On July 12, 2024 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its self-developed novel Nectin-4-targeting ADC (R&D Code: 9MW2821) has been granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic Nectin-4 positive triple negative breast cancer (TNBC) (Press release, Mabwell Biotech, JUL 12, 2024, View Source [SID1234644808]).

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The FDA’s FTD is intended to expedite the development and review of pharmaceuticals used to treat critical conditions, therefore speeding up the process of bringing these drugs to market. Therapeutics with Fast Track Designation are likely to obtain priority evaluation and speedy approval if they meet the appropriate criteria.

9MW2821 has received multiple regulatory designations from the FDA within just 6 months. Prior to this, 9MW2821 has been granted FTD for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) and recurrent or metastatic cervical cancer (CC) progressed on or following prior treatment with a platinum-based chemotherapy regimen, and also granted Orphan Drug Designation (ODD) for the treatment of esophageal cancer (EC), highlighting its potential and innovation in treating multiple tumors. These designations not only accelerate the development process of 9MW2821 but also lay the groundwork for its potential future priority review.

About 9MW2821

9MW2821 is the first site-specific conjugated novel Nectin-4-targeting ADC developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies, and the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data of CC, EC and breast cancer. 9MW2821 has been granted FTD by FDA for the treatment of advanced, recurrent, or metastatic ESCC in Feb. 2024, and also respectively granted ODD and FTD for the treatment of esophageal cancer and recurrent or metastatic CC progressed on or following prior treatment with a platinum-based chemotherapy regimen in May 2024. Then, it has been granted FTD for the treatment of locally advanced or metastatic Nectin-4 positive TNBC in July, 2024.

9MW2821 achieves site-specific modification of antibody through proprietary conjugate technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.

On July 12, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported positive results from Cohort B of the TACTI-003 (KEYNOTE-PNC-34) Phase IIb trial evaluating eftilagimod alfa (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with negative PD-L1 expression (Press release, Immutep, JUL 12, 2024, View Source [SID1234644807]). The updated efficacy and safety data was presented by Dr. Robert Metcalf during an oral presentation at the ESMO (Free ESMO Whitepaper) Virtual Plenary session at 18:30-19:30 CEST on 11 July 2024.

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Results
The investigational immuno-oncology (IO) combination utilising efti and KEYTRUDA achieved an objective response rate (ORR) of 35.5% (11 of 31 evaluable patients) and a disease control rate (DCR) of 58.1%, according to RECIST 1.1, in 1L HNSCC patients whose tumours do not express PD-L1 (Combined Positive Score [CPS] <1). These results are among the highest recorded for a chemotherapy-free approach in negative PD-L1 patients and compare favourably to a historical control of 5.4% ORR and 32.4% DCR from anti-PD-1 monotherapy.1

Additionally, the IO combination attained a high complete response rate of 9.7% (3 of 31 patients), which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1.2 Notably, one patient with early progressive disease according to RECIST 1.1 has evolved into a confirmed partial responder who remains on therapy after 14 months, resulting in a 38.7% ORR for the IO-combination, according to iRECIST.

Robert Metcalf, MD, PhD, The Christie NHS Foundation Trust, Manchester, U.K., stated, "The high response rate from this novel immunotherapy combination is well above other treatment approaches without chemotherapy. It matches historical response rates from chemotherapy-based treatments but without the associated toxicities. This is really significant for patients with head and neck squamous cell carcinomas who have a CPS less than one and for whom chemotherapy is the current first line treatment. Achieving complete responses in this group bodes well for this immunotherapy combination’s future potential, especially given the positive trend in response durability. The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population."

Durability of Responses and Favourable Safety
Durability of responses is tracking well as has been seen in other clinical trials when efti is combined with KEYTRUDA. Over 50% of patients in Cohort B received treatment for at least six months with three additional patients nearing this threshold at the time of data cut off (11 March 2024). The combination also continues to have a favourable safety profile with no new safety signals observed.

This new data adds to the body of evidence that efti’s novel activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors such as KEYTRUDA. Importantly, as the only MHC Class II agonist in clinical development today, efti is generating a broad anti-cancer immune response in a unique and safe manner across all levels of PD-L1 expression, especially in patients with negative expression (CPS <1).

Next Steps
Based on the encouraging efficacy and high unmet medical need, Immutep will discuss the path forward with regulatory agencies. Efti has received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression. The prevalence for CPS <1, CPS 1-19, and CPS >20 PD-L1 expression levels are approximately 20%, 30%, and 50% of the HNSCC patient population, respectively.3

Webcast Details
Immutep will host a webcast to discuss the clinical data. A replay of the webcast will be available under the Events section of Immutep’s website after the event.

Date/Time: Friday, July 12, at 9am AEST (7pm ET July 11)
Register: Link to register for webcast
Questions: Investors are invited to submit questions in advance via [email protected]

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the TACTI-003 Trial
The TACTI-003 (KEYNOTE-PNC-34) trial is an ongoing Phase IIb study evaluating eftilagimod alfa (efti), Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with pembrolizumab as compared to pembrolizumab monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with pembrolizumab in patients with PD-L1 negative tumours.

The primary endpoint of the study is Overall Response Rate of evaluable patients according to RECIST 1.1. Secondary endpoints include Overall Survival, Overall Response Rate according to iRECIST, Progression Free Survival, and Duration of Response. For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).

About Eftilagimod Alfa (Efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

On July 12, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that the first patient has been dosed in a Phase 1/2 trial in China, conducted by GenFleet Therapeutics, evaluating GFH375/VS-7375, a KRAS G12D (ON/OFF) inhibitor (Press release, Verastem, JUL 12, 2024, View Source [SID1234644806]).

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GFH375/VS-7375, was selected as Verastem’s lead discovery program from its collaboration with GenFleet established in 2023. GFH375/VS-7375 is an oral, potent and selective KRAS G12D dual inhibitor of ON (GTP) and OFF (GDP) states. Preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024 demonstrated oral bioavailability across preclinical species, strong anti-tumor activity as a single agent and potency against intracranial tumor models suggesting the potential to treat brain metastases.

"In a short amount of time, we identified GFH375/VS-7375, a novel KRAS G12D (ON/OFF) inhibitor, as our lead discovery program last year and now the first patient has been dosed in the Phase 1/2 study by GenFleet in China," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We look forward to leveraging the initial clinical dose escalation data to accelerate our development path in the U.S., as there are currently no FDA-approved KRAS G12D-targeted treatments despite the high prevalence of this KRAS mutation in various cancers, including pancreatic, colorectal, lung and uterine."

The Phase 1 study is being conducted in approximately 20 hospitals currently in China and will evaluate the safety and efficacy of GFH375/VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose (RP2D) and then further evaluate in Phase 2 the efficacy and safety of GFH375/VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer and non-small cell lung cancer.

About GFH375/VS-7375

GFH375/VS-7375 is a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead discovery program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for GFH375/VS-7375 was approved in China in June 2024 and the Phase 1/2 trial in KRAS G12D-mutant solid tumors was subsequently initiated and the first patient has been dosed in July 2024. The collaboration includes three discovery programs, the first being the KRAS G12D inhibitor, and provides Verastem Oncology with exclusive options to license three compounds selected for collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

On July 12, 2024 EORTC reported that the primary endpoint has been reached in the EORTC-1333-GUCG/PEACE III Trial (Press release, EORTC, JUL 12, 2024, View Source [SID1234644802]).

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The phase III EORTC-1333-GUCG/PEACE III trial is a randomised multicentre phase III trial comparing enzalutamide vs. a combination of radium-223 dichloride and enzalutamide in asymptomatic or mildly symptomatic castration resistant prostate cancer patients metastatic to bone.

The full results will be presented at an upcoming medical meeting.

We extend our gratitude to the patients, investigators, and research teams who participated in the EORTC-1333-GUCG/PEACE III Trial and made this achievement possible.

This trial is supported by an investigator driven clinical trial agreement from Bayer HealthCare Pharmaceuticals Inc. and Astellas Pharma Europe. This trial is a collaboration between EORTC, UNICANCER, Clinical Trial Ireland (CTI), Canadian Urological Oncology Group (CUOG) and Latin American Cooperative Oncology Group (LACOG).

View Source

On July 12, 2024 Phio Pharmaceuticals Corp., a Delaware corporation (the "Company") reported the company entered into inducement letter agreements (the "Inducement Letter Agreements") with certain holders (the "Holders") of certain of its existing warrants to purchase up to an aggregate of 545,286 shares of the Company’s common stock, $0.0001 par value (the "Common Stock"), originally issued to the Holders in February 2020 through December 2023, having exercise prices between $324.00 and $9.72 per share (the "Existing Warrants") (Filing, Phio Pharmaceuticals, JUL 12, 2024, View Source [SID1234644805]).

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The shares of Common Stock issuable upon exercise of the Existing Warrants are registered pursuant to effective registration statements on Form S-1 (Nos. 333-239779, 333-234032, 333-238204, 333-271521, 333-272526 and 333-276146) and Form S-3 (No. 333-252588).

Pursuant to the Inducement Letter Agreements, the Holders agreed to exercise for cash the Existing Warrants at a reduced exercise price of $5.45 per share in consideration of the Company’s agreement to issue new unregistered Series C Warrants (the "Series C Warrants") to purchase up to 583,098 shares of Common Stock and new unregistered Series D Warrants (the "Series D Warrants" and, together with the Series C Warrants, the "New Warrants") to purchase up to 507,474 shares of Common Stock (collectively, the "New Warrant Shares"), issued and sold at a price of $0.125 per New Warrant. The Series C Warrants will have an exercise price of $5.45 per share, will be exercisable immediately upon issuance and have a term equal to five and one-half years from the date of issuance. The Series D Warrants will have an exercise price of $5.45 per share, will be exercisable immediately upon issuance and have a term equal to eighteen months from the date of issuance.

The Company has agreed to file a registration statement providing for the resale of the New Warrant Shares issuable upon the exercise of the New Warrants (the "Resale Registration Statement"), within 20 calendar days from the date of the Inducement Letter Agreements. Pursuant to the Inducement Letter Agreements, the Company agreed not to issue, enter into any agreement to issue or announce the issuance or proposed issuance of any Common Stock or Common Stock equivalents or file any registration statement or any amendment or supplement to any existing registration statement (other than the Resale Registration Statement contemplated by the Inducement Letter Agreements and described above) until the earlier of (i) a period of 90 calendar days after the closing of the offering and (ii) the day following the date that the Company’s closing price on five consecutive trading days equals or exceeds $6.50 (each of which shall be after 30 calendar days after the closing of the offering).

The gross proceeds to the Company from the exercise of the warrants are expected to be approximately $3.1 million, prior to deducting placement agent fees and estimated offering expenses. The closing of the offering occurred on July 12, 2024.

On June 27, 2024, the Company entered into an engagement letter with H.C. Wainwright & Co., LLC ("Wainwright"), pursuant to which Wainwright agreed, among other things, to serve as the exclusive placement agent for the Company, on a reasonable best-efforts basis, in connection with the above-mentioned transaction. The Company will pay Wainwright (i) an aggregate cash fee equal to 7.5% of the gross proceeds from the exercise of the Existing Warrants and, if the New Warrants are exercised for cash, upon such exercise, and (ii) a management fee equal to 1.0% of the aggregate gross proceeds from the exercise of the Existing Warrants and, if the New Warrants are exercised for cash, upon such exercise. In connection with the above-mentioned offering, the Company also agreed to pay Wainwright $35,000 for non-accountable expenses, $50,000 for accountable expenses and $15,950 for clearing fees. Additionally, in connection with the above-mentioned offering, the Company agreed to issue to Wainwright or its designees as compensation, warrants to purchase up to 40,896 shares of Common Stock, equal to 7.5% of the aggregate number of Existing Warrants exercised in the offering and, if the New Warrants are exercised for cash, further warrants to purchase shares of Common Stock equal to the 7.5% of the aggregate number of New Warrants so exercised (the "Placement Agent Warrants"). The Placement Agent Warrants have or will have a term of five and one half years from the closing of the offering or the exercise of the New Warrants, as applicable, and an exercise price of $6.8125 per share of Common Stock.

The foregoing summaries of the Inducement Letter Agreements, the New Warrants and the Placement Agent Warrants do not purport to be complete and are subject to, and qualified in their entirety by, the forms of such documents attached as Exhibits 10.1, 4.1, and 4.2, respectively, to this Current Report on Form 8-K, which are incorporated herein by reference.