DNL-919

Astellas' geographic atrophy approval, Singapore's 20 years of work on advancing biotech, and AstraZeneca and CanSino's mRNA deal made our news this week. Astellas has won FDA approval for a geographic atrophy therapy that the company obtained from its acquisition of Iveric Bio. A Fierce Biotech report examined Singapore's biotech landscape 20 years into a nationwide initiative to become a biotech hub. AstraZeneca signed an mRNA vaccine manufacturing deal with China's CanSino Biologics. And more. 1. Astellas wins FDA approval of eye disease drug Izervay and may have edge in market battle with Apellis Astellas’ $5.9 billion acquisition of Iveric Bio has borne fruit. The FDA has approved Iveric’s geographic atrophy therapy Izervay. The nod came less than six months after Apellis’ Syfovre became the first FDA-approved therapy for the eye disease. Syfovre’s first-to-market edge was recently diminished by reports of severe side effects. 2. 20 years in, Singapore still searches for its biotech success story In a new report, Fierce Biotech examined Singapore’s biotech ambition 20 years after a government-led push to become a biotech hub. Temasek-backed Tessa Therapeutics’ sudden dissolution inevitably weakened investors’ confidence in Singapore’s biotech industry, which also faces a talent shortage. But observers and stakeholders believe Singapore may still have a big biotech success story. 3. AstraZeneca pursues mRNA, signs vaccine manufacturing deal with China's CanSino AstraZeneca signed an mRNA manufacturing deal with China’s CanSino Biologics. The Chinese company will help make certain vaccines by AZ during R&D. The deal comes a year after AZ axed an mRNA strategic partnership with Moderna in cardiovascular and oncology. 4. Daiichi Sankyo tipped to dominate antibody-drug conjugate market through 2029 With AstraZeneca-partnered Enhertu leading the way, Daiichi Sankyo will be the top antibody-drug conjugate player through 2029, GlobalData predicted. Sales from Daiichi’s ADCs will reach $10 billion by then, while Seagen and Roche will follow as distant second and third, respectively. In a recent update, Daiichi itself expects its oncology revenue could reach over $6.3 billion by its 2025 fiscal year. 5. Poseida sells $50M stake to Astellas, extending cash runway as gene therapy programs reviewed SK Bioscience helps keep Novavax afloat, buying 7% stake in vaccine maker for $85M In two cases where an Asian biopharma company bought stakes in a U.S. firm, SK Bioscience injected $85 million into floundering vaccine maker Novavax for a 7% holding, and Astellas put up $50 million in exchange for an 8.8% stake in Poseida Therapeutics and the right of first negotiation for P-MUC1C-ALLO1, a CAR-T cell therapy under development for solid tumors. 7. Takeda, Denali drop Alzheimer's asset after phase 1 peak reveals 'narrow therapeutic window' Takeda and Denali Therapeutics have decided to stop developing their Alzheimer’s disease candidate TAK-920. Takeda signed up to co-develop the antibody transport vehicle back in 2021. But the drug soon hit an FDA clinical hold, and new phase 1 data suggested the drug was too toxic at a high dose. Takeda and Denali are now looking at back-up molecules. 8. Takeda shells out $42M to settle Medicaid fraud claims in Texas Takeda has agreed to pay $42 million in Texas to resolve a whistleblower case that accused the company’s Shire unit of paying clinical nurse educators to refer and recommend ADHD drug Vyvanse to doctors in 2014 and 2015. Takeda denied the claims but said the deal is “in patients’ best interest.” Other News of Note 9. Astellas plots new Cambridge facility for R&D, business development (Release) 10. BioNTech expands DualityBio pact to include 3rd ADC (Release) 11. Sunbird Bio snaps up Glympse Bio for protein-based diagnostics

The narrow therapeutic window was due to safety signals of moderate hematologic effects at the highest dose. Takeda and Denali Therapeutics have made the joint decision to end work on their Alzheimer’s disease therapy after a glimpse at early phase 1 data suggested they couldn't pursue the highest dose tested. The Japanese Big Pharma took up the offer at the tail end of 2021 to co-develop the asset, an antibody transport vehicle (ATV) called DNL919 or TAK-920, but the program was soon hit by a clinical hold from the FDA due to a preclinical toxicology assessment. While the drug eventually entered the clinic in July 2022, it seems that the early data have raised some alarm bells. “In the phase 1 study, DNL919 was clinically well tolerated at doses with demonstrated changes in CSF biomarkers and there were no serious adverse events or severe treatment emergent adverse events,” Denali explained in its second-quarter earnings report. “However, safety signals of moderate, reversible hematologic effects were observed at the highest dose tested, suggesting a narrow therapeutic window for the Alzheimer’s disease patient population,” the biotech added. It’s not the end of Takeda and Denali’s partnership, which was established back in 2018 to look at three targets for “neurodegenerative disorders, including Alzheimer’s disease and other indications.” With DNL919 cast aside, the two companies will “focus research efforts on back-up molecules in preclinical development, including exploration of potential combination therapy given recent new drug approvals in Alzheimer's disease.” Judging by the biotech’s comments elsewhere in the release, this consideration of potential combo therapies also played a part in the decision to scrap DNL919, with Denali saying that along with the “totality of clinical data emerging” from the phase 1 trial, it had also considered “the rapidly evolving treatment landscape for Alzheimer's disease whereby an understanding of drug combinations with newly approved therapies will be important.” It could be that the two companies hope to have more luck hooking their wagons onto Biogen and Eisai's already approved Leqembi or Eli Lilly’s close contender donanemab. Unlike those amyloid-targeting antibody therapies, the aim of DNL919 is to activate TREM2 in the hopes of improving microglial function, which the biotech has previously described as the "resident immune cells of the brain." Function loss in the TREM2 receptor is associated with increased risk for Alzheimer's, according to the biotech. That appears to have been backed up in the same batch of early phase 1 data, which Denali said had indicated “robust target engagement and effects on microglial biomarkers, which were consistent with preclinical studies that demonstrate that ATV:TREM2 induces robust changes to a responsive microglial cell state.” Biogen has its own Alzheimer’s collaboration with Denali, having exercised its option in April to license the biotech’s ATV-amyloid-beta program. The two companies are also investigating a LRRK2 inhibitor called BIIB122 in Parkinson’s disease.