AL-002

Alzheimer’s disease medicines commercialized in the past two years validated amyloid beta as a drug target, but these antibody therapies still have a hard time penetrating the membrane that covers blood vessels supplying the brain. AbbVie aims to best those drugs through its acquisition of Aliada Therapeutics, a clinical-stage biotech whose technology enables large molecules such as antibodies to cross this protective barrier. AbbVie announced Monday it is paying $1.4 billion in cash to acquire Aliada, a biotech that just entered the clinic earlier this year. Boston-based Aliada gets drugs across the blood-brain barrier (BBB) by leveraging receptors that transport substances into the brain. Lead Aliada program ALIA-1758 is an antibody engineered with binders for transferrin, which transports iron into the brain, and CD98, which transports certain amino acids. The drug comes from a platform technology called Modular Delivery, or MODEL. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health “We’re essentially taking advantage of normal physiological brain transport processes, and if you like, we’re hijacking those by attaching therapeutic cargos to our delivery modules to allow brain delivery,” Aliada Chief Scientific Officer John Dunlop explained in an interview during the BIO Conference in June. Aliada licensed MODEL from Johnson & Johnson subsidiary Janssen, which had used the technology to develop ALIA-1758. Aliada co-founder Danielle Feldman, who is senior director of corporate development for the company, was with RA Capital Management when her search for new technologies led her to Johnson & Johnson Innovation—JJDC, Dunlop said. Those discussions led both parties to conclude that the best way for the MODEL technology to realize its value was as a standalone company undistracted by the goings-on of a big pharmaceutical company. Aliada was formed at the end of 2021, with seed financing from RA Capital and J&J. OrbiMed and Sanofi Ventures later joined an extension of the financing. Dunlop declined to disclose how much was invested, but securities filings show the company raised $1 million in 2021, followed by nearly $32 million in late 2022. Dunlop did say Aliada had enough capital to support the lead program through Phase 1b proof-of-concept testing in Alzheimer’s. Clinical trial records show a Phase 1 trial began in May with a targeted enrollment of 52 healthy adults. According to Dunlop, ALIA-1758’s affinity for its target receptors means that more drug can get into the brain per dose, which should translate to needing a lower dosage level to achieve the desired therapeutic effect. A lower dose could reduce the adverse effects associated with amyloid-reducing drugs. Eisai’s Leqembi, which won full FDA approval last year, and Eli Lilly’s Kisunla, approved in July, carry warnings on their labels for risks of bleeding and swelling complications. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB AbbVie has been spreading its bets in Alzheimer’s drug R&D. The company earlier this year reportedly discontinued development of ABBV-916 as a monotherapy, but is still leaving the door open for applications of the antibody as part of combination treatments. An Alzheimer’s partnership with Alector began in 2017. Two years ago, AbbVie terminated one program that had reached Phase 1 testing, opting to focus the alliance’s efforts on a second Alector program, AL002. This drug is an antibody designed to modulate the TREM2 receptor as a way of enhancing the activity of microglia, immune cells found in the central nervous system (CNS). Alector is responsible for Phase 1 and 2 testing, after which AbbVie has the option to license the drug. AbbVie’s pipeline currently shows AL002 is still in Phase 2 testing. In 2022, AbbVie paid $130 million up front to acquire Syndesi Therapeutics, developer of small molecule drugs that modulate synaptic transmission. Syndesi’s most advanced program, renamed ABBV-552, targets synaptic vesicle protein 2A (SV2A). AbbVie’s pipeline currently shows this program is in Phase 2 testing. AbbVie said it expect to close the Aliada acquisition by the end of this year. In the company’s announcement of the deal, Roopal Thakkar, executive vice president, research and development and chief scientific officer, AbbVie, said neuroscience is one of the company’s key growth areas. “This acquisition immediately positions us to advance ALIA-1758, a potentially best-in-class disease-modifying therapy for Alzheimer’s disease,” he said. “In addition, Aliada’s novel BBB-crossing technology strengthens our R&D capabilities to accelerate the development of next-generation therapies for neurological disorders and other diseases where enhanced delivery of therapeutics into the CNS is beneficial.”

iStock/ Evgeny Gromov The acquisition of Aliada Therapeutics gives AbbVie access to a Phase I anti-amyloid antibody as well as the biotech’s novel platform engineered for efficient blood-brain barrier transport. With several early- to mid-stage assets already in its pipeline , AbbVie took an even deeper dive into the Alzheimer’s space Monday with the acquisition of Aliada Therapeutics. At the heart of the deal—which will see AbbVie pay $1.4 billion in cash to acquire the Boston-based biotech—is ALIA-1758, an anti-amyloid antibody currently in Phase I development for Alzheimer’s disease. This is the same drug class that recently burst onto the scene in the form of Biogen/Eisai’s Leqembi and Eli Lilly’s Kisunla , both approved in the last two years as the first disease-modifying therapies for Alzheimer’s. The acquisition also gives AbbVie access to Aliada’s Modular Delivery (MODEL) platform, which is “engineered for both efficient BBB (blood-brain barrier) transport and downstream therapeutic functionality,” according to the company’s website . In an investor note Monday, BMO Capital Markets analyst Evan David Seigerman said BMO views the deal “as positive for AbbVie shares, albeit risky given the indication and stage of development, expanding into a therapeutic area it knows well and continuing to bolster its pipeline for long term growth beyond recent commercial success with Skyrizi & Rinvoq.” Stifel analysts added in an investor note that the deal “seemingly offers a vote of confidence in amyloid, just as sentiment in the space is reaching an all-time low.” ALIA-1758 targets pyroglutamate amyloid beta, which is similar to the epitope targeted by Eli Lilly’s Kisunla , John Dunlop, chief scientific officer at Aliada, previously told BioSpace . The novel technology targets transferrin and CD98 receptors TfR and CD98, which are highly expressed in the brain’s endothelial cells, and uses the transferrin receptor to drive its cargo to cells and force degradation and elimination of the plaques, Dunlop explained. By transporting the cargo in this way, a higher concentration of the antibodies is delivered across the blood-brain barrier to drive therapeutic benefit. “Many promising CNS-targeted therapies fail to reach late-stage trials due to their inability to cross the blood-brain barrier,” Michael Ryan, chief medical officer at Aliada, said in a statement Monday, adding that the company is “excited about AbbVie’s commitment to bringing ALIA-1758 to patients with Alzheimer’s disease.” AbbVie already has a considerable presence in the Alzheimer’s R&D space, and Seigerman noted that Aliada’s assets are potentially complementary to a number of Alzheimer’s assets that AbbVie already has in development. The company’s pipeline includes ABBV-916, an anti-AβpE3 antibody; ABBV-552, an SV2A modulator being evaluated to target nerve terminals to enhance synaptic efficiency; and AL002, an antibody being developed in partnership with Alector Therapeutics. “Neuroscience is one of our key growth areas and we are committed to driving innovation in this field to address critical unmet needs for patients living with seriously debilitating neurological diseases such as Alzheimer’s disease,” Roopal Thakkar, EVP of research and development and chief scientific officer at AbbVie, said in a statement . Aliada’s platform “strengthens our R&D capabilities to accelerate the development of next-generation therapies for neurological disorders and other diseases where enhanced delivery of therapeutics into the CNS is beneficial.” The deal is expected to close in the fourth quarter of 2024, subject to regulatory approvals and other customary closing conditions.