Raven-built Aliada shuttles its potential best-in-class Alzheimer's treatment to AbbVie

October 28, 2024

Imagine if you could deliver any biologic or oligonucleotide therapy across the blood-brain barrier (BBB) and deep into the brain with a simple injection – no direct infusions into the spine or brain required. Even better, what if you could deliver an antibody into the brain with a low-volume, subcutaneous shot? 

These were the possibilities we imagined in 2020, when we first started discussing “Project Triple” with Johnson & Johnson Development Corporation (JJDC), J&J’s corporate venture arm. J&J had been developing the Modular Delivery (MODEL) platform, a novel blood-brain barrier (BBB) crossing technology that employed the transferrin (TfR) and CD98 receptors to deliver cargo directly into the brain. Various competing internal priorities within J&J meant it was likely going to be difficult for them to realize the full value of the platform. JJDC’s team also knew that RA Capital had been building out a full suite of Venture Partners, EIRs, and company-building capabilities (what is now Raven) that could move quickly to start a new company to maximize the full potential of the technology. Together, we formed Aliada Therapeutics in 2021.

Today, AbbVie announced it is acquiring Aliada for $1.4 billion, motivated by the potential for ALIA-1758, Aliada’s lead program, to be best-in-class for the treatment of Alzheimer’s disease, and by the potential of the BBB-crossing platform to enhance its discovery and development efforts for other difficult-to-treat neurological diseases. As we congratulate the Aliada team, we wanted to share a bit more of the story behind the second significant acquisition from our Raven incubator this year (read more about our first here) and the first full-circle acquisition of a company we built with technology spun out from a larger company (the basis for our Project Condor work).

Aliada was co-founded by RA Capital (Senior Managing Director Josh Resnick and Managing Director Laura Tadvalkar), Raven (Venture Partner & founding CEO Adam Rosenberg, Venture Partner & CMO Michael Ryan, and Entrepreneur-in-Residence & Senior Director of Corporate Development Danielle Feldman), JJDC (VP Venture Investments Marian Nakada), and J&J (Global Head of Janssen BioTherapeutics Sanjaya Singh, now founder & CSO at Third Arc Bio).  

Putting together a new neuroscience company required vision, operational excellence, and as always, a little bit of grit. Our Raven team assembled an operating plan that would allow us to transfer the substantial knowledge base from J&J into the company and to advance the platform efficiently towards the clinic. Our TechAtlas team started brainstorming “killer applications” for the technology – of all the antibody, enzyme, and oligonucleotide cargoes we might want to deliver, where should Aliada focus its resources in order to develop best-in-class therapies to meet unmet needs for patients? Negotiating the spinout of the platform technology was complex, and was deftly navigated over the course of several months by counsels on both sides.

As the company got up and running, Aliada chose an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody with an anti-TfR delivery module as its lead program: ALIA-1758 for the treatment of Alzheimer’s disease. At the time of company formation, the beta-amyloid reduction approach to Alzheimer’s was starting to show real therapeutic potential, yet our belief was that the field would be commercially limited unless and until a low-volume, high-efficacy, subcutaneously delivered product could be developed. 

Our view was that this wasn't simply a matter of convenience: the infrastructure simply does not exist to provide infusions to the millions of patients with moderate-to-severe dementia who could benefit from this type of treatment. Furthermore, there was the potential for the drugs to be used in mildly symptomatic patients, or pre-symptomatic patients with genetic risk factors – a population where the convenience of subcutaneous administration would be critical. We became convinced that a best-in-class therapeutic antibody that could achieve the level of potency and BBB delivery to be a subcutaneous product would be very valuable, and would be likely to garner substantial pharma interest.

To accelerate our progress and expand the platform, we brought in OrbiMed and Sanofi Ventures for a seed extension financing in late 2022, and then hired the company’s current leadership: Steve Sweeney as COO and John Dunlop as CSO. In mid 2023, Chiesi Global Rare Diseases announced an R&D collaboration with Aliada to partner on a number of lysosomal storage disorders – an area where Chiesi has significant experience and expertise from discovery through commercialization that would be expanded by tapping into Aliada’s MODEL platform. Partnering on promising indications meant Aliada could drive platform value while staying focused on its Alzheimer’s and other internal programs.

With a strong syndicate around the table, Aliada was excited and fully-prepared to advance ALIA-1758 on its own. But we also knew that at some point, the resources of a large pharma company might help accelerate and broaden the benefit that ALIA-1758 and other therapies could bring to patients. Getting drugs for Alzheimer’s and other neurological diseases to patients quickly and efficiently requires significant capital investments and very large trials that are a good match for the capital resources and operational scope of a global pharma.

It became clear in recent months that several large biopharma companies agreed with us about the potential of ALIA-1758 and the Aliada platform, and partnership interest picked up accordingly. When it did, Aliada was able to quickly bring on RA Capital Venture Partner Emily Minkow as Consulting Chief Business Officer (another advantage of being in the Raven family!) to work with the company to strategize and develop a process that would give ALIA-1758 the best chance of success while maximizing value to stakeholders; this ultimately turned into negotiating an acquisition, which, with the help of our friends at Centerview and Fenwick, Aliada was able to sign efficiently. 

We are particularly excited that Aliada advanced ALIA-1758 into a Phase 1 first-in-human single ascending dose trial earlier this year. For the first time, the company is testing whether Aliada’s MODEL platform enables the safety, tolerability, and pharmacokinetic parameters we expect to see based on the preclinical data they have generated to date. We’re hopeful that ALIA-1758 will emerge as a best-in-class amyloid-beta antibody and become an important medicine that makes a significant difference for Alzheimer’s patients and their families, and we are confident that ALIA-1758 and the pipeline are in good hands with AbbVie’s neuroscience team.

Congratulations to the Aliada and AbbVie teams; we at RA Capital will enjoy following ALIA-1758’s progress. A huge thanks to our partners at J&J, JJDC, OrbiMed, and Sanofi Ventures. We look forward to co-creating more Raven newcos that unlock the potential of promising therapies and technologies.