outcomes improved in patients who generated higher antibody levels. It was a clear dose-response story. The limitation with vaccines is consistency: only some people make enough anti-cocaine antibodies, and the levels can be variable.

With h2E2, we skip that variability by directly administering the antibody. That means uniform protection starting on day one, and the ability to tune dosing. Importantly, prior clinical work gives us a sense of the antibody levels associated with benefit, and with a delivered antibody, we can explore doses that are meaningfully higher, giving us a much larger therapeutics window than past attempts.

Why was an antibody the right modality for this indication, and what advantages does it offer in terms of safety, durability, or clinical strategy?

Stimulant use disorders have been notoriously hard to treat with traditional small molecules. Cocaine affects multiple systems: dopamine, norepinephrine, and serotonin transporters. So it’s difficult to “out-pharmacology” the drug by targeting one pathway and expecting that to be enough.

An antibody lets us take a different angle. Antibodies largely stay in the periphery and don’t easily enter the brain. We use that to our advantage: if h2E2 captures cocaine in the bloodstream, it becomes much harder for cocaine to reach the brain in the first place.

From a clinical and patient perspective, antibodies also offer durability. With their long half-life, the goal is once-monthly dosing, which is a big step up from daily adherence-dependent regimens, especially in addiction, where consistency is often the hardest part.

On safety, the specificity is a major advantage: h2E2 is designed to bind cocaine, not human proteins, which gives us a wide safety margin. In our GLP toxicology studies in animals, we dosed up to the highest feasible level allowed in the study and did not observe adverse effects that we could attribute to the antibody.

Strategically, we’re also not starting from zero. We can learn from prior clinical experience in this area, including Dr. Kosten’s vaccine work, and we’re fortunate to have him on our scientific advisory board as we shape the development plan.

Cocaine use disorder has no FDA-approved therapies despite enormous unmet need. What has building in this space taught you about regulatory, clinical, and investor dynamics?

The biggest lesson is that science isn’t the only barrier, perception is. Nearly one in six Americans struggle with alcohol or drug addiction, yet stigma still keeps many people from seeing addiction as a medical disease. Too often, we “manage” addiction through the judicial system instead of treating it in the healthcare system, which creates enormous costs on both sides.

On the funding side, NIH is effectively the largest investor in addiction. That’s good news: there are meaningful, non-dilutive grants that can support clinical trials. The tradeoff is pace and flexibility. Grant funding can move slower, and it can constrain where and how trials are run.

Investor dynamics are improving but still lag other therapeutic areas. Historically, many VCs avoided addiction because of biology risk, limited precedents, and less big pharma participation. That’s starting to shift. Psychedelics have received significant VC funding, and companies like Tempero Bio have raised significant private rounds. But we still need a clear “win” to pull more capital into the space. 

Regulatory strategy is another reality: with no FDA-approved therapies for cocaine use disorder, you can’t just copy an established playbook. You have to work closely with regulators to define endpoints that make sense for the drug. Done well, that’s not only a challenge. It can be a real advantage. (In myelofibrosis, for example, an endpoint like Total Symptom Score became tightly associated with ruxolitinib, and later drugs often struggled to match it.)

You spent several years investing across public and private biotech markets at firms like Point72, Curie.Bio, and RA Capital. How has that experience shaped the way you think about capital strategy, risk, and execution at APD?

Sitting on the investor side of the table taught me to be honest about two things: where value is really created, and what can genuinely break a program.

First, it’s made me very focused on what data actually changes the story, and how to reach those milestones in a capital-efficient, disciplined way. Not every experiment is worth doing. The goal is to do the work that meaningfully de-risks the program and moves it toward a clear decision.

Second, it trained me to be brutally honest about risk. As an operator, it’s tempting to fall in love with your own asset. My job is the opposite: to constantly pressure-test the science, identify the reasons h2E2 could fail, and build a development plan that gives it the best chance to succeed.

Finally, investing reinforced that time is the most expensive resource we have. Patients deserve urgency, and so do our stakeholders. So I’m always running to get to the truth: do we have a drug here or not? I want to get there as efficiently as possible.

With $31 million in non-dilutive funding and an IND filing approaching, what are the key inflection points ahead for the company?

The heavy lifting to get h2E2 IND-ready has largely been done through about $31M of NIH support. Right now, our near-term focus is completing the remaining IND-enabling work and securing the SBIR support that helps us finish the IND package.

The first major near-term execution goal is an active IND. Once we have that, we can unlock a wave of clinical-trial grant submissions and move from “ready” to “running.”

Clinically, the key early value driver is our planned Phase 1b cocaine-drug interaction study in patients with cocaine use disorder, which we’re targeting to start within the next 2 years. That study is designed to do more than check a box. It should give us an early read on whether the mechanism is translating in humans, including signals that may align with potential registrational endpoints.

The definitive efficacy test will be a randomized, placebo-controlled Phase 2 study, which we hope to initiate within one year of Phase 1b readout. That study is designed to answer the question investors, regulators, and most importantly, patients care about: can this meaningfully reduce relapse in the real world?

As you join the Cure community, what kinds of connections or conversations would most accelerate APD’s mission at this stage?

The Cure community is valuable because early-stage entrepreneurship can be lonely. You’re often making high-stakes decisions with a very small team. Office hours and candid operator-to-operator feedback help me pressure-test our thinking, catch blind spots, and adjust quickly.

I’ve especially enjoyed the sessions with Dr. Shalabh Gupta of Unicycive Therapeutics, Cure’s CEO Seema Kumar, and Dr. Navin Goyal of Loud Capital. I usually walk in thinking I’ll learn one specific thing, and I almost always leave with several different, unexpected takeaways.

Going forward, I’d love to connect with clinical investigators and trial sites experienced in substance use disorders, as well as investors and pharma leaders interested in building the first real medication platform for cocaine use disorder.