Working (Well) With Patient Advocates: The Sponsor POV
A conversation with Aeovian Pharmaceuticals CEO Allison Hulme, Ph.D.
The partnership trifecta in clinical research is as follows: sponsor, CRO, and site. Ask nearly any stakeholder from one of the three, and they’ll mention the other two as key contributors to drug development. But, is there room for another?
Patient advocacy groups (PAGs) have been beating and continue to beat the drum about the importance of their involvement in drug development.
Notably, the collaboration between Aeovian Pharmaceuticals and the TSC Alliance reflects a true partnership. Together, they have screened and evaluated a drug candidate, positioning it for a Phase 2 proof-of-concept trial.
The partnership extended to the TSC Alliance’s participation in Aeovian’s $55 million Series B financing, supporting the continued clinical advancement of AV078, a first-in-class selective mTORC1 inhibitor for TSC-related refractory epilepsy.
In this Q&A, Aeovian CEO Allison Hulme reflects on their partnership with TSC Alliance and how it’s developed for the good of patients over the years.
(For TSC Alliance’s perspective, see the complementary interview with President and CEO Kari Rosbeck.)
Clinical Leader: How did Aeovian’s collaboration with TSC Alliance begin, and what made it evolve beyond a typical advocacy–industry relationship?
Allison Hulme, Ph.D.: I've been with the company for nearly six years now. Shortly after I joined, we engaged with the TSC Preclinical Consortium, which had collaborated with Professor Michael Wong at Washington University to develop a mouse model of TSC-related refractory epilepsy. Using this model, we evaluated several of our early-stage mTORC inhibitors designed to selectively inhibit the mTORC1 complex without off-target inhibition of mTORC2. These studies demonstrated that selective mTORC1 inhibition was as effective as non-selective mTORC inhibition targeting both mTORC1 and mTORC2. This finding was particularly important, as it reinforced our core hypothesis that TSC is fundamentally a disease driven by hyperactive mTORC1 signaling.
And from that came our lead development candidate, AV078, which has successfully completed a Phase 1 clinical trial. Without the data from the mouse model, it would've been very difficult for us to convince investors to support the continued clinical development.
The TSC Alliance has also introduced us to a number of clinical sites, the TSC Centers of Excellence, and patient advocacy groups in other geographies. So, when we design our Phase 2 proof of concept trial, we know that we're designing something that is practical and manageable for the patient population that we're aiming to treat.
With the data coming out of the animal models and the patient input, how did those two things impact the way that you designed your trial, whether it be visits, endpoints, or something else?
From an endpoint perspective, the objective is clear: accurately measure seizure frequency and demonstrate a meaningful reduction in seizures.
As for the protocol, we've worked with the TSC Alliance, other patient advocacy groups, as well as the clinical sites to ensure that we have a protocol that is practical for patients and their caregivers. One request was that we would allow for home visits for certain aspects of the protocol to minimize the burden and stress of bringing children that may or may not have developmental complications, cognitive complications as a result of their refractory epilepsy, or autistic spectrum-type manifestations, which may make it difficult for parents to get their children to the clinic.
Narrowing down a bit, what are some of the top patient requests?
They don’t want to be overburdened by the number of clinic visits, and that's where home visits become very important. Another key consideration is allowing patients to remain under the care of the physicians they know and trust. Many TSC doctors have a long-standing relationship with their patients and caregivers; there's a certain vocation in this rare disease where they're really focused on not just the epilepsy but the overall care of the patient.
And it works in your favor for adherence as well. If you're offering these decentralized elements, it helps them stay in the trial for the duration and produce better data, too.
Yes, there appears to be a keen desire to participate in our Phase 2 trial. And we have the advantage mechanistically, because the non-selective mTORC inhibitor everolimus is approved, participants and caregivers understand that mTOR inhibitors can work, but not optimally, because of dose-limiting toxicities. So, anything that may have better tolerability and safety is something the TSC community is looking for. We also believe that this approach positions us to deliver better efficacy, which is a key objective of the trial.
The TSC Alliance has helped secure funding for your clinical trials. How does one enter a financial partnership with a patient advocacy group?
The TSC Alliance Endowment Fund, a supporting organization of the TSC Alliance, participated in our Series B financing. Prior to the investment, we engaged directly with the Endowment Fund’s board and presented our investment opportunity. The board is deeply committed to supporting efforts that accelerate the development of new treatments for the TSC patient community.
Heading into the Phase 2 proof of concept, what are the next milestones that you're looking for? Not just in your trials, but in the partnership?
It's early days. We've recently closed the Series B financing. The next milestone will be to fully enroll the Phase 2 trial. We look forward to continuing to work with the TSC Alliance and the TSC community to ensure that we achieve that important milestone and continue to raise the awareness of the high unmet need that exists for patients with TSC.
About The Expert:
Allison J. Hulme, Ph.D., is the president and CEO of Aeovian Pharmaceuticals. Dr. Hulme joined Aeovian in January 2020 as CEO, president, and board member, bringing with her 30 years of experience in drug development and commercialization. Prior to this, she was the COO, head of research and development, and board member at Sophiris BIO, establishing the company’s California operations and leading the Topsalysin program from IND to Phase 3 in BPH and prostate cancer. Prior to joining Sophiris, Dr. Hulme was the executive vice president and head of global development at Elan Corporation plc. Before Elan, Dr. Hulme held several positions in clinical research at Glaxo Wellcome Pharmaceuticals and was a lecturer in cell biology at Luton University. Dr. Hulme holds a first-class honors degree in cell biology from the University of Bedfordshire and a Ph.D. from Cranfield Institute of Technology.