Shanghai Allist Pharmaceuticals Co., Ltd.

Aside from Summit Therapeutics’ shocking win over Merck’s Keytruda, here’s what else you need to know from the World Conference on Lung Cancer, which is currently underway in San Diego: ArriVent BioPharma shared early-stage results from an experimental drug in certain lung cancer patients with a mutation called EGFR PACC that has been relatively understudied. The company said Monday that its dataset is the first for an EGFR inhibitor being tested in a randomized defined population of non-small cell lung cancer patients with this mutation. In the Phase 1b FURTHER study, 60 patients were randomized to receive either a 240 mg or 160 mg dose of firmonertinib, an EGFR inhibitor approved in China for advanced lung cancer patients with certain mutations. ArriVent licensed the drug from Shanghai Allist Pharmaceuticals in 2021. ArriVent believes that firmonertinib’s broad activity can make it effective in indications for which AstraZeneca’s blockbuster Tagrisso has not been approved. In 22 first-line patients who received the high dose, 14 saw their tumors shrink by at least 30% — good for a confirmed response rate of 63.6%. In 23 first-line patients who received the low dose, eight responded, resulting in a 34.8% response rate. ArriVent said that there is one additional unconfirmed partial response at each dose level. “Because PACC mutation is such an under-understood disease space and is such an under-investigated mutation, the practice currently is very heterogeneous in Europe, in China and other parts of Asia and in the US. Physicians pick different standard-of-care choices, so the randomization to which control arm is still an active discussion,” Xiuning Le, a thoracic medical oncologist and associate professor at the University of Texas MD Anderson Cancer Center, said during a press conference when asked about further studies of the drug in PACC-mutated lung cancer. According to ArriVent’s presentation, PACC mutations account for roughly 12.5% of EGFR mutations and are similar to exon 20 insertion mutations. ArriVent CEO Bing Yao noted that physicians may prescribe Tagrisso off-label for these patients. ArriVent also shared data showing the drug could reach brain metastases in a handful of patients. “Most importantly, this molecule has really good brain penetration,” Yao said, noting that 30% of patients have brain metastases when they are first diagnosed and 70% will develop them over the course of the disease. The company is currently studying the drug in the Phase 3 FURVENT trial for patients with EGFR exon 20 mutations, for which Tagrisso is not approved. Boehringer Ingelheim also revealed results on Monday from a Phase 1b study of its HER2-specific tyrosine kinase inhibitor that is being developed for HER2-mutated non-small cell lung cancer. In 75 patients who received a 120 mg dose of zongertinib, the confirmed response rate was 66.7%, and Boehringer Ingelheim also said that preliminary activity of the drug against brain metastases was seen. The therapy was designed to spare wild-type EGFR to reduce toxicities. “While these mutations are rare, they are critical drivers in a subset of non-small cell lung cancer cases, and current treatment options are severely limited. Patients with this type of cancer typically face a poor prognosis, with approximately 50% responding to first-line treatment and only 20% responding to second-line therapy,” John Heymach, the study’s principal investigator and an oncologist at MD Anderson, said in a statement . A Phase 3 study called Beamion LUNG-2 is looking at zongertinib as a first-line treatment for advanced lung cancer with activating HER2 mutations. It is currently enrolling. Plus, news from AstraZeneca and Bayer:

Astellas' Eccles plant closure and a new R&D center, plus a Chinese investigation into some AstraZeneca staffers made our news this week. Astellas is closing a gene therapy manufacturing facility in South San Francisco. But, across the country, the company opened a new R&D center in Massachusetts. Chinese authorities detained several current or former AstraZeneca employees. And more.1. Astellas Gene Therapies to turn out the lights at South San Francisco production plantAstellas’ gene therapy branch is closing its Eccles manufacturing facility in South San Francisco. All existing programs at the plant will be moved to another site in Sanford, North Carolina. While the fate of the California site’s 100 employees wasn’t immediately clear, at least 17 staffers are being let go, according to two public notices.2. Astellas unveils Massachusetts lab that will be shared with biotechs, academia researchersAstellas has opened a new life sciences collaboration hub in Massachusetts. Besides about 400 Astellas employees who will work there, the center includes the Japanese pharma’s first U.S.-based SakuLab, which will be shared with external partners. The location also houses a small-molecule unit focused on targeted protein degradation research.3. AstraZeneca staffers detained in China over patient data collection, drug imports: BloombergFive current and former employees in AstraZeneca’s oncology division have been detained in China, the company confirmed. Bloomberg, citing people familiar with the matter, reports that the investigation centers around a possible violation of data privacy laws and potential illegal importation of an unapproved liver cancer drug. The latest investigation follows an insurance fraud case involving AZ in the country about three years ago.4. Glenmark joins growing list of drugmakers to settle long-running US price-fixing claimsGlenmark has agreed to pay the U.S. Department of Justice $25 million to resolve allegations that it colluded with other drugmakers to rig the price and market around the cholesterol med pravastatin. The payment is separate from $30 million in criminal penalties that the generics maker paid last year as part of a deferred prosecution agreement.5. DEA raises production limits on Takeda's ADHD drug Vyvanse and generics as shortages continueAmid an ongoing shortage, the U.S. Drug Enforcement Administration has increased production limits on Takeda’s ADHD drug Vyvanse and lisdexamfetamine generics by 24%. Not all increases are being allocated for U.S. domestic demand. Takeda reported “low inventory” for Vyvanse in June 2023 thanks to increased demand and a manufacturing delay.6. BIOSECURE Act heads for possible vote in House of Representatives next weekThe U.S. House of Representatives has added the BIOSECURE Act to a list of legislation that it plans to consider during the week of Sept. 9. As for the Senate, the most promising path forward would be for it to be folded into the annual defense policy this year. The House version recently added a grace period for biotech companies to cut ties with Chinese service providers.Other News of Note:7. FDA scrutiny of India’s Zydus results in warning letter8. Dr. Reddy's banned from China's drug procurement program after inspectors turn up manufacturing problems9. Allist pays Jacobio $21M for KRAS drug combo, landing leading role in Chinese cancer race10. Takeda taps longtime FleishmanHillard alum to head up global corporate brand and content11. Daiichi study finds gender inequality in European cardiovascular care12. EpimAb licenses BCMA bispecific to Vignette in $635M biobucks deal (release)

Schizophrenia patients can suffer from both positive and negative symptoms. Credit: Drawlab19 via Shutterstock. Japanese biopharma Nxera Pharma has secured $35m in milestone payments from Neurocrine Biosciences following positive Phase II trial data of NBI-1117568 (NBI-568) in adults with schizophrenia. The two companies teamed up in November 2021 to develop novel muscarinic receptor antagonists. Nxera – which has a portfolio of muscarinic receptor agonists – could secure up to $2.6bn in total from its partnership with Neurocrine, along with product royalties. Neurocrine reported positive data from the Phase II dose-finding study last week, highlighting that the study met its primary endpoint with a significant reduction in schizophrenia symptoms at a once-daily 20mg dose. The trial also demonstrated a clinically meaningful and statistically significant decline in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week six. The current treatment landscape for schizophrenia is dominated by dopamine-blocking antipsychotics, which have significant side effects such as Parkinsonian symptoms, sexual dysfunction, and weight gain. There has been a push in the space for a new class of medication, that can target both the positive and negative symptoms of schizophrenia. The positive symptoms refer to any change in behaviour or thoughts, such as hallucinations or delusions. Negative symptoms include a lack of interest in everyday social interactions, low mood, and the appearance of withdrawal from normal life. See Also: Aptose Biosciences secures funds for AML treatment development Jacobio Pharma grants Allist rights to two assets in China NBI-568 is an oral, muscarinic M4 selective agonist. It is thought to alleviate both positive and negative symptoms of schizophrenia by influencing dopamine signalling. Neurocrine now plans to advance the candidate into Phase III clinical trials in early 2025. According to GlobalData forecasters, NBI-568 could generate up to $202m in sales in 2030 if it secured approval. GlobalData is the parent company of Pharmaceutical Technology. Elsewhere in the space, all eyes move to Bristol Myers Squibb’s (BMS’) KarXT as potential US Food and Drug Administration (FDA) approval looms. The Prescription Drug User Fee Act (PDUFA) date for KarXT is 26 September 2024. If approved , the drug would represent a new class of medication on offer to those with schizophrenia. In the announcement accompanying the payment, Nxera’s UK president and R&D head Matt Barnes said: “The successful Phase II trial with NBI-568 delivered positive data in adults with schizophrenia at the 20mg dose. “As stated by Neurocrine, these data support advancing NBI-568 into Phase III trials that would aim to confirm its potential to become a new oral therapy option for patients with a competitive profile based on efficacy, safety, and tolerability from a convenient 20mg once-daily administration.”