On May 18, 2023 FibroGen, Inc. (NASDAQ: FGEN) and its subsidiary, FibroGen (China) Medical Technology Development Co., Ltd. reported positive topline data from Company’s Phase 3 clinical study of roxadustat for treatment of anemia in patients receiving concurrent chemotherapy treatment for non-myeloid malignancies in China (Press release, FibroGen, MAY 18, 2023, View Source [SID1234631844]).

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Roxadustat (爱瑞卓) demonstrated non-inferiority compared to recombinant erythropoietin alfa (SEPO) on the primary endpoint of change in hemoglobin (Hb) level from baseline to the average level during weeks 9-13.

In the preliminary safety analysis, the adverse event profile of roxadustat was generally consistent with previous findings and supportive of a positive benefit risk in this patient population.

"Roxadustat is a promising potential new oral drug for treating chemotherapy-induced anemia, which complicates the treatment of many cancer patients," said Mark D. Eisner, MD, MPH, Chief Medical Officer, FibroGen. "Chemotherapy-induced anemia remains an unmet medical need in China, and we believe that roxadustat has potential to improve the lives of these patients."

A total of one-hundred fifty-nine (159) patients with non-myeloid malignancy (solid tumor) with a baseline hemoglobin level at or below 10 g/dL were enrolled into this Phase 3, randomized, open-label, active-controlled study investigating the efficacy and safety of roxadustat for treatment of chemotherapy-induced anemia (CIA). Patients were randomly assigned roxadustat or erythropoietin alfa three times per week (TIW), during a treatment period of 12 weeks, with an additional 4-week follow-up period. The primary endpoint of the study was change in hemoglobin level from baseline to the average level during weeks 9-13. For more information regarding this study, please visit www.clinicaltrials.gov (NCT05301517).

Detailed results from the study will be submitted for presentation at an upcoming medical conference.

This Phase 3 study is sponsored and conducted by FibroGen and is part of the collaboration with AstraZeneca. FibroGen will work with AstraZeneca and the China Health Authority to file the supplemental New Drug Application.

About Chemotherapy-Induced Anemia
Although chemotherapy-induced anemia is one of the most common side effects of chemotherapy, it is often not recognized and is frequently undertreated. CIA can adversely affect long-term patient outcomes, as anemia limits both quality of life and efficacy of chemotherapy treatment. The incidence and severity of CIA depends on a variety of factors. This includes the type of cancer and the treatment, including the type of chemotherapy, schedule, and intensity of therapy. It also depends on whether the patient has received prior myelosuppressive chemotherapy, radiation therapy, or both. An estimated 30% to 90% of cancer patients receiving chemotherapy develop anemia; and in China the figure approaches 80%1. Approximately 650,000 cancer patients undergo chemotherapy every year in the United States. In China, over 3 million cancer patients undergo chemotherapy2.

About Roxadustat
Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) in China.

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca to regulatory authorities across the globe, and are currently under review. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, and other markets not licensed to Astellas.

On May 18, 2023 Evogene presented its investor presentation (Presentation, Evogene, MAY 18, 2023, View Source [SID1234631843]).

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On May 18, 2023 Bio-Techne Corporation (NASDAQ: TECH) reported that Exosome Diagnostics, a Bio-Techne brand, has reported interim results from a previously published prospective, randomized study of more than 1,000 patients aimed at evaluating the clinical utility of the ExoDx Prostate Test over a 5-year follow-up period (Press release, Bio-Techne, MAY 18, 2023, View Source [SID1234631840]). This study adds to the body of published evidence on the ExoDx Prostate Test. The results came out in a peer-reviewed paper published today in Prostate Cancer and Prostatic Diseases.

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In the ongoing study, researchers are assessing clinical outcomes for 1,049 men age 50 or older with a PSA in the gray zone. At the halfway point of this 5-year study, researchers reported that patients identified as low risk by the ExoDx Prostate Test received fewer biopsies, significantly deferred the time to their first biopsy, and were significantly less likely to be diagnosed later with high-grade prostate cancer. Additional biopsies performed over the 2.5 years found additional cancer in both study arms, but the ExoDx Prostate Test arm still found more high-grade prostate cancer (≥GG2) than the standard of care arm.

Prostate cancer is the most common type of cancer found in men, accounting for more than a quarter of all newly diagnosed cancer cases. Early detection is linked to improved survival rates, but typical screening recommendations — such as digital rectal exams or testing for the prostate specific antigen (PSA) biomarker — do not give the full picture. Additional datapoints can aid in risk assessment and identify cases of high-grade prostate cancer that require aggressive treatment.

The ExoDx Prostate Test analyzes key molecular information from exosomes, vesicles that contain full genomic material, and are naturally released from cells and accessible in urine samples. The ExoDx Prostate Test result is independent of the typical data collected in standard of care protocols, offering a new dimension of information to help shed light on prostate cancer risk. The ExoDx Prostate Test was designed to stratify patients with a likelihood of low-grade prostate cancer from those at risk of high-grade prostate cancer. This more accurate assessment enables physicians to understand whether a biopsy procedure is necessary for patients whose PSA results fall into the uncertain "gray zone" for cancer risk.

"For men at very low risk or very high risk of prostate cancer, the standard of care has worked fairly well for ensuring that patients get what they need. Unfortunately, many men fall somewhere in the middle, and our standard of care protocols are not nearly as clear for those cases," said Ronald F. Tutrone, Jr., MD, Chairman of the William E. Kahlert Endowment for Urological Research, Medical Director of Chesapeake Urology Research Associates, and lead author of the paper. "We are excited about the potential for a new approach like the ExoDx Prostate Test to provide more actionable information that could help guide care decisions for so many men who are left behind by conventional screening methods."

Johan Skog, Chief Scientific Officer and Vice President at Exosome Diagnostics and senior author of the paper, commented, "We designed the ExoDx Prostate Test to meet the pressing needs in prostate cancer healthcare today and we are delighted about its performance so far in this important study. As a noninvasive test independent of clinical standard of care datapoints, it can be used safely and easily as a tool for men to potentially avoid the risks of an invasive biopsy procedure without compromising their health."

Paper cited: Tutrone R et al. ExoDx prostate test as a predictor of outcomes of high-grade prostate cancer – an interim analysis. Prostate Cancer and Prostatic Diseases. View Source

On May 18, 2023 Be Biopharma, Inc. ("Be Bio"), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), reported that it will present preclinical research showing the precise genome engineering of human B cells to express diverse therapeutic proteins using the company’s proprietary platform (Press release, Be Biopharma, MAY 18, 2023, View Source [SID1234631839]). The findings will be presented during an oral session at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 26th Annual Meeting at 2:15-2:30 p.m. PST with additional data in poster presentation 1453 on Friday, May 19th from 12:00-2:00 p.m. PST.

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Plasma cells are terminally differentiated B cells, which can live for decades1 and have the capacity to secrete extremely high levels of protein2 making them attractive for the sustained delivery of biologics to treat a wide range of diseases. However, it has historically been challenging to genetically engineer B cells efficiently, precisely, and in a manner that could produce proteins at therapeutic levels over long durations. Leveraging the convergence of advanced gene editing, deep insights into B cell biology and cell therapy technologies, Be Bio has designed a versatile CRISPR/Cas9 engineering platform capable of delivering a gene of interest via homology-directed repair (HDR) to produce stable BeCMs.

"In a short two years, Be Bio has validated key concepts of our B cell medicine platform including editing precision and efficiency, reproducible engraftment, and durable functional protein expression with the goal of creating a new class of cellular medicines with broad therapeutic utility," said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. "B cell medicines have the potential to transform the lives of patients – they can be redosed when required, delivered autologously and allogeneically, and can be administered without preconditioning – offering distinct advantages over other advanced therapies."

Be Bio Platform Attributes

Engineering Precision and Efficiency:
Depending on the desired therapeutic protein expression level, the platform can target gene insertions to safe harbor sites as well as sites transcriptionally active in B cells. Across transgenes, targeting a transcriptionally active B cell site can enable up to a tenfold increase in protein secretion compared to insertion at the CCR5 safe harbor site. In addition, precisely targeted integration significantly reduces the risk of random gene insertion.

Using optimized cell culture and engineering conditions, the platform achieves gene knockouts with greater than 90% efficiency, stable gene insertion via precise HDR with up to 60% efficiency as measured by digital droplet PCR, and multiplexed expression of two genes with efficiencies above 20% as measured by flow cytometry.

Durable and Functional Protein Expression:
We observed the robustness of the platform through the expression of multiple therapeutic proteins such as Factor IX (FIX) for hemophilia B, acid sphingomyelinase (ASM) for Niemann-Pick Diseases (NPD) and an anti-CD19/CD3 bispecific T cell engager for acute lymphoblastic leukemia (ALL).

In each of two donors, FIX was detected in mouse plasma and lasted for greater than 18 weeks post BeCM transfer demonstrating persistence. In a separate experiment, BeCM-secreted ASM corrected the disease phenotype in NPD (SMPD1) gene knock-out cells.

In addition, in vitro and in vivo anti-tumor activity was observed. Potent in vitro anti-tumor activity was shown when supernatant from bispecific T cell engager-producing BeCMs directed primary human T cells to kill Raji tumor cells (CD19+). In a study conducted by Be Bio’s scientific co-founders and collaborators from the Seattle Children’s Research Institute, engineered B cells produced bispecific T cell engagers in vivo that mediated T cell activation and showed anti-tumor efficacy in a patient-derived xenograft mouse model3.

Rapid Screening:
To supplement adeno-associated virus (AAV) vector-mediated HDR, a rapid plasmid-based screening protocol was developed. The plasmid-based platform efficiently identifies the appropriate parameters for the secretion of a given protein of interest in primary B cells enabling rapid development from idea to prototype. The screening protocol assesses gene and protein design parameters for optimal transgene expression levels.

Engraftment without Preconditioning:
Rapid homing (within one day) and engraftment without preconditioning were shown in two models. In immunodeficient (NOG-hIL6) mice, BeCMs engrafted and persisted for greater than 100 days. In non-human primates with intact immune systems, BeCMs administered by intravenous infusion homed to and engrafted in the bone marrow and spleen.

These fundamental platform attributes overcome historical challenges for scalable and effective B cell engineering. The platform has the potential to transform the power of B cells into the development of autologous and allogeneic B cell medicines and unlock a pipeline of product candidates for broad and meaningful therapeutic utility in rare disease, cancer and beyond.

About B Cells – A New Class of Cellular Medicines

Imagine what could "Be?" In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BeCMs). BeCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BeCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.

On May 18, 2023 Athersys, Inc. (NASDAQ: ATHX), a regenerative medicine company developing MultiStem (invimestrocel) cell therapy for critical care indications, reported on Monday, May 15th financial results for the three months ended March 31, 2023 and provided a business update (Press release, Athersys, MAY 18, 2023, View Source [SID1234631837]).

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First Quarter 2023 and Recent Corporate and Operational Highlights:

•Continued reducing expenses to conserve cash and heightened focus on MASTERS-2 trial, thereby making Athersys more attractive to potential financial and strategic partners
•Maintained operating expenses below $2.5 million per month
•Raised $3.7 million through a registered direct offering with institutional investors
•Appointed biotechnology and pharmaceutical executive Joseph Nolan to the Board of Directors
•Participated in Request for Proposal (RFP) process with the Biomedical Advanced Research and Development Authority (BARDA) for a proposed clinical trial with MultiStem for acute respiratory distress syndrome (ARDS) and other COVID-19 co-morbidities
•Completed DSMB review of cohort 1 & 2 of MATRICS trauma trial using both cell factory and bioreactor manufactured clinical product
•Awarded a U.S. patent for the novel SIFU cryogenic storage system, the Company’s user-friendly system to improve storage and handling of cryogenic products in hospital settings

MASTERS-2

•Amended the clinical trial protocol reflecting modifications proposed during a Type B meeting with the U.S. FDA that best reflect the potential benefits of MultiStem in treating acute, moderate-to-severe ischemic stroke; protocol modifications include:
◦Primary endpoint assessed by shift analysis in modified Rankin Scale (mRS) score was changed to Day 365, from Day 90 previously
◦Shift analysis in mRS score at Day 90 is retained as a key secondary endpoint
◦Eligibility caps on concomitant reperfusion therapy (e.g., tPA, MR or tPA+MR) were removed to ensure the study population reflects the population eligible for this therapy
◦Added the option to conduct an interim analysis for powering to confirm 300 patient sample size is adequate to achieve statistical significance with new primary endpoint
Medical Affairs
•Athersys executives participated in several industry conferences to build awareness of Athersys and share clinical and manufacturing progress achieved with MultiStem , including:
◦Advanced Therapies Week presented by Phacilitate
◦2nd Allogeneic Cell Therapies Summit Europe
◦International Stroke Conference 2023
◦BioProcess International US West
◦The American Society for Neural Therapy and Repair Annual Conference
◦Cellular Therapies and Transfusion Medicine in Trauma and Critical Care Conference

Management Commentary

"We entered 2023 with greater clarity and confidence on our path forward with MultiStem having largely completed a significant restructuring in the second half of last year that reduced our operating expenses below $2.5 million per month. In addition, achieving a successful Type B meeting with the FDA on proposed MASTERS-2 trial modifications will now more appropriately represent the regenerative benefits of MultiStem over a longer period and reflect changes we’ve observed in ischemic stroke standard of care. We’ve also made meaningful progress with trial enrollment and advanced conversations with multiple parties exploring business development opportunities with MultiStem as well as our animal health franchise and SIFU," said Dan Camardo, Chief Executive Officer of Athersys. "We have more work to do, but I’m encouraged by the progress we’ve made."

First Quarter Results

There was no revenue for the first quarter of 2023 compared with $2.9 million for the first quarter of 2022, which included the delivery of services under the arrangement with Healios. As of September 30, 2022, services under this arrangement were largely complete and were limited to close-out activities.
Research and development expenses were $4.5 million for the first quarter of 2023 compared with $20.9 million for the comparable period in 2022. The decrease reflects our restructuring plan which resulted in reduced clinical trial expenses which includes personnel, manufacturing and other costs.
General and administrative expenses were $2.8 million for the first quarter of 2023 compared with $4.1 million for the comparable period in 2022, with the decrease primarily due to the restructuring. The Company expects further decreases in general and administrative expenses.
Net loss for the first quarter of 2023 was $7.8 million, or $0.43 per share, compared with a net loss of $22.2 million, or $2.27 per share, for the comparable period in 2022.
Cash and cash equivalents were $3.1 million as of March 31, 2023 compared with $9.0 million as of December 31, 2022.

About MultiStem
MultiStem (invimestrocel) cell therapy is a patented regenerative medicine product in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors in response to signals of inflammation and tissue damage. MultiStem therapy’s potential for multidimensional therapeutic impact distinguishes it from traditional biopharmaceutical therapies focused on a single mechanism of benefit. The therapy represents a unique "off-the-shelf" stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. Based upon its efficacy profile, its novel mechanisms of action, and a favorable and consistent tolerability demonstrated in clinical studies, we believe that MultiStem therapy could provide a meaningful benefit to patients, including those suffering from serious diseases and conditions with unmet medical need.