On March 29, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported pipeline and business progress and fourth quarter and full year 2021 financial results (Press release, Nuvalent, MAR 29, 2022, View Source [SID1234611091]).

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As part of today’s update, Nuvalent is announcing that its Investigational New Drug (IND) application for NVL-655 for the treatment of ALK-positive NSCLC and other solid tumors was cleared by the U.S. Food and Drug Administration (FDA). NVL-655 is a novel ALK-selective inhibitor designed with the aim to address the clinical challenges of emergent treatment resistance, central nervous system (CNS)-related adverse events, and brain metastases that may limit the use of currently available ALK inhibitors. Nuvalent plans to initiate the ALKOVE-1 Phase 1/2 study of NVL-655 for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors in the second quarter of 2022.

"The Nuvalent team has continued to demonstrate the ability to discover novel molecules with preclinical profiles suggesting best-in-class potential and to progress them efficiently into clinical development. With the clearance of our IND for NVL-655, Nuvalent is on track to have two parallel lead compounds in clinical trials by mid-year," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We believe we are well positioned with two clinical-stage, novel product candidates in areas of significant medical need, and sustainable internal discovery efforts with the goal of delivering multiple additional product candidates. I am incredibly proud of all that this team has accomplished and their continued dedication to advancing new potential therapeutic options for patients in need."

Recent Pipeline Highlights

Enrollment Ongoing in ARROS-1 Trial of NVL-520 for Patients with Advanced ROS1-positive NSCLC: Nuvalent is actively enrolling patients in the Phase 1 portion of its ARROS-1 clinical trial, a Phase 1/2 study evaluating NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors. NVL-520, Nuvalent’s lead product candidate, is a novel ROS1-selective inhibitor designed with the aim to address the clinical challenges of emergent treatment resistance, CNS adverse events, and brain metastases that may limit the use of currently available ROS1 kinase inhibitors.
Discovery Pipeline Advancing toward Selection of Next Development Candidates: Nuvalent continues to advance its early pipeline efforts with multiple discovery-stage research programs. The company expects to nominate product candidates in 2022 for its discovery programs directed toward ALK IXDN compound resistance mutations and HER2 exon 20 insertions.
Recent Business Highlights

Strengthened Board of Directors with Appointment of Emily Drabant Conley, Ph.D.: In February 2022, Nuvalent appointed Emily Drabant Conley, Ph.D., Chief Executive Officer of Federation Bio, to its Board of Directors. Dr. Conley’s work has contributed to industry-shaping advances in genomics that empower patients and clinicians with actionable health data. Prior to Federation Bio, she spent over a decade at 23andMe where, as Vice President of Business Development, she was instrumental in powering the company’s growth from 30 employees into a household name.
Fourth Quarter and Full Year 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $288.1 million as of December 31, 2021. Nuvalent expects that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operations into 2024.
R&D Expenses: Research and development (R&D) expenses were $13.2 million for the quarter ended December 31, 2021, and $35.6 million for the year ended December 31, 2021.
G&A Expenses: General and administrative (G&A) expenses were $4.2 million for the quarter ended December 31, 2021, and $10.3 million for the year ended December 31, 2021.
Net Loss: Net loss was $17.3 million for the quarter ended December 31, 2021, and $46.3 million for the year ended December 31, 2021.

O March 29, 2022 HTG Molecular Diagnostics, Inc. (Nasdaq: HTGM) (HTG), a life science company advancing precision medicine through its innovative transcriptome-wide profiling technology, reported its financial results for the year ended December 31, 2021 (Press release, HTG Molecular Diagnostics, MAR 29, 2022, View Source [SID1234611116]).

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Recent Business Highlights

HTG Transcriptome Panel ("HTP") revenue continued to increase in the fourth quarter of 2021, ending the year as the top selling assay at approximately 16% of total revenue, just 5 months after commercial sales availability.

Announced the expansion of its therapeutics team with the addition of several highly experienced professionals, led by Stephen Barat, Ph.D., a drug development veteran who most recently served with the Janssen Pharmaceutical Companies of Johnson and Johnson (Janssen).

Expanded its HTG Therapeutics business unit’s Scientific Advisory Board with the addition of Jerald Radich, M.D., a pioneer in the fields of leukemia research and molecular genetics, and Robert Spitale, Ph.D., Associate Director and Associate Dean of Research in the School of Pharmacy and Pharmaceutical Services at the University of California, Irvine.

Added extensive biopharmaceutical industry experience and therapeutic depth to its Board of Directors with the addition of Christopher Kiritsy, formerly of KOS Pharmaceuticals.

Completed a private placement of its securities for gross proceeds of approximately $7.5 million.

Full Year 2021 Financial Highlights:

Total revenue for the year ended December 31, 2021 was $8.9 million, compared with $8.5 million for the year ended December 31, 2020.

Product and product-related services revenue increased by 13% for the year ended December 31, 2021 to $8.9 million, compared with $7.9 million for the year ended December 31, 2020. Revenue for the year ended December 31, 2021 included $1.4 million of revenue recognized from the sale of HTP assays and sample processing services. Revenue for the year ended December 31, 2020 included $0.7 million of collaborative development services revenue.

Net loss from operations for the year ended December 31, 2021 was $17.1 million, compared with $20.9 million for the year ended December 31, 2020. Net loss per share was $(2.47) for the year ended December 31, 2021 compared with $(4.51) for the year ended December 31, 2020.

Cash, cash equivalents and short-term available-for-sale securities totaled $21.9 million as of December 31, 2021, with current liabilities of approximately $9.9 million and non-current liabilities of $10.1 million.

Conference Call and Webcast:

HTG will host a conference call for the investment community today beginning at 4:30 p.m. Eastern Time. Conference call and webcast details are as follows:

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.