As previously disclosed, on June 24, 2021, Prothena Corporation plc ("Prothena") reported that Bristol Myers Squibb ("BMS") exercised its option under the terms of the ongoing global neuroscience research and development collaboration (the "Master Collaboration Agreement") to enter into an exclusive U.S. license for PRX005, and, on July 30, 2021, Prothena entered into a U.S. License Agreement (the "Tau U.S. License Agreement") granting BMS the exclusive license to develop, manufacture and commercialize antibody products in the United States targeting tau ("Tau Collaboration Products") for any and all uses or purposes with respect to any human or animal disease, disorder or condition (Filing, 8-K, Prothena, JUL 10, 2023, View Source [SID1234633143]).

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On July 5, 2023 and pursuant to the option exercised by BMS under the Master Collaboration Agreement, Prothena and BMS entered into a Global License Agreement (the "Tau Global License Agreement") granting BMS the exclusive license to develop, manufacture and commercialize Tau Collaboration Products globally for any and all uses or purposes with respect to any human or animal disease, disorder or condition. The Tau Global License Agreement supersedes and replaces the Tau U.S. License Agreement in its entirety.

The Tau Global License Agreement includes an exercise fee payable to Prothena of $55 million. The Tau Global License Agreement replaces the regulatory and sales milestones under the Tau U.S. License Agreement, and increases the amounts payable under such milestones from up to $465 million to up to $562.5 million. The tiered royalties on net sales remain the same, and such exercise fees, milestones and royalty payments are subject to certain reductions as specified in the Tau Global License Agreement. In addition, Prothena will be eligible to receive reimbursement of certain chemistry, manufacturing and control (CMC) related expenses incurred by Prothena under the Master Collaboration Agreement, not to exceed $15 million.

Under the Tau Global License Agreement, BMS will continue to pay royalties on a product-by-product and country-by-country basis, until the latest of (i) expiration of certain patents covering the Tau Collaboration Products in such country of sale, (ii) expiration of any applicable regulatory exclusivity in such country of sale, and (iii) an agreed period of time after the first commercial sale of the Tau Collaboration Products in such country of sale (the "Royalty Term").

The term of the Tau Global License Agreement will continue on a product-by-product and country-by-country basis until the expiration of all Royalty Terms with respect to all Tau Collaboration Products. Either party is entitled to terminate the Tau Global License Agreement for material breach, bankruptcy or safety reasons. Prothena is entitled to terminate the Tau Global License Agreement for a failure by BMS to exercise due diligence with respect to its global rights for the Tau Collaboration Products under the Master Collaboration Agreement, and for certain patent challenges by BMS. The Tau Global License Agreement imposes certain post-termination rights and obligations on the parties, which vary based on the reasons giving rise to the termination.

The foregoing description of the Tau Global License Agreement is not a complete description thereof, and is qualified in its entirety by reference to the actual agreement that will be filed with the Securities and Exchange Commission (the "SEC") as an exhibit to Prothena’s Quarterly Report on Form 10-Q for the quarter ending September 30, 2023.

The foregoing descriptions of (i) the Master Collaboration Agreement and (ii) the Tau U.S. License Agreement are not complete descriptions thereof, and are qualified in their entirety by reference to the actual agreements that are filed with the SEC as Exhibits 10.8 and 10.10, respectively, to Prothena’s Annual Report on Form 10-K filed February 28, 2023.

On July 10, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that the independent Data Safety Monitoring Board (DSMB) of the Phase III ASPIRE clinical trial for patients with untreated metastatic pancreatic ductal adenocarcinoma has completed its pre-specified review of safety data for treated patients in the trial (Press release, Panbela Therapeutics, JUL 10, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-preliminary-safety-analysis-for-aspire-trial [SID1234633142]). The DSMB has recommended that the study continue without modification. The ASPIRE Trial is a global randomized, double-blind placebo-controlled clinical trial to evaluate ivospemin in combination with gemcitabine and nab-Paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma. "We are pleased that no safety concerns were identified and the DSMB’s recommendation is to proceed without modification to the ASPIRE Trial. With a focus on enrollment and completing site initiations, we are looking forward to the interim analysis in early 2024." said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela.

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About Panbela’s Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of anticipated catalysts with programs ranging from pre-clinical to registration studies.

Ivospemin (SBP-101)

Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial.

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increasing polyamine export and catabolism. In a Phase III clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase III trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose powder sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigatorinitiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.

On July 10, 2023 NanoString Technologies, Inc. (NASDAQ:NSTG), a leading provider of life science tools for discovery and translational research, reported preliminary financial and operational highlights for the second quarter ended June 30, 2023 (Press release, NanoString Technologies, JUL 10, 2023, View Source [SID1234633141]).

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"We are excited to report that our teams delivered strong preliminary revenue results for the second quarter, with preliminary results exceeding consensus estimates and the upper end of our guidance ranges," said Brad Gray, President and CEO of NanoString. "Customers are focused on the potential for spatial analysis to advance science, and value the RNA-plex and protein capabilities our spatial platforms provide. During Q2, a competitor launched a campaign using a ruling in the Munich regional court to try to frighten customers to cancel orders for our CosMx Spatial Molecular Imager, even though the preliminary ruling was limited to Germany. Despite this challenge, through the strength of our technology and the hard work of our team, we fulfilled or retained approximately 97% of our cumulative CosMx instrument orders and captured orders for new CosMx instruments at a faster pace than in Q1."

Preliminary Second Quarter Financial Results

•Revenue is expected to be over $44 million, representing year on year growth of approximately 37%, above the upper end of our guidance range of $40 to $42 million and the consensus revenue estimate of $41 million
•Spatial biology revenue is expected to be over $23 million, at approximately the midpoint of our guidance range of $23 to $24 million, and in line with the consensus revenue estimate of $23 million
•nCounter revenue, inclusive of all service and other revenue, is expected to be approximately $21 million, above the upper end of our guidance range of $17 to $18 million and the consensus revenue estimate of $18 million
Second Quarter Highlights
Spatial Biology
•Accelerated CosMx shipments during Q2, resulting in Q2 spatial biology instrument revenue growth of approximately 188% year-over-year
•Successfully defended substantial CosMx instrument order book, fulfilling or retaining approximately 97% of cumulative orders as of June 30, 2023
•Captured new orders for spatial biology instruments at a rate exceeding the Q1 pace, and retained more than $30 million in CosMx instrument order backlog as of June 30, 2023
•Recorded spatial biology consumables revenue growth of approximately 44% year-over-year, and approximately $85,000 of annualized pull-through, driven by a steady GeoMx consumable pull-through over a larger installed base supplemented by growing shipments of CosMx consumables

nCounter

•Recorded nCounter consumables revenue growth of approximately 8% year-over-year and approximately $46,000 of annualized pull-through
These preliminary results are based on management’s initial analysis of operations for the quarter ended June 30, 2023 and are subject to further internal review and review by the company’s external auditors.
Guidance
Management reiterated its full year revenue guidance of $175-185 million, representing annual revenue growth of 41% at the midpoint of the guidance range.

Second Quarter Conference Call

The Company plans to release full operating results for the second quarter of 2023 after the close of trading on Thursday, August 3, 2023. Company management will host a conference call beginning at 4:30pm ET to discuss those results and provide updated financial guidance.

Investors and other interested parties should register for the conference call in advance by visiting View Source Following registration, an email confirmation will be sent that includes dial-in details and unique conference call codes for entry. Registration is open throughout the call but to ensure connection for the full call, registration in advance is recommended.

The link to the webcast and audio replay will be made available at the Investor Relations website: nanostring.com.
A replay of the call will be available beginning August 3, 2023, at 7:30pm ET through midnight on August 17, 2023. To access the replay, dial (800) 770-2030 or (647) 362-9199 and reference Conference ID: 72369. The webcast will also be available on the Company’s website for one year following the completion of the call.

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).