RaQualia Pharma, Inc.

The FDA approval for Daiichi Sankyo's Vanflyta, a protein degrader deal between Astellas and PeptiDream, and a Takeda trial flop made our news this week. Daiichi Sankyo's FLT3 inhibitor overcame FDA rejection to win an approval. Astellas signed another protein degrader deal, this time with PeptiDream. Takeda's enzyme replacement therapy flunked a mid-stage trial in a rare neurological disorder. And more. 1. After FDA snub, Daiichi's Vanflyta gains US approval and tees up AML clash with Novartis, Astellas About four years after an initial FDA rejection, Daiichi Sankyo has finally won approval for its FLT3 inhibitor quizatinib as a treatment for acute myeloid leukemia. Now marketed as Vanflyta, the Daiichi drug will compete against Astellas’ Xospata and Novartis’ Rydapt. Vanflyta’s label only covers cancers with FLT3-ITD mutations, while its rivals' approvals cover any FLT3 mutations. 2. Astellas notches another protein degrader pact with $21M upfront for PeptiDream Astellas has put down 3 billion yen ($21 million) up front to tap PeptiDream’s peptide discovery platform to develop protein degraders. PeptiDream will also be in line for potential milestone payments up to 20.6 billion yen ($145 million) per target, plus single-digit percentage sales royalties. Astellas has previously inked protein degrader deals with Cullgen and Fimecs. 3. Takeda suffers setback as promising neuroscience prospect flunks phase 2 Takeda’s TAK-611, an enzyme replacement therapy proposed for the rare genetic disease metachromatic leukodystrophy, has failed in a mid-stage trial. The phase 2 trial didn’t meet primary or secondary endpoints, according to Takeda. The readout was listed as a potential inflection point for Takeda’s late-stage neuroscience programs for this fiscal year. 4. Takeda hypes up dengue vaccine launch progress as Vyvanse generics loom Takeda is touting the progress of its dengue vaccine Qdenga despite a recent decision to pull its application in the U.S. The company is now focused on some endemic markets, which make up about 80% to 85% of the vaccine’s peak sales projection of $1.6 billion to $2 billion, CEO Christophe Weber said on a confererence call. Takeda is getting closer to having end-to-end in-house production capability for Qdenga by 2025, he said. 5. Lawmakers propose federal database to track supply chain vulnerabilities Sen. Gary Peters (D-MI), chair of the Homeland Security and Governmental Affairs Committee, has teamed with Republican Sens. James Lankford (R-OK) and Mike Braun (R-IN) to introduce a bill to create a federal database to track supply chain vulnerabilities. The Mapping America’s Pharmaceutical Supply Act would catalog the origin of each drug, quantities available and the location of their manufacturing facilities. 6. Centaur Pharmaceuticals slapped with FDA warning letter outlining quality, cleaning lapses Centaur Pharmaceuticals’ drug ingredient plant in Maharashtra, India, got an FDA warning letter with two observations about quality deficiencies and lapses in cleaning protocols. The agency is demanding Centaur completely assess its documentation systems and manufacturing standards training program. Other News of Note 7. AstraZeneca enlists SK Chemicals to produce diabetes combo drug Sidapvia 8. India’s pharma exports continue to rise despite manufacturing scandals, trade body says (Reuters)

Astellas Pharma is far from alone in viewing cancer as a major growth area, but the Japanese drugmaker has specifically identified a type of therapy called targeted protein degradation as one of the key areas for increasing revenue. It just struck its second deal in the past two months to help it execute on that strategy and perhaps stand apart from others pursuing the same type of drugs. Under a partnership announced Tuesday, Astellas will work with PeptiDream to discover new protein degraders using the technology of that company. Specific targets were not disclosed, but they will be selected by Astellas. The deal also grants Tokyo-based Astellas the option to select up to three additional targets for inclusion in the collaboration. Astellas will pay PeptiDream 3 billion yen (about $21 million) up front. PeptiDream, based in Kawasaki, Japan, is eligible to receive up to 20.6 billion yen (about $145.8 million) in milestone payments for each target. Targeted protein degradation leverages a cell’s built-in system of disposing of old or damaged proteins as a way to get rid of cancer-causing proteins. Those proteins are directed to this system with a small molecule that recruits a molecular tag that marks a protein for disposal. Targeted protein degradation is a hot field. Kymera Therapeutics and Arvinas are among the biotech companies developing small molecules for targeted protein degradation, both of them in partnership with large pharmaceutical companies. PeptiDream’s peptide discovery platform technology identifies macrocyclic peptide candidates. Macrocyclic peptides are larger than small molecules, giving them some features that are characteristic of large molecules. But unlike large molecules, macrocyclic peptides can be made into an oral drug. Also important, it’s hoped that macrocyclic peptides can address targets that are tough to hit with small molecules. “Targeted Protein Degradation is one of the Primary Focuses of Astellas,” Chief Strategy Officer Adam Pearson said in a prepared statement. “We hope this collaboration will bring synergies between the two companies’ cutting-edge research and will ultimately lead to the expansion of Astellas’ portfolio and development of new therapeutics for patients with significant unmet medical needs.” Astellas is not abandoning the use of small molecules for targeted protein degradation. Last month, Astellas began a collaboration that will use Cullgen’s technology, which finds ways to target proteins thought to be undruggable. The San Diego-based company received $35 million up front. Astellas could pay Cullgen another $85 million if it licenses the lead program from the collaboration. Cullgen could receive up to $1.9 billion in milestone payments, plus royalties from sales of a commercialized product. The Cullgen deal followed a 2022 alliance with Fimecs focused on discovering small molecule protein degraders against multiple unnamed targets. Financial terms were not disclosed. Astellas has reached Phase 1 testing with ASP3082, an internally developed drug candidate designed to degrade a cancer target called KRAS G12D. Mutated versions of this protein are found in pancreatic cancer and colorectal cancer among other cancer types. Astellas’s top-selling product is the cancer drug Xtandi, which is facing patent expirations. In 2021, the company outlined a strategic plan for growing the pipeline and revenue over the next five years. Executives said this strategy will focus R&D on five main areas: genetic regulation, immuno-oncology, blindness and regeneration, mitochondria, and targeted protein degradation. Astellas bolstered the vision part of its corporate strategy in May, announcing the $1.3 billion acquisition of Iveric Bio, whose lead program is a potential treatment for geographic atrophy. An FDA decision for that drug is expected in August.

PeptiDream will be in line for potential discovery, development and sales-based milestones reaching 20.6 billion yen ($145 million) per target. Is there anything Astellas likes more than a protein degrader pact? The Japanese pharma has followed up agreements with the likes of Cullgen and Generian Pharmaceuticals by tapping PeptiDream for its latest partnership. The agreement will see the two companies use PeptiDream's peptide discovery platform to find “multiple next-generation protein degraders targeting diverse targets that go beyond existing technologies,” according to a July 25 release. The initial focus will be on two targets selected by Astellas, with the pharma having the option to expand to an additional three targets at a later date. Astellas will be responsible for the development and commercialization of any products that result from the collaboration, for which the Tokyo-based pharma is paying 3 billion yen ($21 million) upfront. PeptiDream will also be in line for potential discovery, development and sales-based milestones reaching 20.6 billion yen ($145 million) per target, along with single-digit percent royalties. Protein degradation has emerged as a hot modality in recent years as evidence of its potential to address undruggable proteins has been uncovered. The PeptiDream collaboration comes a month after Astellas paid Cullgen $35 million upfront to make use of the U.S.-based biotech’s platform. But Astellas’ interest in the technology goes further back. Having identified the approach as one of its five primary areas of focus, the pharma teamed up (PDF) with Fimecs, a biotech built on Takeda technology, and allied with Generian to work on small molecules that activate, stabilize or degrade proteins. While Astellas is initially focused on cancer, executives have said they see opportunities to use protein degraders in other settings such as immunology. The company also has an in-house candidate called ASP3082, a KRAS G12D degrader in phase 1 development for cancer. Astellas isn’t the only pharma that sees potential in protein degraders. Pfizer handed over $650 million upfront to Arvinas back in 2021 to develop and commercialize the biotech’s protein-degrading breast cancer drug. Meanwhile, Merck & Co. and Eli Lilly both secured their own partnerships with PeptiDream at the start of this year. PeptiDream’s Chief Operating Officer Keiichi Masuya said today’s agreement with Astellas “further validates the potential of our PDPS technology to obtain highly selective peptides, which enables creative approaches in the area of targeted protein degraders.”