Positive phase 3 readouts from AstraZeneca and Daiichi Sankyo's Dato-DXd along with the Padcev-Keytruda combo made our news this week. Dato-DXd, the TROP2-targeted antibody-drug conjugate in development by AstraZeneca and Daiichi Sankyo, has hits its goal in a breast cancer trial. Plus, the combination of Padcev and Keytruda succeeded in a broad first-line bladder cancer setting. AbbVie has officially terminated its CD47 collaboration with I-Mab. And more. 1. AstraZeneca, Daiichi hit first goal in pivotal breast cancer ADC trial, teeing up filings to challenge Gilead AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan has beaten chemotherapy at delaying disease progression or death in previously treated HR-positive, HER2-low or negative breast cancer in a phase 3 trial. The drug also showed a favorable trend toward life extension, although the data were immature on that marker. If approved, the drug would compete with Gilead Sciences' anti-TROP2 antibody-drug conjugate Trodelvy. 2. Seagen and Astellas' Padcev, in Keytruda combo, delivers 'practice-changing' bladder cancer win Meanwhile, the closely watched EV-302 trial has yielded a win for the combination of Seagen and Astellas’ Padcev and Merck’s Keytruda. The combo topped chemotherapy on both overall survival and progression-free survival in previously untreated metastatic bladder cancer. The positive trial could serve to convert the combo’s accelerated approval in platinum-ineligible patients and expand it into the platinum-eligible group. 3. AbbVie axes I-Mab pact to exit fast-thinning race for CD47 space AbbVie has officially abandoned I-Mab’s anti-CD47 antibody lemzoparlimab more than a year after nixing a pair of clinical trials in blood cancers. The deal was originally worth nearly $2 billion, with $180 million upfront. I-Mab is still studying the drug in China, with a phase 3 study ongoing in myelodysplastic syndrome. 4. Takeda snaps $580M for shot at pick 6 with AcuraStem's PIKFYVE ALS target Takeda has in-licensed the PIKFYVE-targeted amyotrophic lateral sclerosis pipeline at AcuraStem in a deal potentially worth $580 million. The package includes a preclinical antisense oligonucleotide coded AS-202. AcuraStem suggests targeting the PIKFYVE kinase may also be relevant for treating other diseases such as frontotemporal dementia. 5. Merck and Eisai's Keytruda-Lenvima combo chalks up 2 more losses, this time in non-small cell lung cancer Merck and Eisai’s Lenvima-Keytruda combo has failed two more trials. Adding Lenvima to Keytruda and chemo didn’t move the needle for patients with first-line nonsquamous non-small cell lung cancer (NSCLC) in the LEAP-006 trial. In the LEAP-008 trial, the Lenvima-Keytruda regimen couldn’t beat chemo in NSCLC patients who progressed on chemo and anti-PD-1/L1 treatment. 6. Coherus hits FDA hurdles for PD-1 drug, Neulasta biosimilar on-body injector Junshi Biosciences’ China-made PD-1 inhibitor toripalimab has hit another FDA hurdle. After a preapproval inspection, the FDA flagged a problem at a clinical trial site in China for toripalimab’s application in nasopharyngeal carcinoma. Junshi’s U.S. partner Coherus BioSciences said the single observation is “readily addressable” and that the pair still expects an approval by year-end. 7. NICE poised to reject AstraZeneca, Daiichi’s Enhertu in HER2-low breast cancer Enhertu’s efficacy in HER2-low breast cancer isn’t worth its price for coverage in England, the National Institute for Health and Care Excellence (NICE) ruled in draft guidance. While recognizing the AstraZeneca and Daiichi Sankyo drug is a “potentially significant development” for patients, NICE and the drugmakers clashed on the economic model. 8. Glenmark solves its 'decade-long' debt problem with $681M sale of API unit to Nirma Glenmark is selling 75% of its active pharmaceutical ingredient business to Nirma limited for RS 5,651 crore ($681 million). The deal will cover Glenmark’s debt of about RS 4,600 crore, which was described by a local news outlet as a “decade-long troubled affair.” The API unit represents a relatively high profit margin driver within Glenmark. Other News of Note 9. J&J inks 'first of its kind' pact with Singapore government to boost regional life sciences innovation 10. Strides to spin off its CDMO and softgel businesses into single group with 1,200 employees 11. WuXi debuts first vaccine CDMO site in China, where it plans to employ more than 500 12. Eisai wins Japan nod for Alzheimer’s drug Leqembi as Lilly files donanemab (tracker)

Phase 3VaccineClinical Result

29 Sep 2023

·www.biospace.com

Path for BrainStorm ALS Treatment Remains Rocky, Hope for Others on Horizon

Pictured: Boy in orange shirt sitting in a wheelchair at the beach/iStock, ChiccoDodiFC Amyotrophic lateral sclerosis (ALS), known as Lou Gehrig’s disease, dominated this week’s news. An FDA advisory committee met on Wednesday to consider BrainStorm Cell Therapeutics’ much-debated experimental treatment NurOwn. The adcomm voted 17-1 that NurOwn did not demonstrate substantial evidence of effectiveness in mild to moderate ALS. However, the near unanimous adcomm vote against BrainStorm’s candidate was not surprising. In briefing documents published Monday, ahead of Wednesday’s meeting, the FDA took issue with the cell therapy’s manufacturing plan and said BrainStorm failed to demonstrate substantial evidence of efficacy in its Biologics License Application. Further, the agency said that upon initial receipt of the BLA, it determined it was “scientifically incomplete” to demonstrate effectiveness, while the manufacturing information it received was “grossly deficient” to ensure adequate quality of the product. Though Wednesday’s adcomm panelists expressed compassion for ALS patients, they pointed to “conflicting” information and a “lack of efficacy” in terms of survival and statistical evidence that didn’t meet the regulatory requirement. The one vote in favor of BrainStorm’s NurOwn came from Kathleen O’Sullivan-Fortin, founder of ALD Connect, who said “there’s no bigger risk than imminent certain deaths from ALS and these are unique and desperate circumstances that would require us to exercise flexibility.” In the U.S., there are approximately 25,000 people living with ALS, a fatal neurodegenerative disease that damages nerve cells in the brain and spinal cord. While ALS has no cure and there is no effective treatment to reverse its progression, there are more than half a dozen drugs approved by the FDA to treat the neurological disorder and its symptoms. However, there is a pipeline of potential candidates on the horizon. Clene reported this week that the company’s experimental drug reduced the risk of death by 49% compared to the largest U.S. database of previous ALS therapy trials. “Improved survival status is an important measure of drug effect,” Merit Cudkowicz, chair of the neurology department at Massachusetts General Hospital and principal investigator of the HEALEY ALS Platform Trial, said in a statement. Also, Seelos Therapeutics’ SLS-005 (Trehalose) is being evaluated in the HEALEY ALS Platform Trial, which is examining the effectiveness of the candidate at stabilizing proteins and promoting autophagy in the brain to clear toxic protein aggregations characteristic of ALS. Top-line data from the registrational Phase II/III trial is expected before the end of 2023. It is among four late-stage Neurodegenerative Trials to Watch in Q4. Takeda this week pledged up to $580 million in a development and commercialization deal with AcuraStem for the latter’s PIKFYVE program for ALS. The Japanese multinational pharma will gain access to AcuraStem’s PIKFYVE program, which includes AS-202, an investigational antisense oligonucleotide and the biotech’s most mature candidate. PIKFYVE is an emerging therapeutic target in ALS and Takeda now has exclusive worldwide license to AS-202 as well as to AcuraStem’s other PIKFYVE-directed assets. Greg Slabodkin is the News Editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.

Cell TherapyOligonucleotideClinical Study

26 Sep 2023

·www.fiercebiotech.com

Takeda snaps $580M for shot at pick 6 with AcuraStem's PIKFYVE ALS target

Researchers recently showed another PIKFYVE inhibitor prompted motor neurons to clear out toxic proteins. With scientific research this year continuing to point to the potential of the PIKFYVE enzyme as a target for amyotrophic lateral sclerosis (ALS), Takeda has decided to join the team. Some of the main players in the PIKFYVE space are Verge Genomics, AI Therapeutics and AcuraStem, and Takeda has opted for the latter. The Japanese drugmaker has acquired the exclusive worldwide license to AcuraStem’s PIKFYVE-targeted ALS program, including a preclinical antisense oligonucleotide dubbed AS-202. AcuraStem will oversee some of the work to get AS-202 through investigational new drug-enabling studies as well as prep some potential backup antisense oligonucleotides before Takeda takes any resulting drugs through the clinic and hopefully to market. The exact financial makeup of the deal is less clear, with AcuraStem only revealing that the combined upfront payment and milestones could reach $580 million in total, alongside royalties. A study in February published in Cell was a timely reminder of the potential of PIKFYVE as a target for ALS therapy. Researchers used a drug from AI Therapeutics called apilimod to inhibit PIKFYVE in human motor neurons, roundworms, fruit flies and mice with ALS. The drug prompted motor neurons to clear out toxic proteins, improving motor function and extending survival in all the models, the researchers reported. While progress has been made on drugs to treat genetic ALS, researchers have struggled to find therapies that work well in the second and far more common type, known as sporadic ALS. The difficulties with getting new treatments to market was hammered home again yesterday by the FDA’s methodical takedown of BrainStorm Cell Therapeutics' approval application for its NurOwn drug ahead of an advisory committee meeting later this week. “Whilst recent treatment advances have brought new hope to some patients, there remains a significant unmet need [in ALS],” Sarah Sheikh, head of Takeda’s neuroscience unit, said in the Sept. 25 release. “We believe AS-202 has the potential to address this unmet need through its unique dual mechanism of action, which addresses TDP-43 aggregation and improves TDP-43 function, the pathological hallmark of ALS and other TDP-43 proteinopathies including certain forms of dementia,” Sheikh added. The unmet need by ALS patients for more therapies has drawn in Eli Lilly and, more recently, AstraZeneca, which have both secured deals with Verge Genomics to work on new neurodegenerative drugs. However, neither deal touched on the biotech’s own small-molecule PIKFYVE inhibitor called VRG50635, which is in a phase 1 trial for ALS.

License out/inPhase 1Oligonucleotide

100 Deals associated with AS-202

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Preclinical	US	Acurastem, Inc.Startup	-
Frontotemporal Dementia	Discovery	US	Acurastem, Inc.Startup	-

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