Trofinetide

Acadia CEO Catherine Owen Adams, Acadia Pharmaceuticals More than thirty years since its 1993 founding, Catherine Owen Adams and Elizabeth Thompson—the R&D combo that has led Acadia since last summer—are managing two products on the market and a pipeline estimated to be worth an additional $12 billion in sales. After 32 years in business, Acadia Pharmaceuticals recently held its first-ever R&D Day, forecasting a potential $12 billion in annual sales stemming from its investigational pipeline. “We’re a small biotech now, but we have aspirations to be a biotech powerhouse,” CEO Catherine Owen Adams told BioSpace . When Owen Adams joined Acadia last September, her first priority was to “stabilize” the commercial business, which she said has now been done. Her second priority was “redefining [Acadia’s] strategy moving forward. Where are we going? How big could Acadia be?” With two products on the market—Nuplazid for Parkinson’s disease psychosis and Daybue for Rett syndrome—and seven experimental assets in clinical and preclinical studies, the company believes the entire package could be worth $14 billion in annual revenue. This highly touted pipeline also has a new leader. Elizabeth (Liz) Thompson joined the company as head of research and development a month before Owen Adams after a stint as Amgen’s EVP of R&D, rare disease “Previously, there’s been a little bit of reticence about showing too much of the pipeline,” Owen Adams said, “and I think Liz and I really challenged that and wanted to show some of the more exciting nearer-term opportunities and also some of our new thinking about how we’re going to partner, how we’re going to focus.” Owen Adams defines Acadia as a neurological and rare disease company—notably, one largely targeting symptomatic treatments for neurodegenerative diseases. The pipeline includes two assets in mid- to late-stage studies for hyperphagia in Prader-Willi syndrome, Alzheimer’s disease psychosis and lewy body dementia with psychosis. This focus places Acadia squarely at the center of an emerging trend that also includes Bristol Myers Squibb, AbbVie and Neumora Therapeutics : the holistic treatment of Alzheimer’s disease. “Whilst memory loss is upsetting and difficult, the psychosis and . . . agitation . . . they’re really, really disturbing for families, and it means that caring for that patient becomes incredibly hard at home,” Owen Adams said. “One of the main reasons that patients are admitted to long-term care facilities is not actually their . . . memory loss, it’s their psychosis or agitation, so I think there will continue to be a lot of focus.” First approved in 2016, Acadia’s Nuplazid (pimavanserin) was the first—and remains the only—FDA-approved treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. ACP-204, currently in Phase II trials for Alzheimer’s disease psychosis and lewy body dementia with psychosis, is a follow-on compound to that drug, Owen Adams said. At its marketed dose, pimavanserin is not associated with the heart rhythm disorder long QT syndrome, she explained. However, once that dose is raised, a QT signal is identified, “which in the elderly, is not great.” This has prevented Acadia from dosing pimavanserin at the higher levels that would be required to optimally treat these other indications, Owen Adams said. “So we redesigned ACP-204 to have little or no effect on QT prolongation,” which has enabled the company to double the dose of currently marketed pimavanserin to achieve a stronger response in clinical trials. BMO Capital Markets analysts were bullish on ACP-204, saying in a June 25 note to investors that it could “provide key improvements” on pimavanserin’s pro mitigating concerns over QT prolongation, enabling higher dosing and allowing for a faster time of onset. This is one of the compounds Owen Adams is most excited about—partly for personal reasons: each of her parents is afflicted by one of these two diseases. “Just from a personal perspective, I understand the devastation it causes for families,” she said. But like any proud parent, Owen Adams didn’t want to pick just one high-potential asset. She also highlighted ACP-101 (carbetocin nasal spray), currently in Phase III studies for hyperphagia in Prader-Willi syndrome, a rare, neurobehavioral genetic disorder characterized by severe, life-threatening hyperphagia—an abnormally great desire for food—metabolic issues and intellectual deficits, among other behavioral issues. Acadia picked up ACP-101 in its $10 million acquisition of Levo Therapeutics in 2022. In a Phase III trial conducted prior to the transaction, 3.2 mg of the drug demonstrated “nominally statistically significant efficacy,” and was safe and well-tolerated, according to a June 2023 press release from Acadia. Still, the FDA rejected Levo’s application for the drug in January 2022, recommending another trial to confirm benefit. ACP-101’s history is part of the draw for Owen Adams. “Just because it came from a failed Phase III study, a $10 million outlay [and] really a lot of skepticism around the science and the focus,” she said. Acadia accelerated recruitment for the Phase III trial and pulled forward the timeline for topline results from 2026 to the fourth quarter of this year. “I’m really excited for that one because I think it could be a real game changer,” Owen Adams said. BMO had a different selection, however. In their June 25 note, the analysts said they “are most optimistic about the potential of ACP-211 (being developed for treatment-resistant depression and major depressive disorder) given validated success of [J&J’s] Spravato [esketamine] in MDD.” ACP-211, an orally administered, deuterated form of R-Norketamine, is currently in Phase I trials, with a Phase II study expected to begin in the fourth quarter . Back on Track While Owen Adams expressed optimism for Acadia’s future, she acknowledged the path hasn’t always been a smooth one. In March 2023, Acadia’s Daybue won FDA approval as the first therapy for Rett Syndrome, a rare, neurodegenerative disorder primarily affecting girls. Then, after about nine months, the company began to hear reports of gastrointestinal side effects on the community. “We got off to a great start, strong support from our rep community,” Owen Adams said. Then “we had a pretty difficult 2024 with flat to declining patients.” At the same time, Acadia learned more about how to leverage a titration approach to better manage those GI side effects and has since undertaken an educational campaign with patient families. “And now we’re back to growing patients again,” Owen Adams said. Acadia’s focus on diseases that affect small numbers of people isn’t the biotech’s only rarity. The company is also led by women in key positions. “I think Liz and I are actually the only CEO/head of R&D all female combo,” Owen Adams said. She and Thompson are joined by Chief Legal Officer Jennifer Rhodes and Chief Medical Officer Ponni Subbiah. “I think what it does give us is that diversity of thought and experience and energy,” Owen Adams said. She also pointed to the fact that she and Thompson are new to the Acadia team. “I think that energy is important in biotech, because you come in and you really want to make a difference, and you really want to ensure that we’re on the right track, and I think that is definitely evident right now.”

Acadia Pharmaceuticals, the brain-focused drug developer, surprised some on Wall Street last week with a pair of predictions.The first: the companys two products, which brought in close to $1 billion in 2024, should eventually generate between $1.5 billion and $2 billion in combined yearly sales. The second: five experimental medicines in Acadias research pipeline could, if they come to market, collectively peak at $12 billion in annual sales.The road to such commercial success will be long and fraught, as neuroscience is a famously difficult, setback-ridden area of development. But Catherine Owen Adams, the industry veteran who took over as Acadias CEO last fall, maintains the company is up to the challenge.I didn't come into this job to putter along at a $3 billion market cap, she said in an interview. I believe this company can get to the next level of mid-cap. That's how I'm leading this business to get there.To reach that goal, Owen Adams said a top priority for her team is further building out Acadias research, through a much more assertive business development strategy. That may include deals for drugs in the later stages of testing the kind of assets that can serve as the value inflection point analysts have sought.The hope, according to the chief executive, is Acadias pipeline will grow at least 25% to 30% from external innovation in the coming years, and that $12 billion figure bumps up to $15 billion or $20 billion as a result.Owen Adams spoke to BioPharma Dive about why Acadia offered up such bold sales forecasts and where the company believes it can play to win in brain research.The following conversation has been edited and condensed for clarity.BIOPHARMA DIVE: Neuroscience is a wide area of research, and your pipeline reflects that. Acadia is going after two rare diseases, Alzheimers psychosis, depression, epilepsy. Why did the company decide to target those indications?CATHERINE OWEN ADAMS: When I came to Acadia nine months ago, part of the attraction was the pipeline. A lot in there was super interesting. I spent the last six to seven months with [research and development head] Liz Thompson trying to understand what we're trying to achieve. What's our focus?The brand we are developing is underserved neurological and rare diseases. Underserved is actually quite an important descriptor of those two areas, because we're not going to move into Alzheimer's degeneration. It's just too big for us.However, the areas around that, where there are maybe less players, less interest sometimes because it might be smaller populations, more niche populations we believe we can play to win.If you look at our pipeline, most of those fit. I would say [ACP-211] probably is on the bubble. Treatment-resistant depression is a fairly large space, but we argue its underserved, and we believe we have the opportunity to really make a difference there with something that has less monitoring.Forecasting Acadia's pipeline potentialDrugStageIndicationPeak sales potentialACP-101Ph. 3Prader-Willi Syndrome~$1-2BACP-204Ph. 2Alzheimers psychosis, Lewy body dementia psychosis>$2BACP-211Ph. 2Major depressive disorder>$2BACP-271Ph. 1-readyHuntingtons disease, tardive dyskinesia~$1-2BACP-711Ph. 2Essential tremor>$2BSOURCE: Table and estimates from research by Mizuho Securities analyst Uy Ear.How do you strike a balance between drugs seen as higher risk-reward, and those with maybe a more straightforward shot at getting through testing and onto the market?OWEN ADAMS: The balance for us comes with the ability to drive precision medicine into neurological diseases. The risks inherent within neuropsych, particularly, are subjective endpoints, large studies, high placebo effects. We all know it's hard. What we're trying to build is a movement into that space that's anchored in a bit more than just symptomatic endpoints.If you look at how we're running the Alzheimer's disease psychosis trial and the Lewy body dementia psychosis trial, what we unveiled at our R&D Day was an additional level of rigor around using biomarkers within those patients to try and understand the science.In each of those trials, while we have the more subjective endpoints of the various scales, we are also looking at augmenting that and making the populations more homogeneous using additional biomarkers.How important is having promising biomarkers when deciding whether or not to pursue a disease or subset of research? Are biomarkers part of go, no-go decisions?OWEN ADAMS: In some areas it's go, no-go. In the areas that we're in, the biomarker science is not necessarily concrete yet.My belief, having spent 25, 30 years in pharma and more recently, in oncology, where biomarker [reliance] goes without saying, is that as a society we need to get more precise about where we use medicines, what patients we use them, how we use them. Biomarkers are our current way of doing that, and we need to advance that within neuropsych. It's been sort of a backwater, in terms of advancing the science as fast as other areas. It's harder.My vision for Acadia becoming a biotech powerhouse in this space is built on precision medicine and data innovation. I'm really looking to push the company to advance the science, as well as, obviously, build a clinical trial we believe is the right one.If we look globally at countries where we want to have our medicines available, I think having biomarker-led patient population identification is going to help, particularly in single-payer systems. We have seen an unwillingness to pay [when] you just use a medicine on everybody and see what happens.Analysts claim that, during turbulent markets, companies will double down in areas they feel most experienced. You have two products: Nuplazid for Parkinsons disease psychosis and Daybue for Rett syndrome. How much have those two products influenced your pipeline decisions?OWEN ADAMS: I think [they do], but it's not necessarily based on the last six months of market volatility.With most pharma companies, you see a tendency to understand an area, have a lot of learning and then build the next product to be better. You can see many examples. In the case of Rett syndrome, Daybue has GI side effects, and we are looking to improve upon that. We look at 2591 with the hope that maybe we can evolve the side effect profile and still have the same efficacy.Similarly, Nuplazid is a great drug. But there are areas where it could do better. We were limited because it had a QT signal, so we've designed ACP- 204 to eliminate the QT signal and to act faster. Those things, for me, make sense, because you're really derisking, even though the analysts haven't given us much credit.If you look at essential tremor with ACP-711, which we just licensed in from Saniona in December, its a very different space; high unmet need, a bit of a graveyard. We think we found some really interesting science.211 is in major depressive disorder, another very different space. But I was at Janssen when we launched Spravato, so I know the space and understand what it takes.I don't want us to be so focused that we miss opportunities. It's about balancing where we know and then new areas where we think we can learn.What were the biggest lessons you learned from the Spravato story?Spravato became a blockbuster product over seven years. It was not a blockbuster product out the door. The efficacy was always really strong, but the infrastructure that the U.S. healthcare system had in place when we launched Spravato was very underdeveloped.Catherine Owen AdamsPermission granted by Acadia PharmaceuticalsJ&J had to spend a lot of time developing that infrastructure and support systems to allow doctors to be able to use it for the right patients. Every six months to a year, we'd learn more, and they'd put different things in place to ensure it continued to evolve. It was a huge investment to get Spravato to where it is now.We are now the beneficiaries of a much more defined system where doctors get paid for monitoring. When we launched Spravato, there wasn't even a code that doctors could use to get paid. There's always a downside to being the first, but it was a long, long road. Longer than they thought anyway.What are Acadias BD priorities right now?OWEN ADAMS: We've defined our focus: underserved neurological and rare diseases. That's where we want to play to win. Within that space, we're fairly open about the science we want. Science that is hopefully first in class or best in class. Everybody says that, but I mean it. I don't want to be the second, third or fourth to market, unless we've got something we believe is truly differentiating, which I think is where 211 fits.Acadia is not afraid to make scientific risk decisions, regulatory risk decisions. Where I won't make a risk decision is financially. We are in a very strong financial position, and I believe for the future of our company, we need to hold true to minimizing financial risk.With that in mind, I'd also like to look at some slightly later-stage products. We've got a lot of earlier-stage products. I would love to see us focusing a bit more on Phase 2 Phase 3 if it's possible but Phase 2-stage products, where we can get something to market in the 2030 timeframe.The upside of this market being a little bit difficult is that there are quite a few earlier-stage companies who maybe are more financially fragile than they were six months ago. So there's opportunity to go in and make a deal.You gave two big sales predictions during the R&D day. One was on Nuplazid and Daybue. Why did you release that figure?OWEN ADAMS: I've come up through the commercial line, and I believe analysts need to understand where I think we can get to. I'm strongly commercial, and I don't put numbers out there that I don't believe we can achieve. Those numbers are based on strong, objective data that I stand behind, and I think the analyst community are underestimating and have been overly cautious about both Daybue and Nuplazid.One of the big things in the last two months is that we got clarity on our patent for Nuplazid, now out to 2038, so that gives us a lot more runway. Nuplazid will, at some point if the Inflation Reduction Act exists as it does today, which is a big caveat run into a pricing situation with the IRA, as every other drug will. But Daybue has the potential to continue to grow and to go global. I think people are underestimating ... our ability to stabilize the current patient population.I'd rather have a conversation about: are we going to hit $1.5 billion to $2 billion or not, than say Im not willing to go there. As a CEO with a commercial background, I should be willing to go there. I can't hide behind, Well, I don't feel comfortable. Okay, then, why am I here?There was also that $12 billion peak annual sales forecast you put on the pipeline programs. Whats the biggest challenge you see getting to that number?OWEN ADAMS: Without wanting to be flippant, the biggest hurdle is the clinical outcome of the trials. The trial designs that we're looking at; the thinking that's gone into them; the additional biomarkers; the additional steps we're putting in place ... I think we're really focused on getting the best Phase 3 trial designs we can.Then, it becomes: can you commercialize with that outcome? Again, I stand behind the numbers. I don't think they're unreasonable. I've not pushed the team. I understand how all parts of a forecast are built.The biggest headwind, ultimately, will be the clinical data and the access environment that exists when we launch. Those two are outside of our control. We can design the clinical trials, we can prepare for the access environment, but that will make a difference. '