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Omeros Corporation Announces Availability on Its Website of Materials Accompanying Presentations of OMS906 Data at the 2023 European Hematology Association Congress

On June 12, 2023 Omeros Corporation (Nasdaq: OMER) reported that the slides presented yesterday in the "late-breaker" session at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Frankfurt, Germany are now available on Omeros’ website (Press release, Omeros, JUN 12, 2023, View Source [SID1234632685]). The presentation, which details data from a pre-specified interim analysis from the ongoing Phase 1b clinical trial of Omeros’ lead MASP-3 inhibitor OMS906 in complement-inhibitor-naïve adults with paroxysmal nocturnal hemoglobinuria (PNH), was identified by EHA (Free EHA Whitepaper)’s Scientific Program Committee as one of the top five late-breaking submissions and selected for oral presentation. The presentation, entitled OMS906, A mannan-binding lectin-associated serine protease-3 (MASP-3) Inhibitor, Normalizes Hemoglobin Levels in Treatment-naïve PNH Patients: Interim Data from a Proof-of-Concept Clinical Trial, was delivered to a large audience by Jens Panse, MD, Senior Physician and Deputy Director of the Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, and Managing Medical Director of the Center for Integrated Oncology, Aachen, Germany.

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Also available on Omeros’ website is a second presentation at EHA (Free EHA Whitepaper) – Alternative Pathway MASP-3 Inhibitor OMS906: Results from a First-in-Man Phase 1 Study in Healthy Subjects and Study Design of Two Ongoing Clinical Trials in Patients with PNH – by Morag Griffin, MBChB, FRCPath, Consultant in Haematology of St. James University Teaching Hospital, Leeds, United Kingdom. This poster presentation describes findings from a single-ascending dose study evaluating OMS906 safety, pharmacokinetics and pharmacodynamics in healthy subjects.

About PNH

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening acquired disorder that causes production of red blood cells lacking certain surface proteins (CD55 and CD59), making them vulnerable to destruction by the complement system. This leads to intravascular hemolysis (destruction of red blood cells within blood vessels) and extravascular hemolysis (when damaged red blood cells are removed by macrophages in the spleen or liver). Left untreated, PNH is associated with debilitating anemia, a high risk of thrombosis, fatigue, and a severely reduced survival rate. There remains a significant unmet need for PNH therapies, as a large proportion of patients treated with C5 inhibitors continue to experience hemolysis and approximately one third of them still require red blood cell transfusions.

About OMS906

OMS906 is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the key activator of the complement system’s alternative pathway. The complement system plays a central role in inflammation and becomes activated as a result of tissue damage or microbial infection. Responsible for the conversion of pro-complement factor D to complement factor D, MASP-3 is believed to be the premier target in the alternative pathway. MASP-3 has the lowest native circulating level and low relative clearance compared to the other alternative pathway proteins and, unlike C5 and C3 blockers, MASP-3 inhibition leaves intact the lytic arm of the classical pathway, important for fighting infection. Also, unlike other components of the alternative pathway, MASP-3 is believed not to be an acute phase reactant, which could provide a significant advantage to MASP-3 inhibitors, like OMS906, over other alternative pathway inhibitors. MASP-3 inhibitors are thought to have preventive or therapeutic effects across a broad range of diseases including PNH, hemolytic uremic syndrome (HUS), atypical HUS, traumatic brain injury, arthritis, wet age-related macular degeneration, ischemia-reperfusion injury, transplant-related complications and other immune-related disorders. Through its growing and exclusive intellectual property position, Omeros controls the use of MASP-3 inhibitors across a wide range of alternative pathway-related and other diseases and disorders.

Ferring Pharmaceuticals Receives U.S. FDA Approval of Drug Substance Manufacturing Scale-up Process for Gene Therapy ADSTILADRIN® (nadofaragene firadenovec-vncg)

On June 12, 2023 Ferring Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) approved a Prior-Approval Supplement (PAS) to the Biologics License Application (BLA) for the novel intravesical gene-therapy ADSTILADRIN (nadofaragene firadenovec-vncg), enabling the Company to scale-up its drug substance manufacturing process at FinVector Oy located in Kuopio, Finland (Press release, Ferring Pharmaceuticals, JUN 12, 2023, View Source [SID1234632684]). Supplies from the scale-up process manufactured at FinVector’s FDA-approved facility will be available as part of the planned product launch.

"The FDA approval of this supplement is an important step in our manufacturing scale-up which highlights our continued commitment to bring ADSTILADRIN to the community and in helping patients who are suffering from non-muscle invasive bladder cancer," said Brent Ragans, U.S. President, Ferring Pharmaceuticals.

In May 2022, FinVector started construction of a new facility in Kuopio, Finland which will be one of the world’s largest viral vector manufacturing sites. FinVector is a world leader in development and manufacturing of viral-based gene therapy products. A separate facility dedicated to ADSTILADRIN is under construction within Ferring’s FDA-approved manufacturing site at the Parsippany, New Jersey campus and will add near-term drug product capacity.

"Viral-based gene therapies like ADSTILADRIN have great potential for the treatment of severe diseases, including cancers where there is a high unmet patient need," said Giuseppe Carloni, Board Member, FinVector. "Our long-established depth of expertise positions FinVector to remain at the forefront of pioneering the development and manufacture of new precision medicines."

ADSTILADRIN was approved by the FDA in December 2022 for the treatment of adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. As the first and only FDA-approved intravesical gene therapy for these patients, ADSTILADRIN provides a potentially transformational alternative to invasive bladder removal surgery.

Ferring remains on track to start making ADSTILADRIN initially available as part of a focused rollout in the United States in the second half of 2023, with supplies increasing in 2024.

About ADSTILADRIN
ADSTILADRIN (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).1

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 20223, 75% of which present as NMIBC.4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.2 Current treatment options for BCG-unresponsive patients are very limited, and often result in a highly invasive life-changing procedure of radical cystectomy (complete removal of the bladder).5

INDICATION

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

IDEAYA Announces Selection of IDE397 Phase 2 Monotherapy Expansion Dose For Global Enrollment Targeting High Priority MTAP-Deletion Solid Tumor Types

On June 12, 2023 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported selection of a monotherapy expansion dose for the Phase 2 clinical trial evaluating IDE397 in patients having solid tumors with MTAP deletion (Press release, Ideaya Biosciences, JUN 12, 2023, View Source [SID1234632678]).

"We have selected a IDE397 Phase 2 monotherapy expansion dose for evaluation in our high-priority solid tumor types with MTAP deletion, including NSCLC, bladder cancer and gastroesophageal cancer. We are in the early stages of enrollment into our global Phase 2 clinical trial monotherapy expansion and have clinical objectives to further define IDE397’s monotherapy efficacy in our high priority solid tumor types and to address contribution of components for clinical combinations," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A). IDEAYA is clinically evaluating IDE397 as monotherapy in a Phase 1/2 clinical trial in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, with ongoing enrollment into the global Phase 2 clinical trial.

IDEAYA is focusing monotherapy expansion cohorts in high-priority tumor types with MTAP deletion, including NSCLC, bladder cancer and gastricesophageal cancer. MTAP deletion is estimated to occur in ~16% of non-small cell lung cancer (NSCLC), ~30% of bladder cancer and ~15% to ~25% of gastricesophageal cancer. These monotherapy indications are being prioritized based on preliminary clinical efficacy and preclinical data demonstrating in vivo efficacy in relevant patient- and/or cell-derived xenograft models and observed endogenous pathway suppression in MTAP deleted tumors. These data were presented at the 2023 Annual Meeting of the American Association of Cancer Research (AACR 2023).

The company observed tumor shrinkage in multiple patients treated with IDE397 monotherapy in IDEAYA’s high-priority MTAP-deletion solid tumor types, including a pre-treated patient that had an observed partial response (PR) by RECIST 1.1 (~40% tumor reduction) at the first post-baseline scan.

IDEAYA is collaborating with Amgen to clinically evaluate IDE397 in combination with AMG 193 in patients having solid tumors with MTAP deletion. AMG 193 is the Amgen investigational MTA- cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. The clinical evaluation of IDE397 with AMG 193 represents a novel and potential first-in-class synthetic lethality combination. Targeting two mechanistically distinct nodes of the MTAP methylation pathway – MAT2A and PRMT5 provides a synergistic approach for targeting MTAP-null tumors.

In May 2023, IDEAYA reported clearance of the Amgen-sponsored Investigational New Drug (IND) application and U.S. FDA authorization to proceed with the IDE397 / AMG 193 Phase 1/2 clinical trial. The Phase 1/2 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with AMG 193.

IDEAYA and Amgen co-presented preclinical data at AACR (Free AACR Whitepaper) 2023 demonstrating deep and durable anti-tumor efficacy for the IDE397 and AMG 193 combination in a NSCLC MTAP-null CDX model. These data showed complete responses following approximately 30 days of combination treatment at doses below the maximally efficacious preclinical dose for each compound, which were durable from approximately study-day 40 to study-day 100. The IDE397 and AMG 193 combination was well tolerated, with no observed body weight loss through the approximate 30 days of combination treatment in these models. Additionally, the results of gene expression analysis of hallmark pathways, alternative splicing analysis and retained intron analysis collectively demonstrated that combined pharmacological inhibition of MAT2A and PRMT5 deepens the biological response through maximal pathway suppression. The enhanced combination effect was observed selectively in MTAP-deleted models.

Pursuant to the mutually non-exclusive CTCSA, Amgen is the sponsor of the IDE397 and AMG 193 combination clinical trial and each of IDEAYA and Amgen will supply their respective compounds, IDE397 and AMG 193. Each party will pay fifty percent (50%) of the external third-party costs for conducting the clinical trial and be wholly responsible for their respective own internal costs and expenses in support of the clinical trial. The companies will jointly own clinical data and all intellectual property, if any, relating to the combined use of IDE397 and AMG 193 from the clinical trial. Each party retains commercial rights to its respective compounds, including with respect to use as a monotherapy or combination agent. The companies have formed a joint oversight committee responsible for coordinating all regulatory and other activities in support of the clinical trial.

Actinium Announces Positive Pivotal Phase 3 SIERRA Trial Results in an Oral Presentation at the EHA 2023 Congress

On June 12, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported positive SIERRA trial results in an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress (EHA) (Free EHA Whitepaper) in Frankfurt, Germany on June 10 (Press release, Actinium Pharmaceuticals, JUN 12, 2023, View Source [SID1234632675]). The abstract included data from Actinium’s SIERRA controlled phase 3 study comparing the efficacy of Iomab-B based conditioning, a first-in-class targeted radiotherapy, versus physician’s choice of conventional care in older, relapsed/refractory acute myeloid leukemia (r/r AML) with active disease.

"We are honored to have been accepted for an oral presentation at EHA (Free EHA Whitepaper)," said Sandesh Seth, Chairman and Chief Executive Officer. "This presentation is the third of four orals at prestigious medical conferences globally in 2023, including TCT, EBMT and SNMMI, reflecting the paradigm changing potential of Iomab-B in facilitating transplants for patients who are currently not considered for transplant."

Details of the EHA (Free EHA Whitepaper) presentation:

Presentation Title: SIERRA trial results with a targeted radiotherapy, Iomab-B, a myeloablative conditioning with reduced intensity tolerability yields high CR, long term survival in HSCT ineligible active r/r AML
Presenting Author: Dr. Boglarka Gyurkocza
Session Type/Title: Oral / SCT Clinical
Presentation ID: S248 (View Source)
Date and Time: June 10, 11:30am – 12:45pm CET

In patients over 55 with active r/r AML, Iomab-B was able to safely deliver myeloablative doses of targeted radiation to bone marrow. Iomab-B based conditioning with bone marrow transplant (BMT) resulted in rapid engraftment and high initial complete remission/complete remission with incomplete platelet recovery rates, a favorable toxicity profile and resulted in statistically significant improvement in the pre-specified primary endpoint of durable complete remission (dCR). The majority of patients who achieved dCR are long term survivors, in whom OS and EFS was significant. Iomab-B based conditioning was well-tolerated and provided access to HSCT with curative potential in a vulnerable patient population traditionally not considered eligible for HSCT.

Mustang Bio Announces Updated Results from Waldenstrom Macroglobulinemia Cohort of Ongoing Phase 1/2 Clinical Trial of MB-106, CD20-Targeted Autologous CAR T Therapy

On June 12, 2023 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, reported that updated data from the ongoing Phase 1/2 clinical trial of MB-106, a CD20-targeted, autologous CAR T cell therapy, show a favorable safety and efficacy profile in patients with Waldenstrom macroglobulinemia ("WM"), a rare form of blood cancer (Press release, Mustang Bio, JUN 12, 2023, View Source [SID1234632674]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch") to treat patients with relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHLs") and chronic lymphocytic leukemia ("CLL").

The updated results from the single-institution Phase 1/2 clinical trial were presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress ("EHA2023") by Mazyar Shadman, M.D., M.P.H., Associate Professor and physician at Fred Hutch and University of Washington.

"As we continue to evaluate MB-106 in this single-institution study, we’re encouraged by its potential to become an outpatient treatment option for WM and other B-cell malignancies, including indolent and aggressive non-Hodgkin lymphomas," said Dr. Shadman. "We have observed ongoing responses to MB-106 with improvements in the quality of response over time, along with a favorable safety profile."

All six patients in the study were previously treated with Bruton’s tyrosine kinase inhibitors ("BTKi"), and their disease continued to progress while on BTKi’s. Overall, 83% (5/6) of the patients treated with MB-106 responded to treatment, including 2 complete responses, 1 very good partial response, 1 partial response, and 1 minor response. In addition, 1 patient experienced stable disease. One of the patients who achieved a complete response has remained in remission for 22 months, with an immunoglobulin M (IgM) level that decreased rapidly to the normal range after treatment with MB-106 and has remained normal since. No patient has started additional anti-WM treatment after being treated with MB-106. From a safety perspective, cytokine release syndrome (CRS) occurred in five patients: two patients with grade 1 and three patients with grade 2. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). No grade 3 or 4 CRS or grade 2, 3 or 4 ICANS has been observed.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, commented, "MB-106 has the potential to fill a significant unmet need, as there are currently no CAR T treatments for WM approved by the U.S. Food and Drug Administration ("FDA"). The MB-106 data from the Phase 1/2 clinical trial taking place at Fred Hutch continue to be encouraging for WM and other B-NHLs. The positive data from this study and the FDA Orphan Drug Designation MB-106 received for WM support the treatment of patients with WM in the Phase 1 portion of our multicenter Phase 1/2 clinical trial which is underway and also support a fast-to-market Phase 2 strategy for this indication. We plan to report initial clinical data from the multicenter program shortly."

For more information on the clinical trials, please visit www.clinicaltrials.gov using the identifier NCT05360238 for the multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch.

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

About MB-106 (CD20-targeted autologous CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody, and MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch is being used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial that is now open to enrollment under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on the trials can be found at View Source using the identifier NCT05360238 for the multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch. Mustang Bio has entered into an Asset Purchase Agreement pursuant to which it has agreed to sell, subject to the satisfaction of certain conditions, its leasehold interest in its cell processing facility and expects to enter into a manufacturing services agreement with the prospective purchaser to provide for the continued production of the MB-106 drug product. For additional information, please refer to the Current Report on Form 8-K filed by Mustang Bio with the U.S. Securities and Exchange Commission ("SEC") on May 22, 2023.