Arrivent BioPharma, Inc.

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here . Endpoints will be covering #ESMO24 throughout the weekend, so make sure to follow along online. Deputy editor Reynald Castañeda and reporters Kyle LaHucik, Lei Lei Wu and Ayisha Sharma will be reporting from Barcelona. — Max Gelman On Monday, the US House of Representatives passed the Biosecure Act with broad bipartisan support. The bill would force biopharma companies to cut ties or restrict their work with contract manufacturers WuXi AppTec , WuXi Biologics and three genetic sequencing companies by 2032. However, it still faces an uncertain future in the Senate. Opponents have argued that the bill was written to quickly and too broadly. Zachary Brennan has the latest. Biotech’s Covid-19 superstar has faced a rough go of it since the pandemic ended, saying since late last year that it would adopt a more “restrained” approach. But after leading off 2024 with $4 billion in expected cuts, Moderna said this week that it’s planning even more . Executives mapped out an additional $1.1 billion in cuts by 2027 and pushed back the company’s breakeven point by two years, from 2026 to 2028. Moderna’s stock is down more than 80% over the last three years. Our Andrew Dunn also framed how to think about this news in our Post-Hoc newsletter. Our reporters shared updates from #ESMO24, including lackluster data on Amgen’s PRMT5 inhibitor, a Phase 2 look at Jazz’s HER2 antibody, Bicycle’s early case for its Padcev competitor, mid-stage data for GSK and iTeos’ PD-1 and TIGIT doublet , and more. Stay tuned for more conference coverage throughout the weekend. In May, Summit surprised the industry by claiming its PD-1/VEGF bispecific antibody called ivonescimab beat Merck’s Keytruda in a head-to-head Phase 3 study. This Sunday, Summit backed up its case. Ivonescimab reduced the risk of lung cancer progression or death by 49% in the study, with patients going an average of 11.1 months before their disease worsened. Keytruda recorded an average of 5.8 months. Summit’s stock is up more than 800% since the May reveal, and more than 900% for the whole year. Friday afternoon, Jared Whitlock reported that the SEC’s probe of the Illumina-Grail deal is focused on sales forecasts made by Grail’s management in the run-up to the 2021 transaction. In June, Illumina spun off Grail and it began trading as a public company. We covered a string of early-stage GLP-1 readouts this week, including from Roche’s dual GLP-1/GIP candidate which showed promising weight loss, but also high rates of vomiting in a Phase 1b study . Terns also offered an early look at its oral GLP-1 agonist, which it says could be more tolerable at higher doses than currently marketed GLP-1s that are administered the same way. And Zealand’s GLP-1/GLP-2 receptor dual agonist showed promising weight loss after a previous effort with lower doses ended with “underwhelming” efficacy. SPOTLIGHT R&D PHARMA FINANCING FDA DEALS MANUFACTURING HEALTH TECH DON’T MISS

In what’s shaping up to be another slow year for biotech IPOs — better, however, than the 2022 and 2023 doldrums — Jim Healy is somewhat of an outlier. Only four biotechs from this year’s IPO class are trading above their debut pricings: CG Oncology, ArriVent BioPharma, Rapport Therapeutics and Contineum Therapeutics. Healy is on the boards of two of those: cancer drugmaker ArriVent, which is in late-stage testing with a drug out of a China-based partner; and neuroscience startup Rapport, which spun out of Johnson & Johnson and quickly raised successive megarounds before landing on the Nasdaq. The Sofinnova Investments managing partner, a self-described venture capitalist of about 25 years, is also on the board of BioAge Labs, an anti-aging and clinical-stage obesity startup that is also in the process of an IPO. He’s also on the Seaport Therapeutics board, alongside many other Karuna Therapeutics veterans, and sees potential for a quick run to the public markets at that neuropsychiatric biotech as well. “I’ve never really seen the markets close for high-quality companies that have good clinical data and a good development plan that they can execute,” Healy said in an interview on Wednesday. BioAge is one of four biotechs lined up for Wall Street entries in the coming days and weeks, including Bicara Therapeutics , Zenas BioPharma and MBX Biosciences . The market reaction to their debuts could set the tone on investor appetite for the backlog of biotechs looking for their shining moment in New York. “This current market feels like it’s much more selective in terms of the profile of companies that go public,” Healy said. All but one of this year’s class was clinical-stage when it rang the opening bell, he noted. “And if I look over a longer time frame, clinical-stage companies have outperformed their preclinical peers significantly over the past eight to nine years, so it feels like it’s a migration to quality.” For biotech companies to go public in this environment, Healy said it’s important they hone in on a lead asset, which is where private and public investors will place “a majority of the value.” “You can get incremental benefit for a second or third indication, or a second drug in the pipeline and the potential of a platform, but the vast majority of the value is assigned to the lead program or lead product,” he said. Biotech startups have reeled in large financings this year to ensure they get clinical data on their lead programs, rather than raise multiple smaller rounds at various checkpoints prior to the big readout. That has led the industry to go on a tear with megarounds this year, with F2G’s $100 million Series H Thursday morning marking the 71st such round of 2024, according to an Endpoints News tally. Access to capital is a big risk in biotech, Healy said, and investors want to decrease the refinancing risk, so they’ll raise larger rounds now with crossover investors who can help carry them to a public offering. One of the megarounds Sofinnova participated in this year, neuropsychiatric biotech Seaport, could be one such example. The clinical-stage startup derives from PureTech Health, the company that also launched Karuna, a schizophrenia drugmaker that Bristol Myers Squibb acquired for $14 billion. “If I look over our current funds, over the past two funds in particular or past five years, our average time to IPO is less than a year,” Healy said. “I would hope that Seaport would fit within our investment [strategy], and it would be outstanding if it could follow the trajectory that Karuna had. But of course, no guarantees.” Biotechs shouldn’t get over their skis. Median pre-money valuations have been about $475 million to $500 million this year and last. “I think companies that are doing private financings that put them well north of that create a challenge for themselves,” Healy said. “If you look at the current class of IPOs that have gone public, most have a step-up from their last private financing of around 1.2x, so one needs to consider that in the valuation as well.” Healy said the current market environment feels “much more rational.” “There’s a correlation between the stage of development and the enterprise value of companies,” he said.

81.8% ORR by BICR and 63.6% confirmed ORR by BICR at the 240 mg dose; 46.2% confirmed ORR in CNS Metastases 90.9% (n = 20/22) of patients with confirmed responses remained on study with a median duration of response not yet reached at time of analysis ArriVent to host virtual webinar on these interim analyses of Phase 1b data for firmonertinib in EGFR PACC mutant NSCLC on September 9, 2024 at 4:30 pm ET NEWTOWN SQUARE, Pa., Sept. 09, 2024 (GLOBE NEWSWIRE) -- ArriVent BioPharma, Inc. (Company or ArriVent) (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, today announced positive proof-of-concept randomized global Phase 1b FURTHER interim data for first-line firmonertinib monotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR PACC mutations at a Presidential Symposium Presentation at the IASCLC 2024 annual World Conference on Lung Cancer (WCLC), in San Diego, California. ArriVent plans to host a virtual webinar on September 9, 2024 at 4:30 pm ET. To register for the event, please click here. “These compelling dose-dependent interim data are the first to demonstrate robust systemic and CNS anti-tumor activity for firmonertinib in a PACC mutant population,” said Bing Yao, Chairman and Chief Executive Officer of ArriVent. “We believe that the generally well-tolerated safety profile and response duration seen to date reinforce the therapeutic potential of firmonertinib to be an effective oral, chemotherapy-free treatment for this underserved patient population. Importantly, these data add to the clinical body of evidence supporting firmonertinib as a potentially effective option across EGFR mutation types and lines of non-small cell lung cancer therapy.” Dr. Xiuning Le, Associate Professor of Thoracic Head and Neck Medical Oncology at MD Anderson Cancer Center and the lead Principal Investigator added, “Treating lung cancer patients with EGFR uncommon mutation lung cancer, including PACC mutations and Exon 20 insertion mutations, remains a clinical challenge, as we need more potent and better tolerated EGFR inhibitors. These encouraging randomized data for firmonertinib suggest rapid and robust anti-tumor activity across PACC mutations which is similar to that observed for firmonertinib in exon 20 insertions. Moreover, the apparent high CNS activity points to firmonertinib as a promising potential new therapy for frontline patients with PACC mutations including those with CNS disease.” Presidential Symposium Presentation HighlightsCurrent standards of care have improved outcomes for classical EGFR mutations but have been less effective against uncommon EGFR mutation types including PACC and Exon 20 insertion mutations which represent approximately 12% and 9% of NSCLC EGFR mutations, respectively. Firmonertinib, an oral, once-daily, highly brain-penetrant EGFR inhibitor with broad activity across EGFR mutations, was evaluated for interim clinical proof-of-concept data in first-line EGFR PACC mutant NSCLC as part of the Phase 1b FURTHER trial. Select clinical activity and safety results from FURTHER interim data analysis include: First clinical dataset from an EGFR inhibitor being tested in a randomized defined population of EGFR PACC mutant NSCLCRobust systemic and central nervous system (CNS) responses across patients observed as of June 20, 2024 (data cut): 81.8% at 240mg and 47.8% at 160mg overall response rate (ORR) by blinded independent central review (BICR)63.6% and 34.8% confirmed ORR by BICR at 240mg and 160mg dose levels, respectively. One unconfirmed partial response pending confirmation at each of the 160mg and 240mg dose levels.Median duration of response had not yet been reached; 90.9% (n = 20/22) patients with confirmed responses remain on study46.2% (n = 6/13) CNS confirmed ORR by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by BICR in first-line patients with brain metastases at baseline Generally well-tolerated with a profile consistent with prior firmonertinib data Most frequent treatment-related adverse events (TRAEs) were diarrhea, rash, dry skin, stomatitis, and hepatic enzyme elevationNo treatment discontinuation due to TRAEs was observed Firmonertinib showed promising dose-dependent activity in NSCLC patients across a broad range of EGFR PACC mutations in the first-line metastatic setting and includes CNS antitumor activity consistent with its high brain penetrance. About ArriVentArriVent is a clinical-stage biopharmaceutical company dedicated to the identification, development, and commercialization of differentiated medicines to address the unmet medical needs of patients with cancers. ArriVent seeks to utilize its team’s deep drug development experience to maximize the potential of its lead development candidate, firmonertinib, and advance a pipeline of novel therapeutics, such as next-generation antibody drug conjugates, through approval and commercialization. About FirmonertinibFirmonertinib (formerly furmonertinib) is an oral, highly brain-penetrant, and broadly active mutation-selective epidermal growth factor receptor (EGFR) inhibitor active against both classical and uncommon EGFR mutations, including PACC and exon 20 insertion mutations. In March 2021, firmonertinib was approved in China for first-line advanced non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletion or L858R mutations and for patients with previously treated locally advanced or metastatic NSCLC with EGFR T790M mutation, otherwise known as EGFR classical mutations. Firmonertinib was granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for the treatment of patients with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. Firmonertinib was also granted FDA Orphan Drug Designation for the treatment of non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations or human epidermal growth factor receptor 2 (HER2) mutations or HER4 mutations. Firmonertinib is currently being studied in a global Phase 3 trial for first-line NSCLC patients with EGFR exon 20 insertion mutations (FURVENT; NCT05607550) and in a global Phase 1b study, which includes a cohort evaluating firmonertinib in patients with EGFR PACC mutations (FURTHER; NCT05364073). In addition, firmonertinib is also being studied in a clinical combination study targeting advanced or metastatic NSCLC patients with EGFR classical mutations, in partnership with Beijing InnoCare Pharma Tech Co., Ltd. About EGFR mutant NSCLCGlobally, lung cancer is the leading cause of cancer-related deaths among men and women. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases. Mutational activation of the EGFR is a frequent and early event in the development of NSCLC. EGFR mutations are divided into classical and uncommon. EGFR exon 20 insertion mutations are a group of uncommon EGFR mutations and constitute approximately 9% of all EGFR mutations. PACC mutations are another group of uncommon EGFR mutations and represent approximately 12% of all EGFR mutations. Patients with NSCLC whose tumors harbor uncommon EGFR mutations have significantly lower life expectancy with available therapies and represent an area of unmet medical need. Forward-Looking StatementsThis press release includes certain disclosures that contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations or financial condition, business strategy and plans, activity of firmonertinib compared to available therapies, anticipated clinical milestones, including proof of concept data for firmonertinib in patients with NSCLC EGFR PACC mutations, top-line pivotal Phase 3 data for firmonertinib in previously untreated NSCLC patients whose tumors contain EGFR exon 20 insertion mutations, and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Forward-looking statements are based on ArriVent’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties that are described more fully in the section titled “Risk Factors” in our annual report on Form 10-K for the fiscal year ended December 31, 2023, filed with the Securities and Exchange Commission on March 28, 2024 and our other filings with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and ArriVent undertakes no duty to update such information except as required under applicable law. Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com