On June 16, 2020 Monopar Therapeutics Inc. (Nasdaq: MNPR) and NorthStar Medical Radioisotopes, LLC reported a 50/50 collaboration to develop potential Radio-Immuno-Therapeutics (RITs) to treat severe COVID-19 (patients with SARS-CoV-2 infection) (Press release, Monopar Therapeutics, JUN 16, 2020, View Source [SID1234611968]). Monopar is a clinical-stage biopharmaceutical company and NorthStar is a commercial producer and supplier of medical radioisotopes. This collaboration combines NorthStar’s expertise in the innovative production, supply, and distribution of important medical radioisotopes with Monopar’s expertise in therapeutic drug development and its pre-IND stage humanized urokinase plasminogen activator receptor (uPAR) targeted monoclonal antibody known as MNPR-101, along with a proprietary portfolio of related monoclonal antibodies that target uPAR or its ligand uPA.

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The uPA system (comprised of the serine protease enzyme uPA and its receptor uPAR) has been demonstrated to be selectively expressed on aberrantly activated immune cells. In response to coronavirus infection, these rogue immune cells produce pro-inflammatory cytokines that can cause runaway inflammation throughout the body, commonly referred to as a cytokine storm. It is this systemic hyper-inflammatory state that is thought to be largely responsible for the severe lung injury and further multiple organ damage that contributes to poor outcomes and death in patients with severe COVID-19.

In this collaboration, Monopar and NorthStar plan to couple MNPR-101 to a therapeutic radioisotope supplied by NorthStar in order to create a highly selective agent that has the potential to kill aberrantly activated cytokine-producing immune cells. By eradicating these cells with a targeted RIT, the goal is to spare healthy cells while quickly reducing the cytokine storm and its harmful systemic effects.

"This collaboration is a powerful combination of unique scientific and technical expertise to help combat severe COVID-19," said Chandler Robinson, MD, CEO of Monopar Therapeutics. "The companies will be conducting a development program to determine if Monopar’s uPA/uPAR monoclonal antibodies can be transformed into RITs that are effective as treatments against severe COVID-19, as well as other corona viruses."

"We are pleased to work together with Monopar in the battle against COVID-19," said Stephen Merrick, CEO of NorthStar Medical Radioisotopes." Our hope is that, by joining forces, we can develop a targeted radiopharmaceutical treatment that has the ability to prevent patients with severe COVID-19 from being placed on ventilators and from dying."

"To help mitigate the cytokine storm and reduce deaths associated with COVID-19, our goal is to develop an RIT that selectively eliminates the rogue aberrantly activated immune cells that produce these cytokines," said Andrew Mazar, PhD, Chief Scientific Officer of Monopar. "uPAR is selectively expressed on these rogue immune cells but not on healthy cells. An antibody carrying a therapeutic radioisotope could gain entry into these cells through uPAR and deliver its cytotoxic payload to kill these cells while sparing normal tissue."

"NorthStar will apply its expertise to identify and supply the optimal therapeutic radioisotope to couple with Monopar’s uPAR monoclonal antibodies," said James T. Harvey, PhD, Senior Vice President and Chief Science Officer of NorthStar. "We will deploy the most appropriate development approaches and production technology to ensure that both development and, if successful, commercial-scale volumes of this radioisotope can be supplied in order to meet potential demand."

This targeted therapeutic approach to treating severe COVID-19 is supported by a recently published study (Rovina et al. 2020) demonstrating that soluble urokinase plasminogen activator receptor (suPAR), which is shed by aberrantly activated immune cells that make uPAR, is an early predictor of severe respiratory failure in COVID-19 and its presence increases as patients develop severe COVID-19.

On June 16, 2020 Blue Earth Diagnostics, a Bracco company focused on molecular imaging diagnostics, and PETNET Solutions Inc., a Siemens Healthineers company specializing in the manufacturing and distribution of positron emission tomography (PET) radiopharmaceuticals, reported the signing of a commercial manufacturing and distribution agreement (Press release, Blue Earth Diagnostics, JUN 16, 2020, View Source [SID1234561131]). Under the new multi-year agreement, PETNET will expand production and continue distribution of Axumin as well as commercially manufacture and distribute Blue Earth Diagnostics’ investigational radiohybrid Prostate-Specific Membrane Antigen-targeted agent, rhPSMA-7.3 (18F), pending its successful development and potential FDA approval. PETNET is currently a supplier of rhPSMA-7.3 (18F) for Blue Earth Diagnostics’ Phase 3 rhPSMA-7.3 (18F) clinical trials in newly diagnosed and recurrent prostate cancer (LIGHTHOUSE NCT04186819 and SPOTLIGHT NCT04186845, respectively). Axumin is a novel molecular imaging agent indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men who have elevated blood levels of prostate specific antigen (PSA) following prior treatment.

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"We are pleased to work in conjunction with PETNET Solutions, the leading supplier of PET radiopharmaceuticals in the United States, to continue to expand Axumin production and distribution in the United States," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "Axumin launched as the first FDA-approved 18F imaging agent for recurrent prostate cancer in 2016, and is now available at more than 1,100 imaging centers across the United States. Based on Blue Earth Diagnostics’ success in using its extensive radiopharmacy network for U.S. Axumin production and distribution, we chose PETNET as a clinical trial manufacturer of rhPSMA-7.3 (18F) for our Phase 3 clinical trials. Under this new agreement, PETNET will also provide commercial production and distribution of rhPSMA-7.3 (18F) pending its successful development and potential FDA approval. We believe that the complementary mechanisms of action of Axumin and rhPSMA-7.3 (18F) may ultimately allow physicians and their patients flexibility in selecting the diagnostic agent most appropriate to each specific clinical situation. The new agreement expands Axumin production in 2021, so that physicians and patients may have more convenient access to the product."

"We are proud to continue working with Blue Earth Diagnostics as the U.S. commercial supplier in making Axumin available to imaging centers and their patients, and we are pleased that PETNET Solutions has been selected to manufacture and distribute rhPSMA-7.3 (18F)," said Barry Scott, Head of PETNET Solutions Inc. "PETNET’s broad national network of radiopharmacies enables us to increase access to 18F PET radiopharmaceuticals to help healthcare providers address society’s most challenging diseases."

About Axumin (fluciclovine F 18)

Axumin (fluciclovine F 18) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues and is labeled with the radioisotope F 18 for PET imaging. Fluciclovine F 18 was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin was approved by the U.S. Food and Drug Administration in May 2016, following Priority Review, and is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications including neuro-oncology.

About rhPSMA

rhPSMA-7.3 (18F) is an investigational imaging agent that consists of a radiohybrid Prostate-Specific Membrane Antigen (PSMA)-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and is labeled with the 18F radioisotope for PET imaging. rhPSMA compounds can also be labeled with radioisotopes such as 177Lu and 225Ac for therapeutic use. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA imaging technology from Scintomics in 2018, with an option to therapeutic rights. rhPSMA originated from the Technical University of Munich, Germany, and has been utilized clinically under German legislation at the Department of Nuclear Medicine there for the diagnostic imaging of men with both primary and recurrent prostate cancer. rhPSMA compounds have not received regulatory approval.

NOTE: Axumin (fluciclovine F 18) injection is FDA-approved for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States and Europe. Please be aware that the approval status and product label for Axumin varies by country worldwide. For EU Axumin product information refer to: View Source;mid=WC0b01ac058001d124.

U.S. Indication and Important Safety Information about Axumin

INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

On June 16, 2020 C4 Therapeutics, Inc. (C4T), a biotechnology company pioneering a new class of small-molecule drugs that selectively destroy disease-causing proteins via degradation, reported the closing of a $170 million financing, including $150 million in Series B equity co-led by existing investor Cobro Ventures and new investor Perceptive Advisors and $20 million in venture debt by Perceptive Advisors (Press release, C4 Therapeutics, JUN 16, 2020, View Source [SID1234561147]). Additional new equity investors in the round included Adage Capital Management, Axil Capital, Bain Capital Life Sciences, Commodore Capital, 3E Bioventures Capital, HBM Healthcare Investments, Lightchain Capital, Logos Capital, Mizuho Securities Principal Investment, Nextech, RA Capital Management, RTW Investments, Sphera Funds Management, Taiwania Capital Management, Yonjin Venture, and funds and accounts managed by T. Rowe Price Associates, Inc and Janus Henderson Investors. Existing investors also participated.

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C4T will use the proceeds to advance multiple degrader drug candidates to human proof-of-concept and to expand the Company’s capabilities. C4T has invested significantly in its TORPEDO platform, which combines a robust chemistry engine, proprietary assays, and high throughput screening with predictive modeling for accelerated, informed, and efficient discovery and design of high-quality drug candidates.

"This funding comes at a significant juncture, as our company is moving to a clinical stage. We plan on filing our first IND by the end of this year and expect to have four drug candidates in the clinic by the end of 2022. We have a deep pipeline addressing a diverse set of oncology indications that provides us with significant optionality. Protein degraders allow for more potent and durable pharmacologic responses than traditional inhibitors, and we bring a differentiated approach to this transformative modality through our proprietary TORPEDO platform," said Marc Cohen, Co-Founder, Chairman and CEO of C4 Therapeutics. "We look forward to advancing our programs with the goal of bringing new therapeutics to patients suffering from life-threatening diseases and are thrilled to have attracted top-tier life science investors to our company in this very oversubscribed round."

"C4 Therapeutics is a pioneer in this exciting and promising new protein degradation space," said Adam Stone, Chief Investment Officer of Perceptive Advisors and co-lead of this financing. "With their strong science and world class team we have no doubt that they will be able to bring powerful new therapeutics to patients and we are excited to collaborate with C4T on this important mission."

"C4T remains at the forefront of this novel modality with its proprietary platform validated by high-value strategic partnerships," added Todd Kaloudis, Managing Director at Cobro Ventures, co-lead of this round. "We are proud to support C4T in its mission to destroy disease-causing proteins and deliver breakthrough treatments for significant unmet medical needs."

Jefferies and Locust Walk served as transaction advisors to the Company in the Series B financing.

On June 16, 2020 Sanofi reported to increase its vaccines research and production capabilities (Press release, BioSpace, JUN 16, 2020, View Source [SID1234561165]). As part of the plan it will invest $679.4 million (€610 million) to create a new production site and a research center, both in France, both dedicated to vaccines.

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"Sanofi’s heart beats in France," said Sanofi’s chief executive officer Paul Hudson in a statement. "We have a long history and exceptional teams working throughout the country, embodying our strong values. By investing in a new industrial site and a R&D center, Sanofi positions France at the core of its strategy, aiming to make France a world-class center of excellence in vaccine research and production."

The company’s Evolutive Vaccine Facility (EVF) will be based in Neuville sur Saone. This industrial site will leverage the latest innovative vaccine production technologies. The company will invest €490 million over a five-year period, with plans to create 200 new jobs.

Sanofi Pasteur is Sanofi’s vaccine company and it will utilize the manufacturing site to handle any new pandemics. Sanofi indicates that EVF "is a new type of factory designed around a central unit housing several fully digital production modules that make it possible to produce three to four vaccines simultaneously, versus only one in current industrial sites. This modularity will make it possible to prioritize the production of a specific vaccine in a more timely manner based on public health issues."

Of the total funding, €120 million will go to form a new R&D center at the Sanofi Pasteur site in Marcy-l’Etoile to develop future vaccines. It too will be a state-of-the-art digital facility with specialized laboratories. Sanofi indicates it plans for the facility to become a world reference for preclinical research and pharmaceutical and clinical development.

Hudson added, "Sanofi is a major healthcare player in France, in Europe, and worldwide. It is our responsibility to focus our resources and expertise against the current pandemic, but also to invest in preparing for future ones. We welcome the ongoing collaboration and commitment of the French authorities who we have been working alongside with the last several months to achieve this."

Sanofi, in collaboration with GlaxoSmithKline, is approaching the development of two different COVID-19 vaccines with two different technological approaches. The first, with GSK, is using recombinant DNA technology, which would allow for manufacturing very large quantities of antigens, the proteins that are injected to stimulate the immune system. The second is messenger RNA technology in collaboration with TranslateBio. This is a new technology also being utilized by U.S.-based Moderna and Germany-based BioNTech, which is collaborating with Pfizer.

Sanofi says it is committed to making its vaccine accessible to "all and around the world."

On April 14, Sanofi and GSK signed a letter of intent to collaborate on the COVID-19 vaccine using technology from both companies. Sanofi is contributing its S-protein COVID-19 antigen, which utilizes recombinant DNA technology. This allows for an exact genetic match to proteins found on the virus surface. The DNA sequence that codes for the antigen has been combined into the DNA of the baculovirus expression program, which Sanofi uses for its recombinant influenza product in the U.S.

GSK is contributing its pandemic adjuvant technology, which can decrease the amount of vaccine protein required per dose, which allows for more manufacturing volume.

At the time, Emma Walmsley, chief executive officer of GSK, said, "This collaboration brings two of the world’s largest vaccines companies together. By combining our science and our technologies, we believe we can help accelerate the global effort to develop a vaccine to protect as many people as possible from COVID-19."

The deal with TranslateBio was signed earlier, on March 27. That deal leverages an existing agreement from 2018 to develop mRNA vaccines for infectious diseases. The primary aspect of that agreement is TranslateBio is producing multiple mRNA constructs using its technology platform to discover, design, and manufacture several SARS-CoV-2 vaccine candidates. Sanofi will provide its vaccine expertise and its external research network to advance vaccine candidates.

On June 16, 2020 Midatech Pharma PLC (AIM: MTPH.L; Nasdaq: MTP), a drug delivery technology company focused on improving the bio-delivery and bio-distribution of medicines reported its audited preliminary results for the year ended 31 December 2019 (Press release, Midatech Pharma, JUN 16, 2020, View Source [SID1234562738]).

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Financial highlights

·Total gross revenue(1) for the year of £0.7m (2018: £1.9m, 2017: £1.0m).

·Statutory revenue(2) for 2019 of £0.3m (2018: £0.1m, 2017: £0.1m).

·Subscription, Placing and Open Offer in February 2019 raised £12.3m (net) and Registered Direct Offering in the US in October 2019 raised $2.5m (£1.8m) (net).

·Receipt of €3.6m (£3.1m) (net) non-dilutive Reindus loan and award of Guazatu loan of €1.5m.

·Provisional award of a GlioKIDS grant of €2.7m (£2.3m), subject to confirmation of Midatech’s status as an SME, to support a Phase II trial of MTX110.

·Cash and deposits at 31 December 2019 of £10.9m (2018: £2.3m, 2017: £13.2m).

·Net loss from continuing operations of £9.1m (2018: £10.4m loss, 2017: £11.7m loss) with net cash inflow in the year of £8.4m (2018: £10.9m outflow, 2017: £4.1m outflow).

·Tax credit receivable of £1.8m (2018: £1.9m, 2017: £1.2m).

1)Total gross revenue represents collaboration income from continuing operations plus grant revenue.

2Statutory Revenue represents total gross revenue, excluding grant revenue.

Operational highlights

·First substantive licensing agreement with China Medical System Holdings Ltd ("CMS") for the Group’s pipeline products for Greater China accompanied by an £8.0m strategic investment in the Company, as part of a Subscription, Placing and Open Offer executed in February 2019.

·MTX110 received orphan drug designation for malignant glioma including DIPG from the FDA.

Post period end highlights

·In January 2020, a study of subcutaneous administration of MTD201 compared with traditional intramuscular administration in healthy volunteers showed similar pharmacokinetics and bioavailability, offering the potential for a differentiated, more patient-friendly product profile.

·In March 2020, an exploratory study was initiated by Columbia University in five patients with DIPG using an alternative convection enhanced delivery system.

·Also in March 2020, following a General Meeting, the Company’s ordinary shares of £0.00005 each were consolidated on a one-for-20 basis into ordinary shares of £0.001 each. At the same meeting a resolution was passed to change the ratio of the Company’s American Depositary Receipts ("ADRs"). This will change from one ADR representing 20 Existing Ordinary Shares to one ADR representing five new ordinary shares.

·On 31 March 2020, the Company announced a wide-ranging strategic review including termination of MTD201, closure of the Company’s Bilbao operations and a re-alignment of the Board.

·On 20 April 2020, the Company announced an update to the strategic review including the appointment of an adviser and start of a ‘formal sale process’ under the Takeover Code.

·On 18 May 2020, the Company announced that it had raised gross proceeds of £4.3m (£3.8m net of expenses) in a combined UK Placing and Registered Direct Offering in the US. The combined offerings resulted in the issuance of 15.8 million new Ordinary Shares and 16.5 million new Warrants.

·On 8 June 2020, the Company received a letter sent on behalf of Secura Bio, Inc. ("Secura Bio"), dated 1 June 2020, purporting to terminate a License Agreement, dated 5 June 2017 (the "Secura License Agreement"), by and between Midatech Limited and Novartis AG, which Novartis AG subsequently transferred to Secura Bio. Pursuant to the Secura License Agreement, Midatech Limited was granted a non-exclusive worldwide, sublicenseable license to certain patents of panobinostat, the active pharmaceutical ingredient of the Company’s development product MTX110. Midatech Limited’s rights are limited to the treatment of brain cancer in humans, administered by convection-enhanced delivery. The Company plans to continue to pursue development of MTX110 and the strategic review process previously disclosed. The Company is also reviewing with its outside counsel remedies it may have if Secura Bio does not withdraw the notice and otherwise cease to interfere with its ongoing business and strategic review process, which the Company has formally requested. The Company is evaluating available actions to protect its rights under the Secura License Agreement and its assets.

Stephen Stamp, CEO and CFO commented "This has been an extremely difficult period for Midatech with the termination of in-house development of our lead programme, closure of our Bilbao operations and the loss of 47 jobs, over two-thirds of our employees. I should like to recognise the professionalism of the team in making these difficult decisions and the grace with which they have been accepted. Our focus now is to evaluate all available options for extracting maximum value from Midatech’s platform technologies."