ElevateBio Announces AlloVir As First Spoke In Its Cell And Gene Therapy Hub
Executive Summary
ElevateBio revealed the first company to hitch up with its newly established centralized cell and gene therapy development, manufacturing and commercial capabilities – AlloVir, formerly ViraCyte, which is developing T-cell therapies to treat viruses in immunocompromised patients.
ElevateBio LLC Chairman and CEO David Hallal said when the company unveiled its hub-and-spoke model for cell and gene therapy development, manufacturing and commercialization that it would reveal the first spokes in its hub in the coming weeks and months. Nine days later, on 22 May, ElevateBio announced its affiliation with AlloVir, as well as a $120m series B venture capital round for the virus-specific T-cell therapy developer formerly known as ViraCyte LLC.
Linking up with AlloVir, founded in 2013 by researchers at Baylor College of Medicine's Center for Cell and Gene Therapy in Texas, aligns with what Hallal previously described as a benefit for small companies that are spun out of academia. By becoming ElevateBio subsidiaries, he said, the companies' scientific founders can focus on their research programs while relying on ElevateBio's centralized facilities and experts – including former executives from Alexion Pharmaceuticals Inc., like Hallal, and bluebird bio Inc. – to advance their cell and gene therapy candidates.
AlloVir co-founder and chief scientific officer Ann Leen, a professor of pediatrics at Baylor, told Scrip that was part of the appeal of engaging in a partnership with ElevateBio. Now, with $120m in venture capital and a partner to focus on late-stage clinical development of lead product candidate Viralym-M, Leen and her colleagues at Baylor and AlloVir will be able to focus on developing additional T-cell therapies.
"What we really wanted to do was partner now with an entity that has the wherewithal to be able to develop this product and move it through Phase III and subsequently, hopefully, to commercialization," she said.
AlloVir considered partnering with a large pharmaceutical company or another biotechnology firm, but its co-founders were familiar with some of ElevateBio's employees based on their prior work in the cell therapy field. In addition to the collective expertise ElevateBio has and the development, manufacturing and commercialization infrastructure that it is building, Leen said she appreciated the venture's entrepreneurial spirit and flexible mindset that isn't so apparent at a big pharma company.
"In general, with large pharma there's a little bit more bureaucracy involved – they're not as nimble, they're not as quick," she said. "With AlloVir being a small group and with Elevate growing, but very nimble, I think we can get a lot of work done in a short period of time."
Viralym-M Moving Into Multiple Phase III Studies
Hallal, who is serving as AlloVir's CEO, told Scrip that "the clinical development, quality manufacturing and eventually commercialization expertise really complement quite nicely what the team at Baylor has done to bring this super innovation platform through a positive proof-of-concept Phase II study and really on the doorstep for multiple registration trials."
Viralym-M is an off-the-shelf T-cell therapy manufactured using donor T-cells to restore natural immunity to up to six viruses that commonly develop in immune-compromised patients, particularly people who have undergone an allogeneic stem cell transplant or solid organ transplant.
In a Phase II proof-of-concept study, 93% of ASCT patients, who previously failed treatment with conventional antiviral therapies, responded to Viralym-M. The responses included complete responses and partial clinical responses, but most of the responders had complete elimination of detectable virus in their blood and resolution of major clinical symptoms.
ElevateBio, based on these data published in the Journal of Clinical Oncology in 2017, will move Viralym-M into multiple Phase III pivotal trials and additional proof-of-concept studies for various virus-associated diseases.
"We're anticipating that hemorrhagic cystitis – often associated with BK virus, but also can be associated with [cytomegalovirus (CMV)] or adenovirus – is likely to be our first pivotal study," Hallal said. "It's a high percentage of patients that receive an allogeneic stem cell transplant that suffer from hemorrhagic cystitis. And what we've learned from the transplant community is that, given the fact that all conventional therapies are highly ineffective and patients are really devastated by the condition, we're going to move forward with that as our initial pivotal study."
Three additional pivotal studies may test Viralym-M in adenovirus, antiviral-resistant CMV and Epstein-Barr virus (EBV)-associated malignancies or lymphoproliferative diseases. Proof-of-concept (POC) studies in the solid organ transplant setting also are anticipated.
Those studies, as well as the first clinical trials for AlloVir's preclinical product candidate ALVR106, a T-cell therapy targeting four community-acquired respiratory diseases (respiratory syncytial virus, influenza, parainfluenza virus and human metapneumovirus), are expected to begin within the next 12 months.
Funding, Partnering Opportunities As Programs Advance
Hallal said AlloVir's $120m series B financing should fund its clinical development programs for the next few years. Beyond that, he said, "we'll evaluate our capital needs and be thoughtful about using the [series B] proceeds and raising additional capital, up to and including an IPO, given the late-stage nature of the platform, in a very opportunistic way."
The recent financing was led by Fidelity Management and Research Co. with participation from Gilead Sciences Inc., F2 Ventures, Redmile Group, Invus, EcoR1 Capital, Samsara BioCapital and Leerink Partners Co-Investment Fund LLC.
In terms of seeking partners going forward for AlloVir's T-cell therapies, Hallal said ElevateBio feels confident it has the expertise to take Viralym-M – as well as additional assets from AlloVir and other ElevateBio subsidiaries – all the way from development through commercialization on its own.
"We see allogeneic stem cell transplants growing on an annual basis and being a sizeable patient population, and then when you add on to this solid organ transplants, namely renal transplants, we see this as an extremely large, underserved opportunity for us to serve patients," he said. "In aggregate, across a 50-country platform [in which] we have a lot of experience commercializing therapies worldwide, we see it as a very significant opportunity."
Differentiated Product In A Growing Cell Therapy Field
Leen noted that AlloVir is addressing that opportunity with a product that is differentiated from other T-cell therapies, including chimeric antigen receptor T-cell (CAR-T) therapies.
For instance, it's an allogeneic product manufactured from donor cells, which means that Viralym-M is an off-the-shelf therapy available for use when needed as opposed to autologous CAR-T therapies made from a patient's own cells and administered back to the patient weeks after the decision to treat. It also means that cells from a single person can be used to treat thousands of patients.
In addition, Viralym-M is not a genetically-modified product, Leen explained. AlloVir uses natural immune stimulant proteins (cytokines) combined with non-harmful fragments of viruses to activate and expand T-cells that work against the targeted viruses.
"We're growing these cells ex vivo; we add all of the ingredients together to our culture on day zero and then the device that we grow ourselves is left untouched for approximately two weeks while the T-cells specific to the viruses that we're targeting expand appropriately through the culture process," she said. "And then after two weeks we just harvest the product and then cryopreserve, or freeze, the cells down in multiple aliquots that are essentially then ready for administration to patients off the shelf."
"To me, it looks more like a conventional drug than any other cell therapy," Leen said.