A recipe for managing data disclosure successfully with academic partners: A public gene therapy company perspective
When AVROBIO went public in June 2018, I found myself on the steep end of an unexpected but interesting learning curve regarding data disclosure. I had spent years leading Shire’s business development team, so I was well-versed in the regulatory requirements for public companies. However, I suddenly had to reckon with the complexities that ensued when AVROBIO transitioned from a small private company to a small public company. We were receiving data with (nearly) every blood draw and had to determine if the data were potentially material and, if so, when to disclose it. One of our toughest challenges in that transition turned out to be balancing our need to carefully analyze and disclose new data with our academic partners’ desire to publish first, and at a time of their choosing. This tension, at times, put a strain on our partnerships with academia, but we worked out a way to make the relationship work for both sides.
I often tell new recruits that AVROBIO has a “hunter-gatherer” mindset: We scour the globe for the best technologies and most exciting research programs with the intent of bringing them in-house through licenses and collaborations. Our assets are drawn from academia – saving us up to 10 to 15 years of research – and our first clinical studies were investigator-sponsored. In other words, AVROBIO is built on an academic scaffolding.
We believe this approach has served us well. Currently, we’re working with academic partners on two clinical trials of investigational lentiviral gene therapies designed to halt or reverse rare lysosomal disorders with a single dose and we’re sponsoring two other trials ourselves. But getting here has had its challenges.
New academic partners understandably are rarely familiar with the rules governing crucial issues for public companies, such as data disclosure. And while everyone shares the same end goal – to get safe and effective therapies to patients – potential miscommunications or uncoordinated disclosures of data can complicate matters.
In navigating these moments, I’ve taken away the following learnings:
1. Get specific about data disclosure
For a company seeking to develop one-time gene therapies, data disclosure can be a complex and nuanced issue.
Our clinical trials are small and we (or our collaborators) are measuring key biomarkers and clinical endpoints for each patient frequently. That means, in essence, that our clinical data come in continually, and in the early days, each new nugget had the potential to be material. This was all new to me: I came from a world where we got one big readout at the end of a trial and the results (in the case of early-stage trials) were typically not material to a large company like Shire with many clinical trials and commercial products.
By contrast, at AVROBIO, we knew from the start that we would need our collaborators to share their data in essentially real time. We had to negotiate upfront the question of what data we would receive and when.
Over time, we’ve found that it’s vital to spell out specific deadlines and the intervals for data to be communicated – not use vague language that’s up for interpretation. For example, we typically receive key data (e.g., enzyme activity, substrate levels, VCN) within days of it becoming available to our collaborator. We typically receive other non-key data every 30 days. This cadence has worked well for both sides. Safety incidents are reported on a separate, ongoing and expedited timeline as required by the U.S. Food and Drug Administration.
Along with our corporate counsel, we have to evaluate which data are potentially material and plan – while we are still at the negotiating table – for how those data updates may be shared and potentially disclosed.
In licensing contracts, there’s always a paragraph that deals with press releases and other public disclosures. Each party agrees to live by these rules, but there are exceptions to the rules that allow either party to disclose data when there is a legal requirement. Those of us who have been doing this for a long time are used to operating on a daily basis within the agreed-to rules. The crazy thing is, as a small, public gene therapy company, we found ourselves operating on a daily basis within the exceptions – an unusual predicament for most companies – but every early-stage biopharmaceutical company is likely to find itself in this same situation.
Additionally, the concept of not being able to disclose research at their own discretion can be a strange one for academic collaborators. After all, they’ve managed data disclosure professionally their whole careers and may not want data results – which could represent more than a decade of work – disclosed on someone else’s timetable.
Once we have a chance to explain our SEC-governed world and talk through the advantages of close cooperation and synchronization, we are eventually able to build mutual understanding and trust with our collaborators. Having a solid relationship, backed by clear contracts, has been the key to moving forward.
Beyond establishing when data are to be shared with us, we’ve found it beneficial to both sides to discuss reporting obligations ahead of time, and take the contract language one step further by including the concept that the parties will establish a communications and data release strategy. The typical academic publication language is still in the contract, but key publications typically don’t come until the end of the trial so they are less complicated to manage.
2. Add value – don’t just take it
We highly value our academic partnerships and hope to impart value back to our partners as well. And I don’t just mean payments. As a public company, we have far wider resources than an academic lab, including experienced R&D teams and communications strategists. These resources can benefit both parties, a point we have used successfully to help transform relationships into true partnerships.
Case in point: One collaborator wanted to publish data but we needed time to perform further analysis and gather more information so we could understand and assess the data fully. We presented them with two scenarios. They could publish as planned and likely receive modest recognition within their circle of colleagues. Or they could wait for our timetable, when we would amplify the news with the full weight of the AVROBIO’s corporate channels, involving a press release, social media and outreach to our network of media contacts, patient advocacy groups, scientific advisors and investors. It would almost certainly generate more awareness of them personally and their findings.
With the full weight of AVROBIO’s resources behind the communications, the decision to coordinate with AVROBIO became an easy one for the collaborator to make.
Beyond communications, our goal is to work closely with our academic collaborators where appropriate to navigate regulatory filings, optimize manufacturing, design clinical protocols and more – whatever it takes to potentially advance promising programs down the path to commercialization and delivery to patients and families.
After the all-consuming experience of managing a clinical trial – even a Phase 1 trial – our collaborators have been open to sharing their astonishment at the scale and complexity of the supporting work required. They are deep subject matter experts with a huge passion for the research they have spent decades nurturing. So, an initial wariness of industry is understandable, but we have now happily forged relationships that harness the unique strengths of both sides and give our investigational gene therapies the best chance of long-term success.
3. Don’t forget the ecosystem
In contract negotiations, it’s natural to start out with a laser focus on the researcher who’s spent his or her life developing the amazing science you’re hoping to license. But as I have learned at AVROBIO, academics don’t work in a vacuum.
You have to build a strong relationship with the researcher, of course. It’s equally important, though, to identify and reach out to all relevant parties in their academic ecosystem. The university tech transfer office is likely to be involved from the start. The communications department may want to weigh in as you negotiate disclosure provisions in the agreement. In some cases, the academic may have spun out his or her own startup, with its own investors, to advance the technology. In most cases the inventor of the therapy is a Ph.D., but the principal investigator (PI) of the trial is often an M.D. at their university, who may not technically be covered by disclosure agreements. It is crucial to build a relationship with the PI, explain data handling and disclosure obligations, and be sure they understand the benefits of a close relationship.
This broader ecosystem can create complications down the road around issues ranging from data disclosure to media outreach to engagement with the patient community. Once we had a physician in one of our investigator-sponsored trials who wanted to submit early patient data in an abstract without the inventor even knowing. Once we found out, we had to act quickly to address the issue, and called a meeting with the program inventor, lead physician and lead transplant surgeon to explain how abstract disclosure also might trigger SEC disclosure responsibilities. We discussed how we could work together on a coordinated disclosure strategy and schedule, and how that would benefit both parties. They understood the issues and implications and we’ve worked well together ever since. We now conduct a quarterly call where we discuss each side’s conference strategy and work together to ensure alignment and maximize exposure for the news.
Since our founding as a private company and through our transition to a public company, we’ve learned a great deal to help optimize our working relationships with our academic collaborators. In particular, we’ve learned to anticipate and navigate the different philosophies of academia and industry when it comes to handling clinical data and making public disclosures.
The number one lesson we’ve learned: While academic partnering is complex, it can also be among the most fruitful of an early-stage biopharmaceutical company’s relationships. Collaborations between industry and academia can enable the best science from research labs around the world to reach patients as safely and swiftly as possible. And that’s an endpoint worth celebrating.
This blog was co-written by Deanna Petersen, Chief Business Officer of AVROBIO, as part of the From The Trenches feature of LifeSciVC. Follow her on Twitter @dmp9818
For additional information related to AVROBIO and its programs and collaborations, please refer to AVROBIO’s filings with the Securities and Exchange Commission, including the section entitled “Risk Factors” in AVROBIO’s most recent Annual or Quarterly Report.