On November 5, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported the completion of patient enrollment of SAFFRON, a global Phase III study of ORPATHYS (savolitinib) and TAGRISSO (osimertinib) for the treatment of patients with epidermal growth factor receptor ("EGFR")-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic non-small cell lung cancer ("NSCLC") following progression on treatment with TAGRISSO. The last patient was randomized on October 31, 2025.

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This combination represents a promising, chemotherapy-free, all-oral treatment option following progression on an EGFR tyrosine kinase inhibitor ("TKI"), and was granted approval in China in June 2025 based on the results of the SACHI randomized Phase III trial. ORPATHYS is an oral, potent and highly selective MET TKI being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. TAGRISSO is a third-generation, irreversible EGFR TKI.

SAFFRON is a global Phase III, open-label, randomized, multicenter study to investigate the efficacy and safety of ORPATHYS administered orally in combination with TAGRISSO versus platinum-based doublet chemotherapy in participants with EGFR-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with TAGRISSO as the most recent therapy. The primary endpoint of the study is progression free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST 1.1 criteria. Other endpoints include overall survival (OS), objective response rate ("ORR"), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety. This study randomized 338 patients, screened from over 230 sites across 29 countries. Additional details may be found at clinicaltrials.gov, using identifier NCT05261399.

Topline results from the SAFFRON study are estimated to be reported in the first half of 2026, followed by submission of results for presentation at an appropriate medical congress. If favorable, the results could support global regulatory filings for the ORPATHYS and TAGRISSO combination.

About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.[1] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.[2] The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and up to 40-50% of patients in Asia have EGFR-mutated ("EGFRm") NSCLC.[3],[4],[5],[6],[7]

MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of de novo or acquired resistance to EGFR TKI for metastatic EGFRm NSCLC.[8],[9]

About ORPATHYS
ORPATHYS (savolitinib) is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS is approved in China and is marketed by AstraZeneca for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations, representing the first selective MET inhibitor approved in China. ORPATHYS is also approved in China for the treatment of patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification after disease progression on EGFR tyrosine kinase inhibitor therapy, in combination with TAGRISSO.

It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines.

About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with ORPATHYS (savolitinib) in the SAFFRON Phase III trial and in combination with DATROWAY (datopotamab deruxtecan or Dato-DXd) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

About ORPATHYS and TAGRISSO Combination Development in EGFR-mutated NSCLC
This combination represents a promising chemotherapy-free oral treatment strategy to address mechanisms of resistance in this setting. Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with ORPATHYS in combination with TAGRISSO has been studied extensively in these patients in the TATTON study (NCT02143466) and the SAVANNAH single-arm Phase II study (NCT03778229). Strong data from SAVANNAH presented at the 2025 European Lung Cancer Congress (ELCC) demonstrated high, clinically meaningful and durable ORR, with consistent safety results. The encouraging results led to the initiation of several randomized Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836).

SACHI: This Phase III trial in China evaluated the combination of ORPATHYS and TAGRISSO compared to platinum-based doublet chemotherapy for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC following progression on treatment with an EGFR TKI. Results were presented at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting. The treatment combination received approval in China in June 2025.

SAFFRON: This ongoing global Phase III trial is to evaluate the combination of ORPATHYS and TAGRISSO compared to platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on treatment with TAGRISSO. This received Fast Track Designation from the US Food and Drug Administration (FDA) and enrollment was completed in October 2025. We look forward to completing this trial to support potential US and other global registration filings.

SANOVO: This ongoing Phase III trial in China is to evaluate the combination of ORPATHYS and TAGRISSO compared to TAGRISSO monotherapy in previously untreated patients with locally advanced or metastatic NSCLC with EGFRm and MET overexpression. Enrollment was completed in August 2025.

(Press release, Hutchison China MediTech, NOV 5, 2025, https://www.hutch-med.com/saffron-global-phiii-enrollment-completion/ [SID1234659385])

On November 04, 2025 Azalea Therapeutics, Inc., a biotechnology company redefining precision genomic medicines in vivo, reported its official launch and completion of $82 million in seed and Series A financing to advance its proprietary Enveloped Delivery Vehicle (EDV) technology. The company’s mission is to engineer therapeutic cells with precision directly inside the patient, transforming how cell and gene therapies are created and delivered.

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Azalea’s EDV technology selectively targets cells, delivering transient CRISPR-Cas9 cargo to mediate programmable genome editing. Combining this with a highly efficient T cell-tropic AAV to deliver a promoterless homology-directed repair template enables programmable, site-specific large gene insertion at defined genomic sites within the T cell. This dual-vector platform provides multiple layers of precision by achieving cell- and genomic site-specific gene insertion under regulatory control of a native promoter, with the potential to increase durability, efficacy and safety. Azalea has utilized this approach to insert chimeric antigen receptor (CAR) genes under an endogenous, T cell-restricted promoter in vivo – enabling durable therapeutic benefit while eliminating the need for ex vivo manufacturing and lymphodepletion. Together, these advances enable precise engineering of functional CAR-T cells within a patient – a monumental advancement in the fields of cell and gene therapy.

"At Azalea, we are aiming to make cell therapy as simple as dosing a medicine," said Jenny Hamilton, Ph.D., co-founder, president and chief executive officer of Azalea Therapeutics. "By combining cell-selective delivery with site-specific genome integration, we can create potent and durable in vivo CAR-T and other cell-based therapies inside the body and extend the reach of genome engineering to many more patients."

The $82 million funding, which includes a recently closed $65 million Series A financing, was led by Third Rock Ventures, with participation from RA Capital Management, Yosemite, Sozo Ventures and select individual investors. Funds will be used to advance Azalea’s CD19-based in vivo CAR-T therapy for B cell malignancies and autoimmune diseases through IND-enabling studies and into the clinic, progress its BCMA-targeted in vivo CAR-T program for multiple myeloma and an undisclosed program for solid tumors, while exploring expansion of the platform to other cell types.

Currently based at UC Berkeley’s Bakar Bio Labs, Azalea grew out of collaborative research conducted at the Innovative Genomics Institute in Dr. Jennifer Doudna’s laboratory and in Dr. Justin Eyquem’s laboratory at UC San Francisco, as part of the Gladstone/UCSF Institute for Genomic Immunology. The early academic work was supported by philanthropic grants from the Yosemite team and the Parker Institute for Cancer Immunotherapy to support early de-risking, and Azalea’s company launch was supported by a $1 million non-dilutive award from the HS Chau Women in Enterprising Science program, which fosters the translation of breakthrough academic research into biotech startups.

Together with Dr. Hamilton, Azalea’s co-founders bring deep academic and translational expertise across genome engineering, synthetic biology and cell therapy, including:

Jennifer Doudna, Ph.D., the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and professor of molecular and cell biology at UC Berkeley, Howard Hughes Medical Institute Investigator, founder of the Innovative Genomics Institute and 2020 Nobel laureate in chemistry
Michael Fischbach, Ph.D., the Liu (Liao) Family Professor of Bioengineering at Stanford University, institute scholar of Stanford ChEM-H and director of the Stanford Microbiome Therapies Initiative
Justin Eyquem, Ph.D., associate professor of medicine in the Division of Hematology and Oncology at UCSF, affiliate investigator at Gladstone Institutes and member of the Parker Institute for Cancer Immunotherapy
"Azalea is advancing a powerful concept – delivering precision genome editing tools to specific cells inside the body," said Justin Eyquem, Ph.D. "The ability to directly engineer cells in vivo opens new possibilities for treating disease and for bringing genomic medicines to patients in a safer and more scalable way."

Together with its distinguished scientific founders, Azalea is supported by leading biotech investors committed to advancing the company’s vision.

"Azalea is at the forefront of realizing in vivo CAR-T cell therapy – combining scientific excellence with bold execution to make precise in-patient cell engineering a reality," said Andrea van Elsas, Ph.D., board director of Azalea and partner at Third Rock Ventures. "The team is uniquely positioned to deliver on the promise of off-the-shelf genome engineering with curative intent and a clear path toward the clinic."

Azalea will present its latest data on Thursday, November 20th at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Breakthroughs in Targeted In Vivo Gene Editing, taking place virtually and in San Diego.

Abstract Title: In vivo generation of TRAC CAR-T cells by leveraging enveloped delivery vehicles
Presenting Author: Jenny Hamilton, Ph.D., Azalea Therapeutics
Session 5: Oral Abstracts
Date/Time: Thursday, November 20, 2025 | 3:45 – 5:00 pm PST

Visit the ASGCT (Free ASGCT Whitepaper) Breakthroughs in Targeted In Vivo Gene Editing website to view the published abstracts.

Azalea’s leadership and board bring deep scientific, operational and investment expertise spanning genome engineering, cell therapy and company building:

Leadership
Jenny Hamilton, Ph.D. – co-founder, president and chief executive officer
Paul Westberg, MBA – chief business officer
Connor Tsuchida, Ph.D. – scientific co-founder
Abdullah Syed, Ph.D. – scientific co-founder

Board of Directors
Andrea van Elsas, Ph.D. – partner, Third Rock Ventures
Mary Lynne Hedley, Ph.D. – venture partner, Third Rock Ventures
Nandita Shangari, Ph.D. – managing director, RA Capital Management
Michael Fischbach, Ph.D. – professor of bioengineering, Stanford University
Justin Eyquem, Ph.D. – associate professor of medicine, UCSF
Jenny Hamilton, Ph.D. – co-founder and chief executive officer

Board Observers
Jennifer Doudna, Ph.D. – professor of molecular and cell biology at UC Berkeley
Reed Jobs, M.A. – investor, Yosemite
Jenna Hebert, Ph.D. – investment director, RA Capital Management

(Press release, Azalea Therapeutics, NOV 4, 2025, View Source [SID1234663808])

On November 4, 2025 Crescent Biopharma, Inc. ("Crescent" or the "Company") (Nasdaq: CBIO), a biotechnology company dedicated to rapidly advancing the next wave of therapies for cancer patients, reported that preclinical data from CR-001, its PD-1 x VEGF bispecific antibody being developed for solid tumors, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 40th Annual Meeting being held November 7-9, 2025 in National Harbor, Maryland.

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CR-001 is a tetravalent bispecific antibody combining two complementary, validated mechanisms in oncology via a blockade of PD-1 and VEGF. In data to be presented at SITC (Free SITC Whitepaper), CR-001 demonstrated cooperative pharmacology in vitro with increased binding to PD-1 in the presence of VEGF, augmenting the PD-1/PD-L1 signaling blockade and enhancing T-cell activation. This cooperativity was consistent with preclinical evaluation of ivonescimab, another tetravalent PD-1 x VEGF bispecific antibody, which demonstrated superior efficacy compared to the current market leader, pembrolizumab, in a large, third-party Phase 3 trial in non-small cell lung cancer.1,2 CR-001 also showed potent anti-tumor activity in a xenograft mouse model, and was well-tolerated in non-human primates after a single intravenous dose with robust PD-1 receptor occupancy.

"These data highlight the cooperative mechanism of CR-001 and its ability to reduce tumor growth in vivo, reinforcing its potential as a next generation immuno-oncology therapy," said Jan Pinkas, Ph.D., chief scientific officer of Crescent. "We are on track to advance CR-001 into the clinic and plan to initiate our global Phase 1 trial in patients with solid tumors in the first quarter of 2026."

Details of the poster presentation are as follows:

Title: Preclinical development of CR-001, a novel tetravalent PD-1 x VEGF bispecific antibody with cooperative pharmacology and potent anti-tumor activity
Abstract Number: 1185
Presentation Date: Friday, November 7, 2025
Location: Prince George ABC Exhibit Halls, Gaylord National Resort and Convention Center

The abstract is available on SITC (Free SITC Whitepaper)’s website ahead of the presentation. The poster will be available in the Presentations & Publications section of Crescent’s website beginning at 9:00 a.m. ET on the day of the presentation.

About CR-001

CR-001 is a tetravalent bispecific antibody being developed for the treatment of solid tumors that combines two complementary, validated mechanisms in oncology via a blockade of PD-1 and VEGF. PD-1 checkpoint inhibition is aimed at restoring T cells’ ability to recognize and destroy tumor cells, and blocking VEGF is intended for reducing blood supply to tumor cells and inhibiting tumor growth. In preclinical studies, CR-001 demonstrated cooperative pharmacology with increased binding to PD-1 and signal blockade in the presence of VEGF as well as robust anti-tumor activity. CR-001’s anti-VEGF activity may also normalize the vasculature at the tumor site, which has the potential to improve the localization and effectiveness of combination therapies, such as the administration of CR-001 with Crescent’s antibody-drug conjugates (ADCs) in development.

(Press release, Crescent Biopharma, NOV 4, 2025, View Source [SID1234663683])

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On November 4, 2025 Relmada Therapeutics, Inc. (Nasdaq: RLMD, "Relmada" or the "Company"), a clinical-stage biotechnology company advancing innovative therapies for oncology and central nervous system indications, reported the pricing of its underwritten offering of 40,142,000 shares of its common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase up to 5,315,000 shares of common stock. The shares of common stock are being sold at an offering price of $2.20 per share, and the pre-funded warrants are being sold at an offering price of $2.199 per pre-funded warrant, which represents the per share offering price for the common stock less the $0.001 per share exercise price for each such pre-funded warrant. The gross proceeds to Relmada from the offering, before deducting underwriting discounts and commissions and other expenses payable by Relmada, and excluding the exercise of any pre-funded warrants, are expected to be approximately $100 million. The offering is expected to close on November 5, 2025, subject to customary closing conditions. Investors in the offering included Janus Henderson Investors, Ferring Ventures SA, Squadron Capital Management, Marshall Wace, Spruce Street Capital, OrbiMed, Columbia Threadneedle Investments and Driehaus Capital Management.

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Jefferies and Leerink Partners are acting as joint book-running managers for the offering. Mizuho is acting as book-runner for the offering.

Relmada intends to use the net proceeds from the offering, together with existing cash, cash equivalents, and short-term investments, for working capital and general corporate purposes, which includes, without limitation, clinical studies required to gain regulatory approvals, implementation of adequate systems and controls to allow for regulatory approvals, further development of its product candidates, investing in or acquiring companies that are synergistic with or complementary to its technologies, licensing activities related to its current and future product candidates, the development of emerging technologies, investing in or acquiring companies that are developing emerging technologies, licensing activities, or the acquisition of other businesses.

The securities described above were offered by Relmada pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was declared effective by the Securities and Exchange Commission ("SEC") on September 12, 2024. A final prospectus supplement describing the terms of the offering will be filed with the SEC. Copies of the final prospectus supplement and the accompanying base prospectus, when available, may also be obtained by request by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, New York 10022, or by telephone at (877) 821-7388, or by e-mail at [email protected]; Leerink Partners LLC, Syndicate Department, 53 State Street, 40th Floor, Boston, Massachusetts 02109, by telephone at (800) 808-7525 ext. 6105, or by emailing [email protected]; or Mizuho Securities USA LLC, Attention: Equity Capital Markets Desk, at 1271 Avenue of the Americas, New York, New York 10020, or by email at [email protected].

This press release is for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of any securities of Relmada, in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

(Press release, Relmada Therapeutics, NOV 4, 2025, View Source [SID1234661916])