On July 10, 2023 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported a global licensing, co-development, and commercialization agreement with Janssen Pharmaceutica NV ("Janssen"), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, for the investigational, potential first-in-class radioenhancer NBTXR3 (Press release, Nanobiotix, JUL 10, 2023, View Source [SID1234633140]).

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NBTXR3 is currently being evaluated in several studies across solid tumor indications including NANORAY-312, a global Phase 3 pivotal study evaluating NBTXR3 for the treatment of patients with locally advanced head and neck cancer. NBTXR3 is also being evaluated for its potential as a systemic agent in combination with anti-PD-1 immune checkpoint inhibitors for patients with metastatic cancers.

Under the terms of the license agreement, in collaboration with the Interventional Oncology R&D Unit at Johnson & Johnson, Nanobiotix will grant Janssen a worldwide license for the development and commercialization of NBTXR3. The license is exclusive, excepting territories previously licensed to Nanobiotix partner LianBio. Dial-in information for a conference call Nanobiotix will host to discuss the agreement can be found below.

"As pioneers in the field of nanotherapeutics for the past 20 years, we knew that the true impact of our innovation in oncology would be in its potential to reach millions of patients around the world. For that, we needed to find the right partner, at the right time, with proven global development and commercialization capabilities," said Laurent Levy, Nanobiotix chairman of the executive board. "We are delighted to collaborate with Janssen as we aim to improve the lives of patients with cancer around the world."

Nanobiotix will receive near term cash and operational support valued up to $60 million. This includes an upfront cash licensing fee of $30 million, and in-kind regulatory and development support for study NANORAY-312 valued at up to $30 million that Janssen may provide at its sole discretion. Nanobiotix will maintain operational control of NANORAY-312 and all other currently ongoing studies, along with NBTXR3 manufacture, clinical supply, and initial commercial supply. Janssen will be fully responsible for an initial Phase 2 study evaluating NBTXR3 for patients with stage three lung cancer and will have the right to assume control of studies currently led by Nanobiotix.

Nanobiotix is eligible for success-based payments of up to $1.8 billion, in the aggregate, relating to potential development, regulatory, and sales milestones. Moreover, the agreement includes a framework for additional success-based potential development and regulatory milestone payments of up to $650 million, in the aggregate, for five new indications that may be developed by Janssen at its sole discretion; and of up to $220 million, in the aggregate, per indication that may be developed by Nanobiotix in alignment with Janssen.

Following commercialization, Nanobiotix will also receive tiered double-digit royalties on net sales of NBTXR3.

"We expect this agreement, and the collaboration it enables, to further drive the expansion of NBTXR3 development and accelerate the realization of its promise for patients in need," said Bart van Rhijn, Nanobiotix chief financial officer. "We look forward to maximizing the value of NBTXR3 for our global stakeholders."

Separately, Nanobiotix is eligible to receive up to $30 million in equity investments from Johnson & Johnson Innovation – JJDC, Inc. ("JJDC") including, as part of capital increases without preferential subscription rights: (1) an initial tranche equal to the lower of 5% of the Company and $5 million; and (2) a second tranche of $25 million subject to certain maximum ownership caps in connection with a future financing.

The price of the initial tranche will be equal to $5.21 per American Depositary Share ("ADS") if that price (1) is approved by Nanobiotix shareholders or (2) exceeds 85% of the volume-weighted average price ("VWAP") of Nanobiotix ordinary shares on Euronext: Paris for three consecutive trading days, starting with the fourth trading day after the date of agreement, in each case if occurring within the ninety trading days following the date f the agreement. Also, JJDC may elect any time during that ninety-trading day period to instead consummate the initial tranche at a price per ADS equal to 85% of the VWAP of Nanobiotix ordinary shares on Euronext for three consecutive trading days starting with the fourth trading day after the date of the agreement. The second, $25 million tranche is conditioned upon, and at the same price as, a concurrent Nanobiotix financing with gross proceeds of at least $25 million (excluding the potential investment by JJDC) occurring prior to certain long-term development milestones or December 31, 2027, at the latest.

For illustrative purposes only1, in the event that the initial tranche is implemented at $5.21 per ADS, the dilutive impact for shareholders resulting from this capital increase would be 0.97% and JJDC group would own 2.65% of the Company’s share capital.

The transaction is subject to customary closing conditions and regulatory clearances including clearance by US antitrust authorities under the Hart-Scott-Rodino Act, and will become effective as soon as these conditions have been met.

As of the date the license agreement becomes effective, prior to utilizing the second tranche of equity investment outlined above and excluding near term development milestones, Nanobiotix expects to extend its cash runway into the first quarter of 2024.

The above statements are subject to the assumptions and risks described in the Cautionary Statement section of this press release below.

Conference Call and Webcast

Nanobiotix will host a conference call and live audio webcast on Monday, July 10, 2023, at 8:30 AM EDT / 2:30 PM CEST, prior to the open of the U.S. market. During the call, Laurent Levy, chief executive officer, and Bart van Rhijn, chief financial officer, will review the agreement and its potential impact on the Company.

On July 10, 2023 Biodexa Ltd (a wholly owned subsidiary of Biodexa Pharmaceuticals PLC, Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain, is pleased to announce completion of enrolment and treatment of nine paediatric patients into the ongoing investigator-sponsored Phase I study of MTX-110 in newly diagnosed DMGs (NCT 04264143).

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All of the patients (age range 4-17 years) were enrolled at the Columbia University Irving Medical Centre and received radiation therapy as per the institution’s standard of care. Each patient subsequently underwent surgery with implantation of an intratumoral catheter and a programmable subcutaneous pump and 8 out of 9 have received two infusions of MTX110 via convection-enhanced delivery (CED) separated by a period of 1 week. Concentrations of 30, 60 or 90 µM were delivered with no intra-patient dose escalation.

No dose limiting toxicities related to the study drug have been reported in the study.

Full study results are expected to be made public around the 1st quarter of 2024.

Commenting, Dr Luca Szalontay, MD, Assistant Professor of Paediatrics, Columbia University Irving Medical Centre, said: "We are looking forward to completing and reporting data from this very important safety study of MTX110 that has previously demonstrated efficacy in treatment of patients with DMG. This horrible disease is a very high unmet medical need as there was no effective treatment established for patients with DMG and survival remains very poor, at an average of 9-11 months ."

About DMG

DMG is a primary brain tumour arising in the midline structures of the brain including the pons of the brain stem, is diffusely infiltrating and cannot be surgically removed. Occurring mostly in children, the median survival rate in a cohort of 316 cases was 10.0 months and overall survival at 12 months was 35% (Jansen et al, 2015. Neuro-Oncology 17(1):160-166). Although radiotherapy prolongs survival, the majority of patients die within one year following diagnosis. Systemic chemotherapy is ineffective, often due to an inability of agents to cross the blood-brain barrier. Approximately 1,100 (data on file) individuals are diagnosed with DIPG worldwide each year.

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 therapeutic 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 recurrent glioblastoma (NCT05324501), paediatric DMG (NCT04264143) and recurrent medulloblastoma (NCT04315064). MTX110 is delivered directly into and around the patient’s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour 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 DIPG and GBM tumour 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 DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).

On July 10, 2023 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that zedenoleucel, its multi-tumor-associated antigen (multiTAA)-specific T cell product candidate, MT-401, was granted Orphan Drug Designation by the Committee for Orphan Medicinal Products of the European Medicines Agency (EMA) for the treatment of patients with acute myeloid leukemia (AML) (Press release, Marker Therapeutics, JUL 10, 2023, View Source [SID1234633137]).

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AML is a life-threatening and chronically debilitating disease that is rapidly progressive and fatal if untreated. Relapse rates after initial treatment are high, and the next step for eligible patients is an allogeneic hematopoietic stem cell transplant (HSCT). Unfortunately, AML relapse after HSCT is frequent and outcomes are dismal. Patients who relapse after HSCT have an estimated median survival of less than one year (Estey and Döhner, Lancet, 2006), highlighting the urgent need for new therapies.

MT-401 utilizes a novel non-genetically modified approach that recognizes multiple antigens expressed on tumor cells, thereby designed to minimize tumor escape. MT-401 is currently being studied in a Phase 2 clinical trial for the treatment of relapsed AML following allogeneic HSCT, and was designed to specifically target four different antigens that are upregulated in AML but have limited expression on normal cells.

In the European Union, orphan drug designation is granted to drugs intended for the treatment of life-threatening or chronically debilitating conditions affecting no more than five in 10,000 individuals in the European Union. Orphan drug designation by the EMA provides crucial support to expedite the development and market readiness of necessary drugs for such rare diseases. This designation will help Marker Therapeutics continue to develop MT-401 to fill a significant void in the treatment of AML and provides Marker Therapeutics with a range of potential benefits, including ten years of market exclusivity following approval, reduced regulatory fees, and invaluable scientific advice from the EMA during the drug development phase.

"The orphan drug designation for MT-401 by the EMA is a significant regulatory milestone," said Nadia Agopyan, Ph.D., RAC, Senior Vice President, Regulatory Affairs of Marker Therapeutics. "It acknowledges not just the potential therapeutic impact of MT-401, but also the urgent need to deliver innovative treatment options to patients living with AML. In 2020, MT-401 was also granted orphan designation by the U.S. Food and Drug Administration for the treatment of patients with AML. We are deeply committed to working with regulatory authorities to expedite the drug development and approval process."

"We are extremely proud to have been granted Orphan Drug Designation by the EMA for MT-401," said Juan F. Vera, M.D., President and Chief Executive Officer of Marker Therapeutics. "In our Phase 2 clinical trial of patients with post-transplant AML, we have observed promising results from patients with measurable residual disease, suggesting that the unique and differentiated targeting technology of MT-401 can be a potential treatment for patients with AML before relapse."

"This is an important milestone for Marker and a significant step forward in our mission to improve the lives of patients with AML, especially of those with relapsed AML where no therapeutic options have been approved. Our team at Marker is committed to accelerating the development of MT-401 and believes that this designation brings us one step closer to offering a new, potentially life-altering therapy for relapsed AML patients after stem cell transplant," concluded Dr. Vera.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 180 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated and demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect. Unlike other cell therapies which require hospitalization and close monitoring, multiTAA-specific T cells are designed to be administered in an outpatient setting.

On July 10, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported positive regulatory and clinical updates related to its registrational single-arm Phase 2 IOV-LUN-202 trial in post-anti-PD-1 NSCLC (Press release, Iovance Biotherapeutics, JUL 10, 2023, View Source [SID1234633135]).

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NSCLC Regulatory and Clinical Update:

At a Type B Pre-Phase 3 meeting held between Iovance and the U.S. Food and Drug Administration (FDA), the FDA provided positive regulatory feedback that the design of the IOV-LUN-202 trial may be acceptable for accelerated approval of LN-145 TIL therapy for patients who have progressed on or after chemotherapy and anti-PD-1 therapy for advanced (unresectable or metastatic) NSCLC without EGFR, ROS or ALK genomic mutations and had received at least one line of an FDA-approved targeted therapy if indicated by other actionable tumor mutations. Based on this FDA feedback, Iovance completed a preliminary analysis of the IOV-LUN-202 trial. This recent data cut1 included 23 NSCLC patients treated with LN-145. An ORR of 26.1% by RECIST v1.1 (n=6, one complete response and five partial responses) was observed, with a disease control rate of 82.6%. While still early on study, the median duration of response (DOR) was not reached. The DOR ranged from 1.4+ months to 9.7+ months. Treatment-emergent adverse events were consistent with the underlying disease and known adverse event profiles of non-myeloablative lymphodepletion and interleukin-2. Based on the regulatory discussions, Iovance plans to enroll a total of approximately 120 patients into the registrational IOV-LUN-202 trial. Enrollment is expected to be complete during the second half of 2024. As previously announced, Iovance is also preparing to meet with the FDA this year to discuss a randomized confirmatory trial of LN-145 in frontline advanced NSCLC patients. This confirmatory trial in frontline advanced NSCLC is expected to be well underway at the time of a potential approval in advanced post-anti-PD-1 NSCLC.

Lifileucel BLA Submission on Track in Advanced Melanoma:
The FDA’s Priority Review of Iovance’s Biologics License Application (BLA) for lifileucel in advanced melanoma remains on track and continues to progress well. The Prescription Drug User Fee Act target action date for the BLA is November 25, 2023.

Data cut date of July 6, 2023.

On July 10, 2023 Intensity Therapeutics, Inc. ("Intensity" or the "Company") (Nasdaq: INTS), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that the underwriters of its previously announced initial public offering have fully exercised their option to purchase an additional 585,000 shares of its common public stock at the IPO offering price of $5.00 per share, less underwriting discounts and commissions (Press release, Intensity Therapeutics, JUL 10, 2023, View Source [SID1234633134]).

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The total net proceeds to Intensity from the offering, including proceeds from the exercise of the underwriter’s over-allotment option, after deducting the underwriting discounts, commissions and transaction expenses, were approximately $18.9 million.

The Benchmark Company and Freedom Capital Markets acted as the joint book-running managers for the offering.

The securities described above were offered by the Company pursuant to a registration statement on Form S-1 (Registration No. 333-260565) that was previously filed with the U.S. Securities and Exchange (the "SEC") and declared effective on June 29, 2023. This offering was made only by means of a prospectus forming part of the effective registration statement. Copies of the final prospectus can be obtained through the SEC’s website at www.sec.gov or from: The Benchmark Company, LLC, Attention: Prospectus Department, 150 E. 58th Street, 17th floor, New York, NY 10155 at 212-312-6700 or by email at [email protected] and Freedom Capital Markets, 40 Wall Street, 58th Floor, New York, NY 10005, via email at [email protected] and via telephone at (800) 786-1469.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful.