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Dizal’s ZEGFROVY® (sunvozertinib) Receives FDA Accelerated Approval as the Only Targeted Oral Treatment for Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

On July 2, 2025 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported that the U.S. Food and Drug Administration (FDA) has approved ZEGFROVY (sunvozertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins), as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy (Press release, Dizal Pharma, JUL 2, 2025, View Source [SID1234654226]).

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ZEGFROVY, which has received Priority Review and Breakthrough Therapy Designation from the FDA, is the only approved targeted oral treatment for NSCLC with EGFR exon20ins. This indication is approved under Accelerated Approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

"We are proud to have developed ZEGFROVY, a first-in-class oral therapy that offers a more effective treatment option with enhanced safety and ease of administration for NSCLC patients with EGFR exon20ins," said Dr. Xiaolin Zhang, CEO of Dizal. "The accelerated approval of ZEGFROVY marks a significant milestone that underscores our commitment to developing groundbreaking new medicines for patients with high unmet medical needs around the world."

ZEGFROVY is an oral, irreversible EGFR inhibitor with uniquely designed molecular structure targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, ZEGFROVY received accelerated approval in China. Today’s FDA approval follows Breakthrough Therapy Designation and Priority Review granted by both the U.S. FDA and the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA).

The FDA approval is supported by data from the multinational pivotal study WU-KONG1 Part B (WU-KONG1B), aiming to investigate the efficacy and safety of ZEGFROVY in relapsed or refractory NSCLC with EGFR exon20ins. The study results were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and were accepted to publish in the Journal of Clinical Oncology.

"As the world’s only approved targeted oral therapy for EGFR exon20ins NSCLC, ZEGFROVY has expanded the treatment paradigm in this therapeutic area that has long lacked convenient and effective treatment options," said Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute of Harvard Medical School and lead principal investigator of WU-KONG1B. "Research findings from WU-KONG1B have demonstrated ZEGFROVY’s significant therapeutic effects with consistent efficacy across both Asian and non-Asian patient populations. Its convenient once-daily oral dosing substantially improves administration convenience and patient adherence, which is an increasingly critical factor as lung cancer care shifts toward chronic disease management. The U.S. approval of ZEGFROVY marks a landmark in scientific advancement and represents a meaningful milestone in addressing the long-standing unmet medical needs of this underserved patient population."

"ZEGFROVY has demonstrated breakthrough therapeutic value in the treatment of EGFR exon20ins NSCLC, as shown in a rigorous multinational clinical trial. Its potent antitumor activity, manageable safety profile, and convenient oral administration position it as an optimal treatment option in clinical practice," said Prof. James Chih-Hsin Yang, MD, PhD, National Taiwan University Cancer Center Hospital and the Co-lead principal investigator of WU-KONG1B. "The approval of ZEGFROVY in major global markets not only offers new hope for patients, but also reinforces our commitment to patient-centered research and the continued advancement of precision medicine in lung cancer."

"In NSCLC, EGFR exon20ins represent the third most common type of EGFR mutation. EGFR exon20ins are particularly challenging to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. As a result, patients face a poor prognosis and limited treatment options," said Prof. Mengzhao Wang, MD, PhD, lead principal investigator of the China-based pivotal study WU-KONG6 of ZEGFROVY and principal investigator of WU-KONG1B at Peking Union Medical College Hospital, "The results of the WU-KONG6 study demonstrated ZEGFROVY’s clinical benefit superior to current options and lead to the drug’s approval in China. The U.S. approval of ZEGFROVY will enable more patients around the world to benefit from this drug."

The FDA simultaneously approved Thermo Fisher Scientific’s Oncomine Dx Express Test as a next-generation sequencing (NGS) companion diagnostic (CDx) for ZEGFROVY to identify NSCLC patients with EGFR Exon20 insertions. NGS testing is recognized as a critical technology in cancer genomic profiling, facilitating the rapid and precise detection of DNA mutations in tumor cells. Combined with the Ion Torrent Genexus Dx System, the test delivers NGS results in as little as 24 hours to help inform more timely treatment decisions in patients with EGFR exon20ins NSCLC.

Additionally, Dizal has completed enrollment for its multinational phase III pivotal WU-KONG28 study, evaluating ZEGFROVY versus platinum-based doublet chemotherapies in treatment naïve NSCLC patients with EGFR exon20ins across 16 countries and regions. At the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting, Dizal reported that ZEGFROVY, as a single oral agent, achieved a confirmed objective response rate (ORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in the first-line setting. With its potent antitumor activity and favorable safety profile, ZEGFROVY demonstrated strong potential as an optimal first-line treatment for patients with EGFR exon20ins NSCLC.

About ZEGFROVY (sunvozertinib)

ZEGFROVY is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. ZEGFROVY is approved in the U.S. and China for the treatment the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins), whose disease has progressed on or after platinum-based chemotherapy. The China approval is based on the results of the pivotal WU-KONG6 study in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The U.S. approval is supported by WU-KONG1 Part B, a multinational pivotal study investigating the efficacy and safety of ZEGFROVY in the same indication.

In addition, ZEGFROVY also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

ZEGFROVY showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

WU-KONG28, a phase III, multinational, randomized study assessing ZEGFROVY as a first-line treatment for patients with EGFR exon20ins NSCLC, has completed enrollment across 16 countries and regions.

Pre-clinical and clinical results of ZEGFROVY were published in peer-reviewed journals Cancer Discovery, The Lancet Respiratory Medicine.

Jacobio’s IND for Phase I/II Clinical Trial of BET Inhibitor JAB-8263 in Autoimmune Diseases has been Accepted

On July 2, 2025 Jacobio Pharma (1167.HK) reported that it has submitted the Phase I/II Investigational New Drug (IND) application for its BET inhibitor JAB-8263 for the treatment of autoimmune diseases to the Center for Drug Evaluation (CDE) in China and has been accepted (Press release, Jacobio Pharmaceuticals, JUL 2, 2025, View Source [SID1234654225]). According to new regulatory guidelines, the review of JAB-8263’s IND application is expected to be completed within 30 working days

Dr. Yinxiang Wang, Chairman and CEO of Jacobio, said: "Autoimmune diseases affect 5%-9% of the global population. Currently, the majority of therapies are monoclonal antibodies administered intravenously, with only a few oral drugs approved. Through our internal translation research and discovery efforts, we intend to expand the therapeutic value of our BET inhibitor from oncology to autoimmune diseases, ultimately benefiting a broader patient population."

Previously, Jacobio has completed phase I clinical trials of JAB-8263 for solid tumor and hematological malignancies in both China and the United States. Data presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showed that JAB-8263 demonstrated good tolerability.

About JAB-8263

JAB-8263 is an orally administered, highly potent BET inhibitor independently developed by Jacobio Pharma. Its safety and pharmacokinetics have been evaluated in early phase trials in China and the United States. JAB-8263 was well tolerated and exhibited a favorable PK profile. Jacobio is investigating the potential of JAB-8263 in solid tumors and autoimmune diseases.

INOVIO Announces Proposed Public Offering

On July 2, 2025 INOVIO Pharmaceuticals, Inc. (Nasdaq: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported that it intends to offer and sell shares of its common stock (or pre-funded warrants to purchase its common stock in lieu thereof) and in either case, accompanying Series A warrants and Series B warrants to purchase shares of its common stock (or pre-funded warrants to purchase its common stock in lieu thereof), in an underwritten public offering (Press release, Inovio, JUL 2, 2025, View Source [SID1234654224]). All of the securities in the proposed offering will be sold by INOVIO. INOVIO intends to grant the underwriter a 30-day option to purchase additional shares of its common stock and/or accompanying Series A and Series B warrants to purchase shares of its common stock in an amount up to 15% of the securities offered in the public offering under the same terms and conditions. The proposed offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

Piper Sandler & Co. is acting as sole book-running manager for the offering.

A shelf registration statement relating to the shares of common stock, pre-funded warrants and accompanying Series A and Series B warrants offered in the offering described above was filed with the Securities and Exchange Commission ("SEC") on November 9, 2023 and declared effective by the SEC on January 31, 2024. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting: Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, or by telephone at (800) 747-3924, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

Tonix Pharmaceuticals Announces Peer-Reviewed Publication in Cancer Cell Journal Highlighting Positive Preclinical Data of mTNX-1700 in Gastric Cancer Animal Models

On July 2, 2025 Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, reported the publication of a paper entitled, "A CXCR4 Partial Agonist, Improves Immunotherapy by Targeting Immunosuppressive Neutrophils and Cancer-Driven Granulopoiesis,"1 in the peer-reviewed journal Cancer Cell, that represents a collaboration between scientists at Tonix and Columbia University’s Medical School and presents data demonstrating that treatment with murine TNX-1700 (mTNX-1700) increased survival and decreased metastases in animal models of gastric cancer (Press release, TONIX Pharmaceuticals, JUL 2, 2025, View Source [SID1234654223]). The manuscript can be accessed here: http://bit.ly/3I7Wcvu.

"Addressing the root causes of resistance to immunotherapy in solid tumors is a hurdle for the successful application of immuno-oncology to anti-PD-1 resistant cancers," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "The combination therapy of mTFF2-MSA with anti-PD1 treatment shows significant promise in reducing the ability of tumors to evade anti-PD-1 therapy in animal models. We believe the published data support further development of TNX-1700 as an approach to overcome resistance to anti-PD-1 immunotherapy in the treatment of gastric cancer and other tumors."

The published studies examined mTNX-1700, which is a fusion protein of murine trefoil factor-2 (mTFF2) and murine serum albumin (MSA). The human version, TNX-1700 is a fusion protein of human TFF2 (hTFF2) and human serum albumin (HSA) that is under development for the treatment of gastric and colorectal cancers.

Dr. Lederman added, "The study showed that in several mouse models, mTNX-1700 plus anti-PD-1 shrank primary tumors, cut liver and lung metastases, and increased survival compared to anti-PD-1 alone. These data show that fine-tuned modulation of CXCR4 can dismantle neutrophil-driven immune suppression and revive checkpoint efficacy without compromising normal myelopoiesis. We are excited, through our collaboration with Columbia University, to continue studies to identify potential clinical biomarkers through preclinical models while enhancing our understanding of the relationship between the role of TFF2 in overcoming resistance to anti-PD1 therapy in the tumor microenvironment (TME)."

Immunosuppressive neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor activity2,3. Despite being short-lived, the continuous replenishment of PMN-MDSCs from the bone marrow sustains their potent immunosuppression in the TME4. Stromal cells in the TME promote immunosuppression by recruiting MDSCs via secretion of CXCL12. Trefoil Factor 2 (TFF2), a secreted peptide of the trefoil factor family, has displayed activity as a partial agonist of CXCR45,6. The Cancer Cell publication describes data demonstrating that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. Treatment with TFF2-MSA, in combination with an anti-PD1 antibody, induced robust anti-tumoral CD8+ T cell responses, inhibiting tumor invasion. This combination of the mTNX-1700 with anti-PD1 therapy has been shown to reduce tumor size and increase survival in these animal models. TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs levels while promoting a T-cell rich microenvironment and inducing an increase in CD8+ T cells in the tumor.

About Trefoil Factor Family Member 2 (TFF2)

Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 for the treatment of gastric and colorectal cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth. Dr. Wang proposed the concept of employing recombinant TFF2 in combination with other therapies in cancer prevention and early treatment.

Lynozyfic™ (linvoseltamab-gcpt) Receives FDA Accelerated Approval for Treatment of Relapsed or Refractory Multiple Myeloma

On July 2, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Lynozyfic (linvoseltamab-gcpt) to treat adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti‑CD38 monoclonal antibody (Press release, Regeneron, JUL 2, 2025, View Source [SID1234654222]). Lynozyfic was granted accelerated approval based on response rate and durability of response in the LINKER-MM1 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Lynozyfic is the first FDA-approved BCMAxCD3 bispecific antibody that can be dosed every two weeks starting at week 14, and every four weeks if a very good partial response (VGPR) or better is achieved following completion of at least 24 weeks of therapy. The regimen includes hospitalization for safety during the step-up dosing period (one 24-hour period after the first step-up dose, and another 24-hour period after the second step-up dose).

"The FDA approval of Lynozyfic represents meaningful progress for the multiple myeloma community. Lynozyfic demonstrated early, deep and durable responses in heavily pre-treated patients, which I saw firsthand in clinical trials," said Sundar Jagannath, M.D., Network Director of the Center of Excellence for Multiple Myeloma at Mount Sinai in New York City and a trial investigator. "Lynozyfic has a convenient response-adapted dosing regimen, which provides the potential to extend time between doses. This is a significant patient-centric advancement that could help reduce treatment burden."

The FDA approval is based on results from the pivotal Phase 1/2 LINKER-MM1 trial investigating linvoseltamab in R/R MM in which patients (n=80) experienced a:

70% objective response rate (ORR), with 45% achieving a complete response (CR) or better, as determined by an independent review committee.
0.95 month median time to first response (range: 0.5 to 6 months).
Median duration of response (DoR) that was not reached (95% Confidence Interval [CI]: 12 months to not estimable). The estimated DoR was 89% at 9 months (95% CI: 77 to 95 months) and 72% at 12 months (95% CI: 54 to 84 months) among responders who had a median follow-up of 13 months.

The prescribing information for Lynozyfic has a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity – including immune effector cell-associated neurotoxicity syndrome – in addition to warnings and precautions for infections, neutropenia, hepatotoxicity and embryo-fetal toxicity. The most common adverse reactions (≥20%) in the safety population of LINKER-MM1 (n=117) were musculoskeletal pain, CRS, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache and dyspnea. The most common Grade 3 or 4 laboratory abnormalities (≥30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin and decreased white blood cell count. Lynozyfic is available only through a restricted program called the Lynozyfic Risk Evaluation and Mitigation Strategy (REMS). Details of the Important Safety Information are included below.

"The FDA approval of Lynozyfic reinforces the strength of our bispecific antibody program as well as our commitment to delivering critical medicines to the cancer community," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "With a 70% overall response rate in heavily pre-treated patients, we believe Lynozyfic is poised to potentially become a new standard of care for multiple myeloma. Furthermore, given the strength of the data, we are rapidly advancing our broad clinical development program for Lynozyfic – exploring its use in earlier lines of therapy as monotherapy and in novel combinations – as we aim to meaningfully advance care for patients."

Regeneron is committed to helping patients who have been prescribed Lynozyfic access their medication. The company has launched Lynozyfic Surround, which offers financial and educational resources to help support patients throughout their treatment journey. For more information, patients can call 1-844-RGN-HEME (1-844-746-4363).

"Even though the number of treatment options for multiple myeloma has expanded in recent years, it remains an incurable disease with considerable unmet need, especially among patients who have undergone multiple lines of treatment," said Diane Moran, R.N., M.A., Ed.M., Chief Executive Officer (Interim) and Senior Vice President of Strategic Planning at the International Myeloma Foundation. "The FDA approval of Lynozyfic is a welcome milestone. It provides appropriate multiple myeloma patients and their care teams with a novel patient-centric treatment option that includes a dosing schedule that can be adapted based on patient response. We appreciate Regeneron’s continued research to further advance treatment for this community."

About Multiple Myeloma

As the second most common blood cancer, there are over 187,000 new cases of MM diagnosed globally every year, with more than 36,000 diagnosed and 12,000 deaths anticipated in the U.S. in 2025. In the U.S., there are approximately 8,000 people who have MM that has progressed after three lines of therapy, and 4,000 whose disease has progressed after four or more therapies.

The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About Lynozyfic (linvoseltamab-gcpt)

Lynozyfic was invented using Regeneron’s VelocImmune technology and is a fully human BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. At week 14, patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve and maintain a VGPR or better after having completed at least 24 weeks of therapy. Patients should be hospitalized for 24 hours after administration of the first step-up dose and for 24 hours after administration of the second step-up dose, with the potential for additional hospitalization if patients experience certain adverse events.

The generic name for Lynozyfic in its approved U.S. indication is linvoseltamab-gcpt with gcpt as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Outside of the U.S., the generic name of Lynozyfic in its approved indications is linvoseltamab. Lynozyfic is also approved in the European Union to treat adults with R/R MM after at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu in due course.

About the Linvoseltamab Clinical Development Program

The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in more than 300 enrolled patients with R/R MM. The Phase 1 intravenous dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. A subcutaneous Phase 1 portion is ongoing. The Phase 2 intravenous dose expansion portion is ongoing and assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of ORR. Key secondary endpoints include DoR, progression-free survival, rate of minimum residual disease negative status and overall survival.

Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as MM precursor and other plasma cell disorders. This includes evaluating linvoseltamab in a Phase 1b trial (LINKER-MM2) in combination with other cancer treatments in R/R MM as well as a Phase 3 confirmatory trial (LINKER-MM3) as a monotherapy in R/R MM. For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 1-844-734-6643.