On July 3, 2024 Pulse Biosciences, Inc. (Nasdaq: PLSE) (the "Company" or "Pulse Biosciences"), a company leveraging its novel and proprietary CellFX Nanosecond Pulsed Field Ablation (nsPFA) technology, reported the closing of its rights offering and the final results thereof (Press release, Pulse Biosciences, JUL 3, 2024, View Source [SID1234644666]).

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The Company received basic subscriptions and over-subscriptions in excess of $83 million, equal to approximately 138% of the $60 million gross proceeds limit in the rights offering, and subscriptions from over 800 accounts, including those of the Company’s Executive Chairman, Robert Duggan. Available Units were allocated proportionately among those rights holders who exercised their over-subscription right based on the number of Units each rights holder subscribed for under its basic subscription rights, in accordance with the procedures described in the prospectus, as amended to date, relating to the rights offering. The remaining oversubscription amounts will be returned by Broadridge Corporate Issuer Solutions, LLC (the "Subscription Agent") to the investors.

The rights offering resulted in the sale of six million units (the "Units"), at a price of $10.00 per Unit. Each Unit consisted of one share of the Company’s common stock, par value $0.001 per share, and two warrants, each being a warrant to purchase one-half of one share of common stock. The common stock and warrants comprising the Units separated upon the closing of the rights offering and were issued individually. A total of 5,999,999 shares of common stock and warrants to acquire up to an additional approximately six million shares of common stock were issued in the offering. The Company received aggregate gross proceeds from the rights offering of $60 million. If exercised, additional gross proceeds of up to $66 million may be received through the exercise of warrants issued in the rights offering. Each warrant will be exercisable for $11.00 per whole share, which equals 110% of the subscription price for the Units. Warrants are exercisable immediately and will expire on the fifth anniversary of the closing of the rights offering. Half of the warrants issued in the rights offering are redeemable by the Company if the Company’s stock trading price exceeds $16.50 for twenty consecutive trading days and the other half of the warrants issued in the rights offering are redeemable by the Company if its stock trading price exceeds $22.00 for twenty consecutive trading days.

Investors who participated in the rights offering should expect to see the shares and warrants issued to them in book-entry, or uncertificated, form. Shares, warrants and any excess subscription payments are expected to be distributed by the Subscription Agent on or about July 5, 2024.

After giving effect to the issuance of 5,999,999 shares of common stock in the rights offering (but excluding up to approximately six million shares of common stock underlying the warrants issued in the rights offering), the Company has 61,228,332 shares of common stock issued and outstanding.

The Company plans to use proceeds from the offering principally to support further product and clinical development, future regulatory submissions and commercial readiness of its three leading CellFX nsPFA products, Percutaneous Electrode, Cardiac Clamp, and 360° Cardiac Catheter. Each device is designed to deliver significant clinical advantages compared to the current standards of care and have a potential profound positive impact on healthcare for both patients, providers and other stakeholders.

The rights offering was made pursuant to the Company’s registration statement on Form S-3, as modified by the post-effective amendment filed with the Securities and Exchange Commission ("SEC") on May 28, 2024, which was deemed effective by the SEC on May 31, 2024, including the prospectus contained therein, as further modified by the prospectus filed pursuant to Rule 424(b)(2) of the Securities Act of 1933, which contains the detailed terms of the rights offering and was filed with the SEC on June 4, 2024.

On July 2, 2024 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported it has completed the resubmission of its Biologics License Application ("BLA") to the U.S. Food and Drug Administration ("FDA") for cosibelimab, its anti-programmed death ligand-1 ("PD-L1") antibody, as a potential new treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinoma ("cSCC") who are not candidates for curative surgery or curative radiation (Press release, Checkpoint Therapeutics, JUL 2, 2024, View Source [SID1234644647]).

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The BLA resubmission follows Checkpoint recently reaching alignment with the FDA on its BLA resubmission strategy to potentially address all approvability deficiencies outlined in the complete response letter ("CRL") received last December, in which FDA only cited findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization ("CMO") as approvability issues to address in a BLA resubmission. The CRL did not state any concerns about the clinical data package, safety, or labeling for the approvability of cosibelimab.

The BLA resubmission is supported by the results of Checkpoint’s studies in selected recurrent or metastatic cancers, including pivotal cohorts in metastatic and locally advanced cSCC. Safety and efficacy results from the metastatic cSCC cohort were published in October 2023 in the Journal for ImmunoTherapy of Cancer (JITC) (doi:10.1136/jitc-2023-007637).

Additionally, in July 2023, Checkpoint announced longer-term data for cosibelimab from its pivotal studies in locally advanced and metastatic cSCC demonstrating a deepening of response over time, resulting in higher complete response rates than previously reported (55% objective response rate; 26% complete response rate in locally advanced cSCC and 50% objective response rate; 13% complete response rate in metastatic cSCC).

Cosibelimab is a potential differentiated, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to PD-L1 and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T-cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained high tumor target occupancy of PD-L1 to reactivate an antitumor immune response and the additional potential benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy.

On 2 July 2024 Ipsen reported confirmation of an expanded collaboration and license agreement with Exelixis, Inc. for the development of Cabometyx (cabozantinib) in advanced pancreatic neuroendocrine tumors (pNETs) and advanced extra-pancreatic neuroendocrine tumors (epNETs) (Press release, Ipsen, JUL 2, 2024, View Source [SID1234644631]). The agreement is based on positive outcomes from the CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology and sponsored by the National Cancer Institute (NCI), which investigated Cabometyx versus placebo in people living with advanced pNETs or advanced epNETs whose disease had progressed after prior systemic therapy. An independent Data and Safety Monitoring Board recommended to stop accrual to the study, unblind patients and allow crossover from placebo to Cabometyx. This was due to early efficacy demonstrated at an interim analysis in both of the trial’s cohorts, with clinically meaningful improvements in progression-free survival (PFS).1

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"With many people diagnosed with neuroendocrine tumors at an advanced stage of disease and treatment options limited upon progression, the need for efficacious new therapies is extensive," said Christelle Huguet, EVP and Head of Research and Development, Ipsen. "The positive results demonstrated for Cabometyx within the CABINET Phase III trial represent clinically meaningful improvements in progression-free survival at a challenging stage of disease where there are few or no available treatment options. We look forward to discussing these clinical findings with regulatory authorities."

Neuroendocrine tumors (NETs) are a group of uncommon tumors that develop in the cells of the neuroendocrine system throughout the body.2,3 The symptoms of NETs are often not distinct and difficult to identify, leading to delays in diagnosis, with 58% of people presenting with metastatic disease at diagnosis.3 The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.3,4 The survival rate varies greatly depending on the primary site and stage of disease, however for people living with advanced pNETs which has spread to distant parts of the body, the prognosis is poor, with a five-year survival rate of 23%.5

CABINET Phase III trial

Data from the study, which demonstrated PFS benefits at interim analyses, were presented at the European Society for Medical Oncology Congress 2023 by Professor Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute, Boston:1

In the pNET cohort, at a median follow-up of 16.7 months, median PFS based on local radiology review was 11.4 months for Cabometyx versus 3.0 months for placebo (hazard ratio (HR) 0.27 [95% confidence interval (CI) 0.14-0.49] p<0.0001)1
In the epNET cohort, at a median follow-up of 13.9 months, median PFS based on local radiology review was 8.3 months for Cabometyx versus 3.2 months for placebo (HR 0.45 [95% CI 0.30-0.66] p<0.0001)1
The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were

On July 2, 2024 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotech company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported that the DSMB completed its first safety assessment of the Phase 2b trial PHOEBUS, the largest one to date for a microbiome therapy in oncology, and recommended continuation of the trial without modification (Press release, MaaT Pharma, JUL 2, 2024, View Source [SID1234644651]). The trial is an international, multi-center, randomized, double-blind, testing MaaT033, an oral freeze-dried formulation against placebo, set to be conducted in up to 56 clinical investigation sites and is expected to enroll 387 patients (NCT05762211).

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The DSMB, composed of 5 independent experts, reviewed safety data on the first 20 patients (cutoff date as of April 30th, 2024) and concluded that safety was acceptable and well tolerated. Since its first clinical entry in 2020, MaaT033, a drug candidate produced by combining the microbiota from multiple donors using a patented "pooling" process, has continuously displayed a good safety profile.

"The positive outcome of this first DSMB review of the PHOEBUS study significantly builds on the favorable safety and tolerability profile exhibited by MaaT033," said Gianfranco Pittari, M.D., PhD, Chief Medical Officer of MaaT Pharma. "We are very enthusiastic about MaaT033’s potential to ensure an optimal microbiome ecosystem and enhance clinical outcomes in patients undergoing allogeneic stem cell transplantation."

"MaaT033 is designed for ambulatory use and chronic treatment; it will address a substantial market of approximately 11,000 patients annually, and with its freeze-dried capsule formulation it will significantly drive our growth," highlighted Hervé Affagard, Chief Executive Officer and co-founder of MaaT Pharma. "With the GMP manufacturing facility at full capacity, we will produce up to 1,300,000 capsules annually, meeting patient demand and supporting our innovative microbiome therapies".

On July 2, 2024 Biodexa Pharmaceuticals PLC ("Biodexa" or the "Company") (Nasdaq: BDRX), an acquisition-focused clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs, reported data from a Phase 1 study of MTX110 in Diffuse Midline Glioma ("DMG") f/k/a Diffuse Intrinsic Pontine Glioma, or DIPG, an orphan pediatric brain cancer were presented over the weekend at the 21st International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) in Philadelphia, PA (Press release, Midatech Pharma, JUL 2, 2024, View Source [SID1234644652]).

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Results of the Phase 1 study
Overall, the treatment was well tolerated by patients. There was one Grade 4 adverse event assessed by the investigators as unrelated to the drug but related to the infusion and tumor anatomy. Most other adverse events were related to infusion and were deemed Grade 2 to 3.

Although the study was not powered to reliably demonstrate efficacy, median progression free survival (PFS) was 10 months (range 8 to 20 months) and overall survival (OS) of patients in the study was 16.5 months (range 12 to 35 months). This compares favourably with median OS in a cohort of 316 cases of 10.0 months (Jansen et al, 2015. Neuro-Oncology 17(1):160-166).

Design of the Phase 1 study
The open label investigator-initiated study was conducted by Columbia University Irving Medical Center in patients newly diagnosed with DMG. Patients were administered MTX110 via convection enhanced delivery ("CED") using a subcutaneous pump connected to a catheter directly implanted into the pons in a 3+3 dose-escalating design (NCT 04264143).

As this was the first ever study of repeated infusions to the pons via an implanted CED catheter, the primary endpoint of the study was to evaluate the safety and maximum tolerated dose with secondary endpoints of Progression Free Survival and Overall Survival.

The number of infusions was limited to two, each of 48 hours, seven days apart. Nine patients were treated in the study (30 M group, n=3; 60 M group, n=4; 90 M group (optimal dose), n=2). Although the study was not powered to reliably demonstrate efficacy, median overall survival (OS) of patients in the study was 16.5 months. This compares favourably with median survival rate in a cohort of 316 cases of 10.0 months (Jansen et al, 2015. Neuro-Oncology 17(1):160-166).

MTX110 in DMG
In October 2020, the Company announced headline results from a Phase I study at the University of California, San Francisco ("UCSF") in patients with DMG (the "UCSF study" NCT03566199).

The primary endpoint of the study was to determine the dosage regimen to be used in a proposed Phase II study of the safety and efficacy of MTX110 in patients with DIPG. Preliminary high-level data from the UCSF study supports a dose of between 60µM and 90µM of MTX110, depending upon patient tolerance over the course of 12 infusions in Phase II.

In total, seven patients were recruited into the UCSF study. Patients were newly diagnosed with DMG and received focal external beam radiation therapy four to 14 weeks before commencement of MTX110 treatment. MTX110 was administered directly into the tumour via a micro-catheter using CED with gadolinium-enhanced intra-operative MRI to guide and track drug distribution to the tumour. Patients could receive up to 12 cycles of treatment every four to eight weeks. The dose was escalated between and within patients as tolerated initially by increasing the infusion volume at a concentration of 30µM MTX110 and then with higher drug concentrations of 60µM and 90µM as the sixth and seventh dose increments, respectively.

Median overall survival based on Kaplan Meier analysis was 26.06 months. Survival was not an endpoint of the UCSF study nor was the study powered for statistical significance.

About MTX110
MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables CED at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for DMG (NCT03566199, NCT04264143) and recurrent medulloblastoma (NCT04315064), and recurrent glioblastoma (NCT 05324501). MTX110 is delivered directly into and around the patient’s tumor via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumor to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DMG tumor cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DMG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).