On August 9, 2022 BostonGene reported the online publication of the manuscript, "Precise reconstruction of the tumor microenvironment using bulk RNA-seq and a unique machine learning algorithm trained on artificial transcriptomes" in Cancer Cell, a premier peer-reviewed scientific journal that publishes high impact results in cancer research and oncology (Press release, BostonGene, AUG 9, 2022, View Source [SID1234617959]). The study demonstrated the ability of the BostonGene-developed unique and robust machine learning (ML) algorithm named Kassandra to digitally reconstruct the tissue tumor microenvironment (TME) and blood cellular composition, identifying over 50 unique cell populations in total from RNA-seq derived from both archival and fresh tissues. These results indicate that cellular deconvolution can be utilized in future clinical applications to predict blood and tissue microenvironment composition, a critical factor in cancer pathogenesis, clinical outcome, and therapeutic resistance.

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Kassandra was trained on a broad collection of > 9,400 tissue and blood-sorted cell RNA profiles incorporated into millions of artificial transcriptomes for this research study. To increase the stability and robustness of BostonGene’s decision-tree ML deconvolution algorithm, bioinformatic correction for technical and biological variability, aberrant cancer cell expression inclusion, and accurate quantification and normalization of transcript expression were applied. Results of the study showed that Kassandra recognizes 51 unique subpopulations and accurately deconvolves less well-characterized stromal and immune elements of prospectively collected lung and kidney cancer tumors. Kassandra-based TME reconstruction found the presence of PD1-positive CD8+ T cells strongly correlates with immunotherapy response and PD-L1 protein levels detected by immunohistochemistry, the established immunotherapy response biomarker, indicating that in the future RNA-seq-based cellular deconvolution could support oncology clinical decision-making.

"Our findings demonstrate the importance of cellular deconvolution based on RNA-seq to accurately understand the composition and activity of the tumor and the microenvironment to improve treatment outcomes," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "We look forward to further developing the Kassandra algorithm and showing its clinical applicability in precision oncology.

On August 9, 2022 Fore Biotherapeutics, a precision oncology company developing treatments for patients with genetically defined cancers whose current treatment options are limited, reported that data from the ongoing Phase 1/2a study of lead asset, FORE8394, will be presented in the Developmental Therapeutics poster session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) taking place in Paris, France, September 9-13, 2022 (Press release, Fore Biotherapeutics, AUG 9, 2022, View Source [SID1234617958]).

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The Phase 1/2a open-label study is assessing FORE8394, a next-generation BRAF inhibitor, in patients with advanced solid and CNS tumors with activating BRAF alterations. The poster presentation will report interim analysis in adults (≥18 years) with V600+ advanced solid & central nervous system tumors, including patients who have not previously received BRAF targeted treatment. FORE8394 is a novel, differentiated BRAF inhibitor that uniquely targets Class 1 (V600) and Class 2 alterations, including fusions, and does not induce paradoxical activation of the RAF/MEK/ERK pathway, a limitation of the current standard of care.

Details for the presentation are as follows:

Title: Efficacy of BRAF Inhibitor FORE8394 in BRAF V600+ Patients
Abstract #: 2098
Presentation #: 466P
Presenter: Eric J. Sherman, Memorial Sloan Kettering Cancer Center
Date: Monday, September 12, 2022
Time: 12:00 -13:00 CEST

About FORE8394
FORE8394 is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAFV600 monomers targeted by first-generation RAF inhibitors, but also disrupts constitutively active dimeric BRAF class II mutants, fusions, splice variants and others. Unlike first-generation RAF inhibitors, FORE8394 does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a "paradox breaker," FORE8394 could therefore treat acquired resistance to current RAF inhibitors, and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors

On August 9, 2022 ADC Therapeutics SA (NYSE: ADCT) reported financial results for the second quarter ended June 30, 2022 and provided business updates (Press release, ADC Therapeutics, AUG 9, 2022, View Source [SID1234617957]).

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"The ZYNLONTA launch is advancing steadily as we continue to increase awareness and advocacy. There is significant opportunity ahead and we have a focused plan in place to achieve continued growth in the coming quarters," commented Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Our pipeline of hematology and solid tumor programs is progressing well with impressive Cami Phase 2 data in Hodgkin lymphoma presented at the EHA (Free EHA Whitepaper) Congress in June. Our recent license agreement with Sobi in Europe gives us worldwide access for ZYNLONTA. We have a strong cash runway extending into early 2025 which makes us well-positioned to execute on our key objectives."

Recent Highlights and Developments

Corporate Update

Announced an exclusive license agreement with Swedish Orphan Biovitrum AB (Sobi) for the development and commercialization of ZYNLONTA for all hematologic and solid tumor indications outside of the United States, greater China, Singapore and Japan.
Appointed David Gilman as Chief Business & Strategy Officer.
Elected veteran oncology drug developer Jean-Pierre Bizzari, MD, and CEO Ameet Mallik to the Company’s Board of Directors.
Hematology Franchise

ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA generated net sales of $17.3 million in the second quarter of 2022.
Initiated LOTIS-9, the Phase 2 clinical trial of ZYNLONTA in combination with rituximab in unfit or frail first-line diffuse large B-cell lymphoma (DLBCL) patients.
Initiated LOTIS-7, the Phase 1b clinical trial of ZYNLONTA in combination with other anti-cancer agents.
Terminated LOTIS-6, the Phase 2 clinical trial of ZYNLONTA in patients with relapsed or refractory follicular lymphoma.
The Overland ADCT BioPharma joint venture enrolled the first patient in China in the global LOTIS-5 confirmatory Phase 3 clinical trial of Lonca and rituximab in second-line or later transplant ineligible DLBCL patients.
Overland ADCT Biopharma completed enrollment of the single-agent bridging study in third-line+ DLBCL, which forms the basis for submission of a marketing application in China.
Cami (camidanlumab tesirine) in Hodgkin lymphoma

Released results from the Phase 2 Hodgkin lymphoma (HL) registrational trial at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress in June. These results showed an overall response rate (ORR) of 70%, a complete response (CR) rate of 33% and a median duration of response (DOR) of 13.7 months. Safety data confirmed the manageable tolerability of Cami in these patients.
Solid Tumor Franchise

ADCT-601 (targeting AXL)

Initiated the Phase 1b combination trial in multiple solid tumors.
Upcoming Expected Milestones

Hematology Franchise

ZYNLONTA

Present LOTIS-5 safety lead-in data at an upcoming medical meeting in 2H 2022
Receive a regulatory decision for third-line DLBCL from the Committee for Medicinal Products for Human Use (CHMP), a committee of the European Medicines Agency (EMA), by 1Q 2023
Cami

Meet with the U.S. Food and Drug Administration (FDA) for HL pre-Biologics License Application (BLA) meeting in September 2022
Complete BLA submission for HL to the FDA in 2H 2023
Solid Tumor Franchise

Cami (targeting CD25)

Preliminary results of safety and clinical activity are anticipated in 2023 for the Phase 1b solid tumor trial of Cami in combination with pembrolizumab
ADCT-901 (targeting KAAG1)

Preliminary results of safety and tumor response for the Phase 1 dose escalation trial in multiple solid tumors are anticipated in 2023
Second Quarter Financial Results

Cash and Cash Equivalents

Cash and cash equivalents were $376.8 million as of June 30, 2022, compared to $466.5 million as of December 31, 2021.

Product Revenue

Product revenue (net) was $17.3 million for the quarter, compared to $3.8 million for the same quarter in 2021. Net revenues are for U.S. sales of ZYNLONTA, which received accelerated approval from the FDA on April 23, 2021.

Cost of product sales

Cost of product sales was $2.3 million for the quarter, compared to $0.1 million for the same quarter in 2021, an increase of $2.1 million associated with $1.9 million of impairment charges primarily related to the manufacturing of antibodies that was not within the Company’s specifications. The specification issues did not, and are not expected to, impact the Company’s ability to supply commercial product. In addition, cost of product sales increased due to a full second quarter of sales activity in 2022 as compared to the same period in 2021 due to the commencement of ZYNLONTA sales in May 2021.

Research and Development (R&D) Expenses

R&D expenses were $48.5 million for the quarter ended June 30, 2022, compared to $39.5 million for the same quarter in 2021. As a result of FDA approval of ZYNLONTA in April 2021, the Company reversed $6.8 million of previously recorded impairment charges during the three months ended June 30, 2021, relating to inventory costs incurred for the manufacture of product prior to FDA approval. In addition, R&D expenses increased due to clinical activities to expand ZYNLONTA’s potential market opportunities in earlier lines of therapy and advance the Company’s portfolio of solid tumor programs.

Selling and Marketing (S&M) Expenses

S&M expenses were $17.7 million for the quarter ended June 30, 2022, as compared to $15.2 million for the same quarter in 2021. The increase in S&M expenses is related to the ongoing launch of ZYNLONTA.

G&A Expenses

G&A expenses were $18.2 million for the quarter ended June 30, 2022, compared to $19.4 million for the same quarter in 2021. G&A expenses decreased primarily due to lower share-based compensation expense.

Net Loss and Adjusted Net Loss

Net loss was $64.4 million, or a net loss of $0.84 per basic and diluted share, for the quarter ended June 30, 2022. This compares to a net loss of $72.6 million, or a net loss of $0.95 per basic and diluted share, for the same quarter in 2021. The decrease in net loss for the quarter ended June 30, 2022, as compared to the same period in 2021, was primarily due to higher product revenue, partially offset by the increase in cost of product sales, R&D and S&M expenses. In addition, net loss decreased for the second quarter of 2022 as a result of income arising from changes in the fair value of derivatives associated with our Deerfield Facility Agreement, partially offset by higher interest expense associated with the deferred obligation with Healthcare Royalty Partners.

Adjusted net loss was $56.3 million, or an adjusted net loss of $0.73 per basic and diluted share, for the quarter ended June 30, 2022. This compares to $53.7 million, or an adjusted net loss of $0.70 per basic and diluted share, for the same quarter in 2021.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast to discuss second quarter 2022 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at www.ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On August 9, 2022 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, reported a peer-reviewed paper published in Nature Genetics using the GeoMx Human Whole Transcriptome Atlas (WTA) to construct a high-resolution molecular landscape of pancreatic cancer (Press release, NanoString Technologies, AUG 9, 2022, View Source [SID1234617956]). This paper, along with a tissue image generated using the GeoMx Digital Spatial Profiler (DSP), is featured on the cover of the August 2022 edition of Nature Genetics.

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The paper, "Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment," was authored by a team led by William L. Hwang, M.D., Ph.D., Assistant Professor at Harvard Medical School and Clinician-Investigator in the Center for Systems Biology, Center for Cancer Research and Department of Radiation Oncology at Massachusetts General Hospital.

Since pancreatic cancer is one of the most challenging malignancies to treat with standard approaches, the research team sought to advance precision oncology strategies by understanding the molecular landscape of the multicellular subtypes and spatial communities of this cancer, including how they are remodeled after treatment.

The researchers used single-nucleus RNA sequencing (snRNA-seq) and digital spatial profiling with the GeoMx WTA to profile the tumors from a cohort of patients before or after neoadjuvant intervention. The snRNA-seq cell type signatures were used to deconvolve the GeoMx spatial profiles, demonstrating the complementarity of the two platforms. Together, the platforms demonstrated that malignant cells following different cellular programs (basal-like vs. classical-like) cluster in distinct immune niches within a tumor. The spatially-resolved transcriptomics analysis supported the hypothesis that basal-like malignant cell programs and classical-like programs drive different degrees of immune infiltration with distinct immune cell compositions and suggests that therapeutic strategies may be more effective if differentially targeted for these specific phenotypes.

"Since resistance to cytotoxic therapy is pervasive, there is a critical need to elucidate clinically-relevant gene expression programs and spatial relationships among malignant and stromal cells in the tumor microenvironment, particularly in residual disease," said Hwang. "GeoMx spatial technology was critical in achieving this research objective because it allowed us to map our single-nucleus gene expression programs onto the tumor architecture with high fidelity (whole transcriptome) and in a cell-type specific manner (morphology antibody-based segmentation) and was optimized for FFPE samples, which is the specimen format that is most commonly available in the clinic. This unique combination of technological features enabled us to refine our understanding of the molecular taxonomy and spatial organization of PDAC that will ultimately advance precision oncology for this deadly disease."

The high-resolution molecular framework sheds light on pancreatic cancer’s inter-and intra-tumoral diversity, spatial organization into discrete communities, treatment-associated remodeling, and clinically relevant prognostication. With these findings, researchers can harness this information to augment precision oncology efforts in pancreatic cancer and drive significant breakthroughs in oncology research.

On August 9, 2022 ChemoCentryx, Inc., (Nasdaq: CCXI), reported the cancellation of its second quarter 2022 financial results conference call scheduled for Tuesday, August 9, 2022, at 5:00 p.m. ET (Press release, ChemoCentryx, AUG 9, 2022, View Source [SID1234617955]). The call is being cancelled due to the August 4, 2022, announcement that Amgen and ChemoCentryx, Inc. signed a definitive agreement pursuant to which Amgen would acquire ChemoCentryx.

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ChemoCentryx filed its Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, on August 8, 2022.