On March 29, 2022 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that the U.S. Food and Drug Administration (FDA) has cleared UroGen’s Investigational New Drug (IND) application to begin a novel Phase 1 clinical study of the anti-CTLA-4 immunotherapy UGN-301 (zalifrelimab) in patients with recurrent NMIBC (Press release, UroGen Pharma, MAR 29, 2022, View Source [SID1234611132]). The multi-arm Phase 1 study is expected to start in April and support the development of UGN-301 in high-grade (HG) NMIBC.

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UroGen’s pursuit to harness the power of the immune system to fight cancer begins with UGN-301, which UroGen views as a potential cornerstone of a variety of combination therapies targeting recurrent NMIBC and high-grade cancers. UroGen initially plans to combine UGN-301 with UGN-201, the Company’s proprietary formulation of imiquimod a toll-like receptor 7 (TLR7) agonist, which has demonstrated single-agent activity in high-risk bladder cancer patients.

The novel study design will utilize a Master Protocol that UroGen believes is a more efficient and streamlined approach to development. It will provide more flexibility to add study arms as the trial progresses and increase efficiency and reduces costs. UroGen expects the Master Protocol will allow the Company to more quickly evaluate safety, tolerability and dosing of UGN-301 in combination with additional immunomodulators and chemotherapies, with the goal of developing optimized medicines for patients.

"We are pleased that our IND application was cleared to proceed, and we can begin to explore our innovative approach to meeting the high unmet needs in bladder cancer, especially for patients with high-grade disease," says Mark Schoenberg, Chief Medical Officer, UroGen Pharma. "Intravesical delivery of combination therapies is unique with the goal of improving efficacy while avoiding the toxicities associated with systemic treatment of immunotherapies. Our proprietary technology enables local delivery of treatments, which provide opportunities to pursue several promising drug combinations."

Unmet Needs in Bladder Cancer
Bladder cancers are described as muscle invasive or non-muscle invasive based on whether they have invaded the wall of the bladder. HG NMIBC is associated with an increased risk of recurrence and progression. Approximately 25,000 people are diagnosed with HG NMIBC annually. Transurethral resection of bladder tumor (TURBT) followed by intravesical bacillus Calmette-Guérin (BCG) is currently the standard of care for treatment of HG NMIBC.

HG NMIBC patient response to BCG therapy has long been interpreted as evidence that bladder cancer is sensitive to immunotherapy. Unfortunately, many patients with HG disease do not respond to BCG or relapse following therapy. In these cases, patients have limited therapeutic options and often proceed to bladder removal as a means of forestalling disease progression which has a significant association with cancer specific mortality. UroGen’s proprietary RTGel technology provides a novel method for delivering alternatives to BCG including immunomodulatory molecules such as UGN-301 as well as chemotherapeutic agents and other drugs with diverse molecular characteristics and sizes.

On March 29, 2022 Mursla, a novel multi-omics exosome characterisation company, reported that it has secured mentorship support from Roche Diagnostics Ltd for a new liquid biopsy prospective pilot study for liver cancer surveillance through MedCity’s Collaborate to Innovate: London Diagnostics programme (Press release, Mursla, MAR 29, 2022, View Source [SID1234611153]). Liver cancer is the third most common cause of premature cancer death worldwide and its incidence has increased significantly over other forms of cancer in the last three decades.

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Mursla’s aim is to develop a blood test that can detect early-stage hepatocellular carcinoma (HCC) more effectively than the current standard of care. To this end, the primary objective of the prospective pilot study is to select and confirm the relevance of novel HCC biomarkers for a larger longitudinal study demonstrating high clinical performance in a more tailored cohort. A secondary objective is the assessment of Mursla’s tissue-specific and multi-omics exosome approach as proof of concept for the development of other related cancer liquid biopsy tests.

To enable the pilot study, Mursla will leverage its proprietary multi-omics exosome characterisation platform technology for the discovery and profiling of exosome phenotypes, ExoPheno. It consists of proprietary and patented technologies, which integrate wet lab (validated exosome tissue-of-origin markers, pre-analytical multi-omics sequencing workflow and ultrasensitive exosome marker detection systems) and dry lab analysis via machine learning.

Hundreds of blood samples will be prospectively collected by Tissue Access for Patient Benefit (TAPB), a University of College London (UCL) and NHS initiative based at the Royal Free Hospital in London, UK, and by Biobanco-IMM Lisbon Academic Medical Center Portugal in collaboration with Gastroenterology Service at Hospital de Santa Maria in Lisbon, Portugal. The samples will then be characterised by ExoPheno to establish differences in the multi-omics cargo of specific exosome sub-populations between patients with various chronic liver diseases and cancer at various stages. In addition, Roche Diagnostics Ltd will support Mursla in bringing its solution to the clinic by sharing its expertise and best practice in evidence generation, scaling up and market access.

First generation liquid biopsy tests measure circulating tumor DNA (ctDNA) mutations and/or epigenetic markers (such as ctDNA methylation or fragmentation patterns) with low positive predictive value (PPV) for early-stage cancer detection, potentially leading to millions of distressing false positives. Mursla intends to improve PPV with its novel ExoPheno platform which:

Uses tissue-of-origin markers to capture tissue-specific exosomes in blood.
Detects specific multi-omics disease markers (including DNA, RNA, proteins, lipids and metabolites) contained in exosomes, mirroring the parental cell with disease.
Focuses on dynamic information released by living cells in exosomes, not by dying cells in the case of ctDNA.
Gerard Harkin, Head of Innovation UK & Ireland, Roche Diagnostics Ltd commented: "We are delighted to support the MedCity programme that encourages innovations in diagnostics and to provide in-kind mentorship to Mursla. In the field of cancer, we see the potential for new technologies to significantly improve the existing standard of care."

Pierre Arsène, Founder and CEO, Mursla added: "We are very pleased to receive the support of Roche’s UK team for the application of our novel exosome characterisation platform in early-stage liver cancer detection and beyond. We believe that the specific multi-omics information carried by blood exosomes from the tumor and its microenvironment will enable the next generation of liquid biopsy tests."

The collaboration has been enabled via Collaborate to Innovate: London Diagnostics, a MedCity programme, which is part grant-funded by the London Economic Action Partnership (LEAP). Collaborate to Innovate is an initiative that streamlines the process for building effective collaborations between SMEs and academia, commercial and non-profit partners, by helping SMEs to refine and validate their promising early-stage innovative scientific developments in their journey to provide established commercial solutions.

Mursla is one of nine successful SMEs to be selected to proceed with its study having been chosen by a panel comprising leading experts from Cancer Research UK, NHS England, BIVDA, LifeArc and world leading London academic institutions. Mursla will retain full intellectual and economic rights.

On March 29, 2022 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported the first patient has been dosed in the Phase 1b/2 study of RBN-2397 in combination with the anti-PD-1 checkpoint inhibitor therapy, pembrolizumab, in patients with squamous cell carcinoma of the lung (SCCL) (Press release, Ribon Therapeutics, MAR 29, 2022, View Source [SID1234611092]). RBN-2397 is a small molecule inhibitor of PARP7 being evaluated in multiple clinical trials for the treatment of cancer.

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"RBN-2397 is a selective PARP7 inhibitor designed to activate the Type I interferon response in tumor cells and overcome a major limitation of immune checkpoint inhibitors (ICI). Combining RBN-2397 with an anti-PD-1 ICI is expected to treat a variety of tumor types including SCCL, a devastating disease representing the second most common form of non-small cell lung cancer," said Prakash Raman, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "The initiation of the Phase 1b/2 study of RBN-2397 with pembrolizumab will enable us to further understand the potential utility of this combination therapy."

"PARP7 is amplified and highly expressed in SCCL and certain other solid tumors. We have seen encouraging results from our ongoing Phase 1 trial of RBN-2397 as a monotherapy, which is currently evaluating a number of defined expansion cohorts, including patients with SCCL," said Sudha Parasuraman, M.D., Chief Medical Officer, Ribon Therapeutics. "The RBN-2397- pembrolizumab combination is anticipated to drive activated T cells into tumors with the potential to overcome resistance to ICIs. We look forward to evaluating this biology-driven combination in the clinical setting for patients with SCCL who are in need of new therapeutic options."

About RBN-2397

RBN-2397 is an orally available small molecule inhibitor of PARP7 being developed for the treatment cancer. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors and in a Phase 1b/2 clinical trial in combination with pembrolizumab. PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.

On March 29, 2022 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported business highlights and financial results for the fourth quarter and full-year ended December 31, 2021 (Press release, Delcath Systems, MAR 29, 2022, View Source [SID1234611117]).

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Recent Business Highlights

During and since the fourth quarter, Delcath:

Reported updated positive phase 3 FOCUS trial results for HEPZATO Kit (melphalan hydrochloride for injection/hepatic delivery system) for the treatment of patients with unresectable liver-dominant metastatic ocular melanoma, including initial survival data analysis

Confirmed guidance for the mid-year Class 2 resubmission of the NDA to FDA

Resumed direct responsibility for sales, marketing, and distribution activities for the CHEMOSAT Hepatic Delivery System in all of Europe

Achieved medical device regulation certification for CHEMOSAT in Europe

Appointed David Hoffman as General Counsel and Chief Compliance Officer and Anthony Dias as Vice President of Finance

In addition, during and since the fourth quarter, independent investigators published:

Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers in the journal Cardiovascular and Interventional Radiology1

Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma in the journal Melanoma Research2

Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience in the journal Cancers3

Initiation of Chemosaturation with Percutaneous Hepatic Perfusion Program in Interventional Radiology Department in the journal Cureus4

"Since the end of the third quarter, we have updated our previously reported positive phase 3 data with survival data, resumed direct sales of CHEMOSAT in Europe, and strengthened our leadership team," said Gerard Michel, CEO of Delcath. "Each of these achievements support our strategic priorities – filing of the HEPZATO NDA in mid-2022, preparing for the subsequent US launch when approved, and expanding the development of HEPZATO and CHEMOSAT into additional areas of high unmet need. We look forward to a pre-NDA meeting with FDA in the coming weeks."

Fourth Quarter 2021 Results

Income Statement Highlights.

Product revenue for the three months ended December 31, 2021, was approximately $0.2 million, compared to $0.4 million for the prior year quarter from sales of CHEMOSAT in Europe. Other income for the quarter was $1.9 million compared to $0.1 million in the prior year quarter with the increase primarily due to the acceleration of deferred revenue caused by the termination of the medac license agreement. Research and development expenses for the quarter were $3.6 million compared to $2.7 million in the prior year quarter. Selling, general and administrative expenses for the quarter were approximately $3.0 million compared to $4.5 million in the prior year quarter. Total operating expenses for the quarter were $6.6 million compared with $7.3 million in the prior year quarter. Expenses for the quarter included approximately $1.6 million of stock option expense compared to $3.5 million in the prior year quarter.

The Company recorded a net loss for the three months ended December 31, 2021, of $5.3 million, compared to a net loss of $7.0 million for the same period in 2020.

Full-Year 2021 Results

Product revenue for the year ended December 31, 2021, was approximately $1.3 million, compared to $1.2 million for the prior year from sales of CHEMOSAT in Europe. Other income for the year was $2.2 million compared to $0.5 million in the prior year with the increase primarily due to the acceleration of deferred revenue caused by the termination of the medac license agreement. Research and development expenses for the year were $13.8 million compared to $11.2 million in the prior year. Selling, general and administrative expenses for the year were approximately $13.6 million compared to $11.2 million in the prior year. Total operating expenses for the year were $27.4 million compared with $22.3 million in the prior year. Expenses for the year included approximately $7.8 million of stock option expense compared to $3.9 million in the prior year.

The Company recorded a net loss for the year ended December 31, 2021, of $25.6 million, compared to a net loss of $24.2 million for the year ended December 31, 2020.

Balance Sheet Highlights.

On December 31, 2021, the company had cash, cash equivalents and restricted cash totaling $27.0 million, as compared to cash, cash equivalents and restricted cash totaling $28.7 million on December 31, 2020. During the three months ended December 31, 2021 and December 31, 2020, we used $6.4 million and $5.0 million, respectively, of cash in our operating activities.

On March 29, 2022 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported that a patient with relapsed/refractory acute myeloid leukemia or AML in a monotherapy arm of its on-going Phase 1b trial evaluating adult patients with AML, has received an allogeneic stem cell transplant subsequent to receiving APVO436 and experiencing significant reduction in bone marrow blasts (Press release, Aptevo Therapeutics, MAR 29, 2022, View Source [SID1234611133]). This follows the Company’s previous announcement that a patient receiving combination therapy is also moving to transplant after one cycle of therapy.

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"We are very pleased to report that a refractory secondary AML patient, after receiving APVO436 as monotherapy, experienced a significant reduction in bone marrow blasts, tolerated the treatment well, experienced clinical benefit and was therefore able to proceed to allogeneic transplant. Prior to trial entry, this patient had refractory disease after receiving multiple other lines of therapy and had a very poor prognosis. There were few therapeutic options left with which to fight the disease," said Justin Watts, MD, Associate Professor of Medicine, Chief, Leukemia Section at the University of Miami Sylvester Comprehensive Cancer Center and treating investigator. "Without APVO436, this patient would not have proceeded to transplant, a highly desirable outcome for patients with AML."

APVO436 is currently being evaluated in a Phase 1b expansion trial for adult patients with AML in a multi-center, multi-cohort study of up to 90 patients who will receive either APVO436 in combination with standard of care chemotherapies or as monotherapy. In 2021, the Company announced results from its Phase 1b dose escalation trial in patients with both AML and myelodysplastic syndrome or MDS. Results showed that APVO436 exhibited a favorable safety profile with acceptable tolerability and generally manageable drug-related adverse events. Promising clinical activity was also observed in 11 of 40 patients (27.5%) in the dose escalation part of the study and reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021. This included two complete remissions in patients with AML and three complete marrow responses in patients with MDS.

"We are excited that a patient receiving monotherapy proceeded to transplant in the expansion trial, further demonstrating APVO436 clinical activity in AML and in support of our findings from the dose escalation part of the trial reported last year, said Dirk Huebner, MD, Senior Medical Advisor at Aptevo. "While our clinical evaluation of APVO436 is still in early stages, the safety profile, overall tolerability, and clinical activity reported to date demonstrate the potential for APVO436 to have meaningful impact on the AML treatment paradigm."

About APVO436

Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo’s lead proprietary drug candidate, APVO436 is a bispecific CD3xCD123 ADAPTIR that is designed to redirect the immune system of the patient to destroy leukemia cells expressing the target CD123 molecule on their surface. This antibody-like recombinant protein therapeutic is designed to engage both leukemia cells and T-cells of the immune system and bring them closely together to trigger the destruction of leukemia cells. APVO436 has been engineered using Aptevo’s proprietary and enabling bioengineering methods and is designed to reduce the likelihood and severity of cytokine release syndrome (CRS). APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.