On May 6, 2020 Noxopharm, a clinical-stage Australian oncology drug development company, reported that it has announced the details of the radiographic review of its DARRT-1 clinical study and is pleased to report a 27% incidence of abscopal response in soft tissue lesions using a combination of Veyonda and low-dose radiotherapy (Press release, Noxopharm, MAY 6, 2020, View Source [SID1234557158]).

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An abscopal response, a highly prized clinical response, involves radiation directed at a single tumor which triggers resulting shrinkage of tumors well outside of the field of radiation. It is assumed to be an immune response in the irradiated tumor triggered by using a low, minimally-ablative dose of radiation. Once acknowledged as a very rare event, the growing use of immuno-oncology drugs in combination with radiotherapy has led to increasing reports of abscopal responses in a range of cancers, including lung, breast, and urogenital cancers and melanoma. No such reports have come from studies in prostate cancer with checkpoint inhibitors either alone or in combination with radiotherapy, leading to this cancer gaining a reputation as a "non-immunological" cancer.

The DARRT-1 study involved 15 men with mCRPC post-taxane and ADT therapy. They received experimental sphingosine-1-phosphate inhibitor, Veyonda, in combination with a palliative dose of external beam radiotherapy to a single tumor, typically a lymph node cluster. An abscopal response was determined on the basis of scans of other nonirradiated soft tissue lesions.

Dr. Graham Kelly, Noxopharm CEO, said, "To our knowledge, this is the first time that anyone has been able to obtain a meaningful abscopal response rate in prostate cancer. Prostate cancer has developed a reputation as a cancer with poor immune responsiveness, but this outcome suggests that this isn’t the case when a drug with the appropriate effect on the immune system is used. Today’s result positions Veyonda at the forefront of this emerging area of oncology and suggests that we have an exciting new prospective treatment for end-stage prostate cancer."

On May 6, 2020 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket"), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare disorders, reported financial results for the quarter that ended March 31, 2020, along with an update on the Company’s key pipeline developments, business operations and upcoming milestones (Press release, Rocket Pharmaceuticals, MAY 6, 2020, View Source [SID1234557156]).

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"During the first quarter, we continued to advance five programs across both the AAV and Lenti platforms," said Gaurav Shah, M.D., Chief Executive Officer and President of Rocket. "Notably this quarter, we completed patient treatment in the low dose cohort for RP-A501 in the Phase 1 Danon Disease trial with no dose-limiting toxicities, and are now pleased to report FDA and IDSMC clearance to advance to a higher dose cohort. This has been an important priority for us as Danon Disease affects so many young patients with devastating heart, muscle and CNS manifestations. We also continued to progress our clinical programs for FA, LAD-I, and PKD. Rocket is at an exciting stage of growth, with a rich pipeline of development-stage opportunities and the potential to transform the lives of patients afflicted with rare disease. In the coming months, we look forward to presenting updated FA ‘Process A’ and LAD-I ‘Process B’ data at ASGCT (Free ASGCT Whitepaper), treating our first patient in a higher dose cohort for RP-A501, and bringing our fifth program, IMO, to the clinic."

Dr. Shah continued, "With regard to the COVID-19 pandemic, we are well-positioned overall to continue our progress while we monitor and adjust to this challenging global crisis. We have experienced modest COVID-19-related pauses in patient enrollment and follow-up that are being managed on a patient-by-patient basis, along with some delays in data collection. Nonetheless, we remain on track for providing updates on our lentiviral pipeline. Assuming that COVID-19 associated delays have shorter-term impact, we remain committed to providing data for Danon by the end of the year. Lastly, we continue to actively monitor the pandemic and refine operations to support the complete safety and well-being of our patients, employees and community."

Key Pipelines and Operational Updates

First cohort of patients completed in Phase 1 trial of RP-A501 for Danon Disease, with U.S. Food and Drug Administration (FDA) and Independent Data Safety Monitoring Committee (IDSMC) clearance to initiate a higher dose cohort. Rocket has treated the first three patients at the low dose of 6.7×1013 vector genomes (vg)/kilogram (kg). No investigational product (IP)-related dose-limiting safety concerns have been observed in any of the three patients treated. The low dose cohort demonstrates a favorable safety profile, and the Company has received clearance from the IDSMC and the FDA to move to a higher dose cohort. Patient treatment in this cohort is anticipated in the third quarter, with preliminary Danon data readout in the fourth quarter.
The Fanconi Anemia (FA) and Leukocyte Adhesion Deficiency-I (LAD-I) clinical studies have continued to progress. Updated data from FANCOLEN-I (utilizing "Process A") will be presented at ASGCT (Free ASGCT Whitepaper), as will updates from the Phase 1 LAD-I study utilizing "Process B." Updates on FA "Process B" data will be presented in the fourth quarter.
The Research & Development (R&D) and Chemistry, Manufacturing and Controls (CMC) facility in Cranbury, New Jersey resumes construction after COVID-19 associated delays. Build-out of the New Jersey facility experienced some construction delays associated with the COVID-19 pandemic, but resumed on May 4, 2020. Occupancy in the new facility is still anticipated in the first half of 2020. Approximately half of the newly constructed 103,720 square foot facility will be dedicated to adeno-associated virus (AAV) Current Good Manufacturing Practice (cGMP) manufacturing. As previously guided, the first cGMP clinical product release is expected in 2021.
Recent publications for FA and Danon Disease provide greater insight into Rocket’s approach for ongoing clinical trials. In February, the peer-reviewed journal Annals of Hematology published Rocket’s comprehensive review of somatic mosaicism in Fanconi Anemia (FA), written in collaboration with Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and other international research partners. The article, entitled, "Mosaicism in Fanconi Anemia: Concise review and evaluation of published cases with focus on clinical course of blood count normalization," highlights research describing mosaicism in FA and supports Rocket’s approach of treating patients with RP-L102 without any pre-treatment conditioning measures. In March, Science Translational Medicine published positive preclinical data on Rocket’s Danon program, demonstrating that vector-mediated transfer of LAMP2B to deficient mice improved heart function and survival. The article, "AAV9.LAMP2B Reverses Metabolic and Physiologic Multiorgan Dysfunction in a Murine Model of Danon Disease," underscores the promise of Rocket’s AAV-based gene therapy candidate for Danon, RP-A501.
Rocket recognizes Rare Disease Day with an event at New York City’s Carnegie Hall. On February 29, 2020, Rocket hosted its second annual Rare Disease Day event highlighting the theme "I Am Rare, Hear Me Roar." Over 200 members of the rare disease and broader New York City biotech communities heard from patients and their families, learning more about the impact of rare disease and how to become partners in the fight to find new treatment options. The event culminated with the lighting of the Empire State Building in Rare Disease Day colors, honoring all those affected by rare disease.
Anticipated Milestones

FA (RP-L102)
Additional "Process A" data update (2Q)
Preliminary "Process B" data (4Q)
Danon Disease (RP-A501)
First patient treatment in higher dose (3Q)
Preliminary Phase 1 data (4Q)
LAD-I (RP-L201)
Phase 1 data update on first patient (2Q)
Initiate Phase 2 study (4Q)
Phase 1 data update (4Q)
PKD (RP-L301)
First patient treatment (3Q, previously 2Q)
Preliminary Phase 1 data (4Q)
IMO (RP-L401)
Initiation of clinical study (4Q)
Upcoming Investor Conferences

BofA Securities 2020 Virtual Health Care Conference, May 13, 2020
Jefferies Virtual Healthcare Conference, June 2-4, 2020
Third Quarter Financial Results

Cash position. Cash, cash equivalents and investments as of March 31, 2020, were $275.9 million.
Debt. Our balance sheet includes $52.0 million of fully convertible notes.
R&D expenses. Research and development expenses were $17.0 million for the three months ended March 31, 2020, compared to $15.1 million for the three months ended March 31, 2019. The increase was primarily driven by an increase in clinical trial expenses of $1.5 million.
G&A expenses. General and administrative expenses were $7.2 million for the three months ended March 31, 2020, compared to $3.8 million for the three months ended March 31, 2019. The increase was primarily driven by fees incurred for the convertible notes exchange of $1.6 million, and an increase in compensation expense of $1.3 million due to increased headcount.
Net loss. Net loss was $24.7 million or $0.45 per share (basic and diluted) for the three months ended March 31, 2020, compared to $19.5 million or $0.43 per share (basic and diluted) for the three months ended March 31, 2019.
Shares outstanding. 55,126,474 shares of common stock were outstanding as of March 31, 2020.
Financial Guidance

Cash position. As of March 31, 2020, we had cash, cash equivalents and investments of $275.9 million. Rocket expects such resources will be sufficient to fund its operations into 2022.

On May 6, 2020 InteRNA Technologies reported regulatory approvals in the Netherlands and Belgium for the initiation of the first-in-human (Phase I) clinical trial testing its lead microRNA candidate, INT-1B3, in patients with advanced solid tumors (Press release, InteRNA Technologies, MAY 6, 2020, View Source [SID1234557155]). INT-1B3 is a lipid nanoparticle (LNP) formulated, chemically modified miR-193a-3p mimic that can be delivered by systemic administration to cancer cells. Due to the ongoing COVID-19 pandemic, clinical trial initiation has been delayed and is now anticipated to start during H2 2020. The Company will provide an update once the trial has officially launched.

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The study is a multicentric, open-label and multiple ascending dose clinical trial that will investigate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of INT-1B3 in patients with advanced solid tumors. The study is expected to enroll a total of up to 80 patients at 12 clinical centers in the United States and Europe. The first part of the trial is a Phase Ia dose escalation study, conducted in the Netherlands and Belgium, which will enroll approximately 30 patients with advanced solid tumors. These patients will receive INT-1B3 via infusions twice weekly in 21-day cycles. Subsequently, approximately 50 patients with either hepatocellular carcinoma or triple negative breast cancer will be enrolled in the Phase Ib dose expansion part of the trial. Initial data readout from the Phase Ia study is expected in the end of 2021.

"The multi-targeted nature of microRNAs represents a novel approach to treating a broad range of cancer indications by effectively targeting several biochemical pathways simultaneously," said Dr. Roel Schaapveld, CEO of InteRNA Technologies. "Driven by the promise of microRNAs as a treatment modality in cancer, our understanding of the underlying mechanism of action of INT-1B3 and the identification of a delivery vehicle for optimized performance, our primary focus has been on preparing our lead candidate for first-in-human clinical trials. As such, we are truly excited to bring INT-1B3 into the clinic and to gain deeper insights on how it reacts against solid tumors."

"INT-1B3 is a promising and novel anti-cancer approach with anti-tumor potential involving direct effects on tumor cells and modulation of the immunosuppressive tumor microenvironment leading to immune system activation," added Prof. Dr. Emile Voest, Chairman of InteRNA’s Scientific Advisory Board and Medical Director of the Netherlands Cancer Institute in Amsterdam. "The safety profile and significant anti-tumor efficacy demonstrated in preclinical studies provide a strong basis for first-in-human studies with INT-1B3."

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in cell cycle arrest, induction of apoptosis and immunogenic tumor cell death (ICD); as well as downregulation of the adenosine-A2A receptor pathway and immunosuppressive FoxP3/Lag3 Tregs and monocytic myeloid-derived suppressor cells (mMDSCs). As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ Teffs leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment. The created T cell-mediated immune response activity is also transferrable to naive mice via adoptive T cell transfer.

On May 6, 2020 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported its business update for the quarter ending March 31, 2020, and provides an update on its progress of clinical trial portfolio taking into account the impact of the Covid-19 pandemic (Press release, Transgene, MAY 6, 2020, View Source [SID1234557154]).

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Operating revenue

The following table summarizes the first quarter operating revenue for 2020 compared to the same period in 2019:

During the first quarter of 2020, revenue from collaborative and licensing agreements was mainly composed of the revenue under the collaboration with AstraZeneca.

As of March 31, 2020, government financing for research expenditures mainly consisted of 25% of the research tax credit expected for 2020 (€1.5 million in the first quarter of 2020, as in 2019).

Cash, cash equivalents and other financial assets

In the first quarter of 2020, Transgene’s cash burn was €8.0 million, compared to €7.8 million for the same period in 2019. Cash, cash equivalents and other financial assets stood at €35.3 million as of March 31, 2020, compared to €43.3 million as of December 31, 2019.

This cash position does not include the €20 million credit facility available for the Company until June 2022.

Summary of key ongoing clinical trials and expected milestones

Transgene continues to monitor the development of the of Covid-19 pandemic and its potential consequences on its activities. To-date the pandemic has had limited impact.

Transgene’s teams have been mostly working from home to ensure business continuity. The commitment of our employees and the measures taken to provide a safe environment have allowed Transgene to maintain activity in the labs in order to ensure the progress of our strategic research projects and to operate our pilot manufacturing unit. Encouragingly, we expect our labs to be operating at close to normal levels starting next week.
As of today, we do not anticipate significant delays to our clinical readouts.
Some key congresses, such as AACR (Free AACR Whitepaper), have been rescheduled as virtual events. Transgene and its partners intend to present preclinical data on myvac and BT-001 at "virtual" AACR (Free AACR Whitepaper) (Session II). The abstracts of the posters to be presented will be available on May 15, 2020.
TG4001

+ Bavencio

(avelumab)
Phase 2

Targets: HPV16 E6 and E7 oncoproteins

HPV-positive cancers including oropharyngeal head and neck cancer – 2nd line

Clinical collaboration with Merck KGaA and Pfizer, for the supply of avelumab
All patients required to perform the interim analysis have been enrolled
Interim Phase 2 results on track for 2Q 2020

myvac

TG4050

Phase 1

Targets: tumor neoantigens

Ovarian cancer – after first-line surgery and adjuvant therapy

Trial authorized in the United States and in France
Principal investigator: Matthew Block (Mayo Clinic)
First patient enrolled in January 2020
First data on track for 1H 2021

myvac

TG4050

Phase 1

HPV-negative head and neck cancer – after surgery and adjuvant therapy

Trial authorized in the United Kingdom and in France
Principal investigator: Christian Ottensmeier (Southampton University)
First patient enrolled in January 2020
First data on track for 1H 2021
Data demonstrating high accuracy of AI-based neoantigen prediction for the design of TG4050 will be presented at AACR (Free AACR Whitepaper)

TG6002

Phase 1/2a

Payload: FCU1 for the local production of a 5-FU chemotherapy

Gastro-intestinal adenocarcinoma (colorectal cancer for Phase 2) – Intravenous (IV) route

Multicenter trial ongoing in Belgium, France and Spain
Last dose cohorts currently being evaluated (Phase 1 part)
First results of the Phase 1 part expected for late of 2Q / early 3Q 2020

TG6002

Phase 1/2a

Colorectal cancer with liver metastasis – Intrahepatic artery (IHA) route

Multicenter trial authorized in the United Kingdom
First patient treated in February 2020; enrollment paused for several weeks due to Covid-19
The Company will provide an update in September 2020 on the expected timing of the release of the first Phase 1 data

Invir.IO

BT-001

Phase 1/2

Payload: anti-CTLA4 antibody and GM-CSF cytokine

Solid tumors

Collaboration with BioInvent
First clinical trial application submitted
Presentation of very encouraging preclinical results at AACR (Free AACR Whitepaper)

First clinical trial expected to start before the end of 2020

Outlook

Transgene expects its cash burn for 2020 to be around €25 million, based on its current development plan.

Post-closing events

On May 4, 2020, Transgene announced the sale of its proprietary DuckCelt-T17 cell line to Vaxxel, a French biotech start up focused on respiratory vaccines. As a result of this transaction, Transgene has become a significant shareholder in Vaxxel. Vaxxel will use the DuckCelt-T17 cell line to enable the production of prophylactic vaccines against respiratory viruses (Metapneumovirus and Respiratory Syncytial Virus).

On April 9, 2020, Transgene sold its entire 8.25% holding in ElsaLys Biotech in a private operation.

On May 6, 2020 Oncology Venture A/S ("OV" or the "Company") reported that is has secured a US $5 million (50 million SEK) investment and entered into a share subscription agreement with Global Corporate Finance (Press release, Oncology Venture, MAY 6, 2020, View Source [SID1234557152]).

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The investment and share subscription agreement are with Global Corporate Finance (GCF) (New York City, NY, U.S.) and will support Oncology Venture’s continuing development and commercialization of its prioritized pipeline of cancer drugs together with their DRP companion diagnostics. GCF is a private family office that invests in both public and private companies across the globe.

Steve Carchedi, CEO of Oncology Venture, commented "We are thrilled to have the long-term investment and support of GCF to help continue advancing our prioritized drug programs towards near-term value inflection points. We further welcome this broadening of our investor base to include a prominent U.S. based family fund, as we push towards securing institutional investment support in the U.S."

Nino Scalamandre, Director of GCF, noted "We believe there is a significant upside potential in Oncology Venture, both due to the company’s late stage drug development programs and its unique DRP technology platform, and we are pleased to invest in the company at this stage to help it unlock its full potential and bring new cancer therapies to patients."

The main conditions and structure of the financing agreement are:

The agreement runs for 36 months, during which time Oncology Venture can solely decide to exercise investment by GCF in five (5) tranches of up to US $1 million (10 million SEK) each against issuing Company shares to GCF.
The share subscription price in each tranche shall be calculated as 95% of the daily volume weighted average price (VWAP) of the Company’s shares for the five (5) consecutive trading days following the date of a draw down notice from OV.
The financing costs for Oncology Venture are five percent (5%) of the total commitment of US $5 million (SEK 50 million), excluding legal and administrative costs.