On July 7, 2025 Inventiva (Euronext Paris and Nasdaq: IVA) ("Inventiva" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of oral therapies for the treatment of metabolic dysfunction-associated steatohepatitis ("MASH"), reported the receipt of a $10 million milestone payment from Chia Tai-Tianqing Pharmaceutical Group Co., Ltd ("CTTQ"), a subsidiary of Sino Biopharm (Press release, Inventiva Pharma, JUL 7, 2025, View Source [SID1234654260]).

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This milestone payment follows the successful settlement of the second tranche of €115.6 million1 in gross proceeds (net proceeds of €108.5 million) of the previously announced structured financing of up to €348 million2 (the "Structured Financing").

In September 2022, Inventiva entered into a licensing and collaboration agreement with CTTQ (as amended on October 11, 2024, the "CTTQ License Agreement") to develop and commercialize lanifibranor, Inventiva’s proprietary compound, for the treatment of MASH and potentially other metabolic diseases in Mainland China, Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan. Under the CTTQ License Agreement, Inventiva is eligible to receive up to an additional $265 million of clinical, regulatory and commercial milestone payments, as well as royalties in the low single digits on annual net sales of lanifibranor, if approved.

Based on the results from the Phase 2b NATIVE clinical trial, lanifibranor was granted Breakthrough Therapy Designation for MASH by the U.S. Food and Drug Administration in October 2020 and by the Chinese National Medical Products Administration (NMPA) in December 2023. This designation could potentially accelerate the development and regulatory review of drug candidates for serious or life-threatening conditions. CTTQ joined Inventiva’s ongoing NATiV3 pivotal Phase 3 clinical trial, which includes over 60 sites across mainland China. Furthermore, CTTQ has completed a Phase I bridging study and confirmed no significant ethnic differences, thereby paving the way to seek regulatory approval in China based on the results of the NATiV3 trial.

On July 7, 2025 ImmunityBio, Inc. (NASDAQ: IBRX) reported that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for ANKTIVA (nogapendekin alfa inbakicept-pmln) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of certain bladder cancer patients (Press release, ImmunityBio, JUL 7, 2025, View Source [SID1234654259]). This is the first marketing approval outside the U.S. for this novel lymphocyte-stimulating agent.

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"With the MHRA’s authorization of ANKTIVA plus BCG, we can now offer our immunotherapy outside the U.S. to help patients with a disease that, if not effectively treated, can lead to bladder removal," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "This immune-boosting, lymphocyte-stimulating agent, the first of its kind, is central to our Cancer BioShield platform, which is designed to restore immune function and support long-term disease control."

"ImmunityBio is honored to have received this important authorization from the UK MHRA. In light of the United States Most-Favored-Nation Prescription Drug Pricing policy implemented on May 12, 2025, we are actively evaluating our go-to-market strategy for the UK," said Richard Adcock, CEO and President of ImmunityBio.

ANKTIVA is a first-in-class IL-15 agonist that activates and proliferates natural killer (NK) cells and CD4+ and CD8+ T cells. It is designed to restore immune competence by reversing lymphopenia—a condition in which cancer and conventional therapies, such as chemotherapy, radiation and checkpoint inhibitors, reduce the number and function of immune cells. Restoring immune function is essential for immunosurveillance, immunogenic cell death, and sustained tumor control. The BioShield platform’s effectiveness can be monitored using a routine complete blood count (CBC).

ANKTIVA was designated a Breakthrough Therapy by the FDA and received approval from both the FDA and MHRA based on its safety and efficacy outcomes of complete response (CR) and duration of response (DOR). In a single-arm, multicenter trial, 77 evaluable patients received ANKTIVA with BCG for up to 37 months.

As of the November 2023 data cutoff, the duration of complete response for some patients exceeded 47 months and remains ongoing. These extended duration of complete responses beyond 24 months with ANKTIVA and BCG surpasses the benchmark for meaningful clinical results set by experts from the International Bladder Cancer Group.

ImmunityBio has also submitted regulatory applications to the European Medicines Agency (EMA) to expand availability of ANKTIVA across the 27 European Union (EU) member states, as well as Iceland, Norway and Liechtenstein.

About NMIBC CIS

Bladder cancer is the 10th most commonly-diagnosed cancer globally,2 and in the UK, the Action Bladder Cancer UK estimates approximately 23,000 patients are diagnosed annually.1 At the time of diagnosis, about 80% of cases are non-muscle invasive bladder cancer (NMIBC), wherein the cancer is found only on the inner layer of the bladder wall.3 The standard therapy for NMIBC is intravesical instillation (delivery to the bladder via a catheter) of bacillus Calmette-Guerin (BCG).4,5 BCG is a benign bacteria that induces an immune response in the bladder in proximity to the cancer cells, leading to clearance of the cancer in many patients. In ~30-40% of patients, however, BCG will fail, and in ~50% that initially respond, cancer will recur.6

About ANKTIVA

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.

ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo.

ANKTIVA was approved by the FDA in 2024 for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors. For more information, visit Anktiva.com.

Indication and Important Safety Information from the FDA Label

INDICATION AND USAGE: ANKTIVA is an interleukin-15 (IL-15) receptor agonist indicated with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

WARNINGS AND PRECAUTIONS: Risk of Metastatic Bladder Cancer with Delayed Cystectomy. Delaying cystectomy can lead to the development of muscle invasive or metastatic bladder cancer, which can be lethal. If patient with CIS do not have a complete response to treatment after a second induction course of ANKTIVA with BCG, reconsider cystectomy.

DOSAGE AND ADMINISTRATION: For lntravesical Use Only. Do not administer by subcutaneous or intravenous routes. Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours.

USE IN SPECIFIC POPULATIONS: Pregnancy: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

ADVERSE REACTIONS: The most common (≥15%) adverse reactions, including laboratory test abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia.

For more information about ANKTIVA, please see the Full Prescribing Information at www.anktiva.com.

You are encouraged to report negative side effects of prescription drugs to FDA.

Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact lmmunityBio at 1-877-ANKTIVA (1-877-265-8482)

On July 7, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519, hereafter "Chugai"), and Gero PTE. LTD. (hereafter "Gero"), a Singapore-based biotechnology company, reported that they have entered into a joint research and license agreement to develop novel therapies for age-related diseases (Press release, Chugai, JUL 7, 2025, View Source [SID1234654258]).

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In this collaboration, Chugai will create novel antibody drug candidates using its proprietary antibody engineering technologies for new drug targets discovered by Gero through analysis of human datasets using their unique AI target discovery platform. Under this agreement, Gero grants Chugai exclusive worldwide rights for the creation, research, development, manufacturing, and commercialization of antibodies for the identified targets. In addition to an upfront payment, Chugai will potentially pay up to approximately 250 million USD in total if predetermined development or sales milestones are achieved. If Chugai successfully launches a product, it will also pay royalties on sales to Gero.

"We believe that open innovation with external partners, including leading global players, is extremely important for achieving global first-class drug discovery outlined in our growth strategy toward 2030, TOP I 2030. By combining Gero’s target discovery technology with Chugai’s drug discovery technologies, we will accelerate the creation of innovation," said Chugai’s President and CEO, Dr. Osamu Okuda.

"Our AI platform is built to identify therapeutic targets that drive multiple age-related diseases and potentially aging itself," said Peter Fedichev, CEO of Gero. "In this collaboration, we aim to translate those insights into therapeutics that can help restore the lost function. This partnership with Chugai is an important step toward achieving Gero’s mission: to meaningfully target the biological processes of human aging."

"We are excited to partner with Chugai, a leading pharmaceutical company, to unlock the synergy between human data-driven target discovery and cutting-edge therapeutic design technology platforms. Together, we aim to develop first-in-class therapeutics to address unmet needs of increasing number of patients suffering from age-related diseases," said Alex Kadet, CBO of Gero.

On July 7, 2025 BeyondSpring Inc. (NASDAQ: BYSI) reported publication of a human clinical study in Med (Cell Press) demonstrating that Plinabulin, when combined with radiation and a checkpoint inhibitor, induces dendritic cell (DC) maturation and elicits tumor responses in patients across multiple cancer types who had failed prior ICI therapy (Press release, BeyondSpring Pharmaceuticals, JUL 7, 2025, View Source;utm_medium=rss&utm_campaign=beyondspring-publishes-human-clinical-study-in-med-cell-press-showing-plinabulin-driven-dendritic-cell-maturation-and-tumor-response-after-prior-checkpoint-inhibitor-failure [SID1234654257]). The study also identified a potential biomarker—baseline GEF-H1 immune signature—that may enable patient pre-selection and clinical response prediction.

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"These results offer early but important signals that Plinabulin’s dendritic cell maturation mechanism could play a pivotal role in reversing ICI-acquired resistance," said Dr. Steven Lin, M.D., Ph.D., corresponding author and Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. "The ability of Plinabulin to activate the immune system in this setting is both scientifically intriguing and clinically promising—particularly given the durability of responses in some heavily pretreated patients."

Dr. Lin added, "It is especially noteworthy that Plinabulin combination demonstrated the best responses in non-small cell lung cancer, head and neck squamous cell carcinoma, and Hodgkin lymphoma."

"This study builds upon the seminal work of Nobel Laureate Dr. Ralph Steinman and Dr. Ira Mellman, who helped define the essential role of dendritic cells in immune activation," said Lan Huang, Ph.D., Co-Founder, Chairman, and CEO of BeyondSpring. "Plinabulin’s ability to drive dendritic cell maturation and induce immune responsiveness offers a potential breakthrough strategy for patients who are refractory or relapsed on checkpoint inhibitors. We are committed to advancing Plinabulin’s development in partnership with pioneering cancer research institutions like MD Anderson."

Triple I/O Combination Study Highlights

This investigator-initiated, Phase 1 translational trial (NCT04902040) evaluated a triple immunotherapy approach combining Plinabulin, radiation (RT), and anti-PD-1 checkpoint inhibitors in patients with eight cancer types who are refractory or relapsed on prior ICI therapy. RT was administered only during the first cycle. The primary endpoint was tumor response in non-irradiated lesions.

Clinical Results
Nineteen patients received the combination regimen—14 on pembrolizumab and 5 on nivolumab. Tumor responses were evaluable in 13 ICI-relapsed patients across eight tumor types. Objective response rate (ORR) was 23%, and disease control rate (DCR) was 54%. Clinically meaningful benefits (PR, partial response; SD, stable disease) were observed in NSCLC (2/2), HNSCC (2/3), and Hodgkin lymphoma (2/2). Both Hodgkin lymphoma patients had durable responses exceeding 19 months despite 12–16 prior lines of therapy.
Mechanism Confirmation
Plinabulin triggered DC maturation post-RT via GEF-H1 signaling. Flow cytometry of whole blood revealed increased expression of DC maturation markers (CCR7, CD80, CD83) and a shift in monocyte subpopulations from classical to proinflammatory phenotype in responders.
Biomarker Insight
Single-cell RNA sequencing differentiated responders from non-responders and identified baseline GEF-H1 immune gene expression as a potential predictive biomarker for Plinabulin response.
About the Med Publication

Lin S.H., Subbiah V., Cohen E.N. et al. "Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers." Med. Published June 27, 2025. (View Source(25)00179-5)

About the Plinabulin Basket Study

This open-label, single-arm Phase 1 basket study (NCT04902040) at MD Anderson Cancer Center investigates safety and efficacy of Plinabulin plus radiation and PD-1 inhibitor in patients refractory or relapsed after prior immunotherapy. The primary endpoint is investigator-assessed ORR (RECIST 1.1) in non-irradiated lesions; secondary endpoints include DCR.

Regimen
– Radiation (Cycle 1 and optional Cycle 2): Local consolidative RT (8 Gy × 3; 12.5 Gy × 4; or 4 Gy × 5) on Day 1. Optional sequential RT in Cycle 2 at investigator discretion.
– Plinabulin: 30 mg/m² on Days 1 and 4 of Cycle 1 (3–6 hours post-RT); Day 1 of Cycle 2 onward; Additional Day 4 in Cycle 2 if RT is given in Cycle 2.
– PD-1 inhibitor: Pembrolizumab 200 mg on Day 1 every 21 days or nivolumab 240 mg on Day 1 every 14 days × 2 doses per cycle.
About Plinabulin

Plinabulin is a first-in-class dendritic cell maturation agent that binds reversibly to a unique site on tubulin, destabilizing microtubules in a controlled manner to release GEF-H1 (Chem 2019; Cell Reports 2019). Immune protein GEF-H1 activates the RhoA/ROCK signaling pathway, promoting dendritic cell maturation and anti-tumor T-cell immunity. This mechanism is distinct from traditional tubulin agents and does not interfere with tubulin stabilizers like docetaxel.

Across multiple clinical studies and approximately 800 patients, Plinabulin has shown durable anti-cancer activity and a favorable safety profile, and has significantly reduced chemotherapy-induced neutropenia, potentially enhancing docetaxel tolerability.

Prior Findings:
– In the Dublin-3 Phase 3 second and third line (2/3L) NSCLC, EGFR wild-type trial (n=559), Plinabulin + docetaxel demonstrated a significant overall survival benefit over standard-of-care docetaxel.
– In a Phase 2 study of Plinabulin + pembrolizumab + docetaxel in 2/3L NSCLC who progressed on PD-1/L1 inhibitors (n=47), median PFS was 6.8 months, and 15-month OS rate was 78%.

On July 4, 2025 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting Smart Allostery platform-identified regulatory sites on proteins referred to as "natural hotspots," reported the presentation of preclinical data from the Company’s CARD11-BCL10-MALT1 (CBM) signalosome program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2025 (Press release, HotSpot Therapeutics, JUL 4, 2025, View Source [SID1234654250]).

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The CBM signalosome is a molecular hub that serves as a key regulator of multiple oncogenic pathways, including NFkB, JNK, mTORC1 and MYC. As such, the CBM signalosome serves as a critical regulator of tumor development and survival, particularly in KRAS-driven colorectal cancer (CRC), as well as other KRAS-driven cancers, including pancreatic and lung cancer. Leveraging the Company’s proprietary Smart Allostery platform, HotSpot has discovered small molecule CBM signalosome inhibitors that bind and inactivate the complex, with preclinical data demonstrating dose-dependent tumor inhibition and regression in multiple KRAS-driven tumor models.

"While KRAS activation is a prominent genetic feature of CRC, KRAS inhibitors do not yield deep or durable responses for the vast majority of CRC patients. For the first time, we have shown that KRASG12X CRC depends on the CBM signalosome for survival, supporting the significant potential of a CBM signalosome inhibitor to transform the treatment landscape of KRASG12C CRC, as well as additional KRAS-associated solid tumors," said Geraldine Harriman, Ph.D., Chief Scientific Officer of HotSpot Therapeutics. "Leveraging our Smart Allostery platform, we have developed potent inhibitors of the CBM signalosome complex, with robust in vitro and in vivo data demonstrating apoptosis and tumor growth inhibition and regression in KRASG12C CRC, providing support for the profound clinical potential of a CBM signalosome inhibitor."

The poster presentations describe the following data:

HotSpot’s CBM signalosome inhibitors demonstrated selectively induced potent apoptosis in KRASG12 CRC cell lines, outperforming KRAS, BCL2 and Bcl-xL inhibitors.
In combination with a KRAS inhibitor, HotSpot’s CBM signalosome inhibitor achieved complete suppression of downstream signaling in KRASG12X cell lines.
HotSpot’s CBM signalosome inhibitor demonstrated dose-dependent tumor inhibition or regression both alone and in combination with a KRAS inhibitor in multiple in vivo models.