BioPharma, Pharma

Takeda Commits $100M for Chance to Bring Immunotherapy to Alzheimer’s Disease

Takeda Pharmaceutical has secured an option on an Alzheimer’s disease immunotherapy from AC Immune that is on track to report its first Phase 2 data later this quarter. Exercising the option would make Takeda responsible for Phase 3 testing of the therapy, putting AC Immune in line for up to $2.1 billion in milestone payments.

Alzheimer’s disease can be treated with antibody drugs that reduce levels of amyloid beta protein in the brain. Clinical-stage biotech company AC Immune is developing a novel therapy that sparks the immune system to clear away amyloid plaque, and Takeda Pharmaceutical sees enough promise in this approach to commit $100 million for the opportunity to pick up this experimental therapy.

The AC Immune drug, code-named ACI-24.060, is currently being evaluated in the Phase 2 portion of a Phase 1b/2 study. Under the deal terms announced Monday, Takeda’s upfront payment gives it an exclusive option to license global rights to this immunotherapy.

ACI-24.060 is an immunogenic peptide that is presented to the immune system’s B cells in a way that mimics the pathological form of amyloid beta. This presentation is intended to spark activity from antibodies that bind to pathological forms of the protein. In preclinical research, Lausanne, Switzerland-based AC Immune has reported that the drug led to higher blood levels of immunoglobulin G antibodies that were associated with reduction in amyloid plaque. In tests in monkeys, AC Immune reported a favorable safety profile for the drug.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

AC Immune is responsible for completing the placebo-controlled Phase 1b/2 study, which is evaluating for ACI-24.060 in patients with early Alzheimer’s. The study is also testing the immunotherapy as a treatment for patients with Down syndrome. Under the Takeda agreement, the Japanese pharmaceutical giant may exercise its option after it receives predefined clinical data on the first three Alzheimer’s patient cohorts from the ongoing study, AC Immune said in a regulatory filing. The first Phase 2 data on amyloid plaque reduction after six months of treatment will be reported in the current quarter, potentially paving the way for Phase 3 testing, AC Immune said Monday in its report of financial results for the first quarter of 2024.

“We believe the maximum impact of ACI-24.060 can best be realized by partnering with Takeda at this critical juncture in its development, which will help us move rapidly into Phase 3,” AC Immune CEO Andrea Pfeifer said in a prepared statement. “This agreement allows us to leverage the developmental expertise, strategic vision and financial capacity of an accomplished organization that has demonstrated its ability to execute the type of comprehensive global program required for Phase 3 trials in Alzheimer’s disease while allowing us to focus on completing Phase 1b/2 development and accelerating our efforts to replicate this success with enhanced funding for our early-stage pipeline.”

[Updated to add the following three paragraphs with analyst commentary.] An anti-amyloid beta, or “Abeta,” approach already has partial validation from the FDA approval of the amyloid plaque antibody -busting drug Leqembi, from Eisai, as well as donanemab, an Eli Lilly drug still under regulatory review, Leerink Partners analyst Marc Goodman wrote in a March research note. But safety could be a key differentiator for an Alzheimer’s immunotherapy. Antibody drugs developed for the disease introduce the risk of amyloid-relating imaging abnormalities (ARIA), brain bleeding and swelling that is a known adverse effect of this class of therapies. An earlier formulation of AC Immune’s therapy yielded mixed Phase 3 data. While the results showed favorable safety with no signs of ARIA, the immune response was “suboptimal,” Goodman said.

ACI-24.060 is a new formulation incorporating changes intended to boost the immune response. Goodman said translation of immune response to amyloid beta clearance and/or clinical benefit remains a key question. Also, active immunotherapy may take longer to show an effect compared with antibody drugs, he added. While those questions remain unanswered so far, the Takeda deal is positive news for AC Immune, Goodman wrote in a Monday research note.

“Once again management has executed on a significant partnership with a big pharma company to develop an asset that has received minimal value in the stock, confirming our long-term thesis that this management team can leverage its two proprietary drug discovery platforms and diversified pipeline to drive value,” Goodman said.

The agreement makes AC Immune eligible for up to $2.1 billion in milestone payments, which includes an option exercise fee in the low-to-mid-hundred millions of dollars, according to the regulatory filing . After exercising that option, Takeda will be responsible for clinical development of the Alzheimer’s drug. Takeda will also handle regulatory submissions as well as commercialization if the drug is approved. AC Immune will receive royalties from Takeda’s sales of the immunotherapy.

ACI-24.060 would give Takeda another opportunity to address Alzheimer’s, but with a drug candidate that has been de-risked with clinical data. The company previously partnered with Denali Therapeutics on the development of an antibody engineered to penetrate the brain to hit and activate a target called TREM2. Last August, the two companies announced they would discontinue clinical development of this Alzheimer’s drug after safety signals emerged in Phase 1 testing. Takeda also has a research collaboration with Cure Network Dolby Acceleration Partners focused on developing small molecules that target tau in Alzheimer’s and other brain disorders.

AC Immune has other alliances in Alzheimer’s. Its anti-tau immunotherapy ACI-35.030 is currently in mid-stage clinical development under a partnership with Johnson & Johnson subsidiary Janssen Pharmaceuticals. A tau aggregation inhibitor is in preclinical development under a partnership with Eli Lilly. Two AC Immune antibodies, semorinemab and crenezumab, were partnered with Roche’s Genentech division. But after disappointing clinical trial results, Genentech terminated the alliance early this year, returning to AC Immune rights to both antibodies.

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