On June 3, 2024 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, will participate in the Jefferies Global Healthcare Conference, being held at the Marriott Marquis, in New York City on June 5-6, 2024 (Press release, TG Therapeutics, JUN 3, 2024, View Source [SID1234644026]). The fireside chat is scheduled to take place on Wednesday, June 5, 2024, at 1:30 PM ET.

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A live webcast of the fireside chat will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source

On June 3, 2024 Sanofi reported data from the IMROZ phase 3 study demonstrated Sarclisa (isatuximab) in combination with standard-of-care bortezomib, lenalidomide and dexamethasone (VRd) followed by Sarclisa-Rd (the IMROZ regimen) significantly reduced the risk of disease progression or death by 40%, compared to VRd followed by Rd in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant (Press release, Sanofi, JUN 3, 2024, View Source [SID1234644025]). IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve PFS and show deep responses in this patient population who often have poor prognoses. The results were shared in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and simultaneously published in the New England Journal of Medicine (NEJM).

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The use of Sarclisa in combination with VRd in transplant-ineligible NDMM is investigational and has not been fully evaluated by any regulatory authority.

Thierry Facon, MD
Professor of Haematology in the Department of Haematology, Lille University Hospital, Lille, France, member of French Academy of Medicine and IMROZ Principal Investigator
"The significant progression-free survival benefit observed with Sarclisa combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma. Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy. The IMROZ results demonstrate the promise of Sarclisa as a backbone to frontline therapy, which may improve long-term outcomes for this incurable disease."

Key Results
IMROZ is a global, randomized, multi-center, open-label study. At the data cut-off of September 26, 2023, through the median follow-up of 59.7 months, the following were observed for Sarclisa-VRd compared to VRd:

Primary endpoint

40% reduction in the risk of disease progression or death for patients treated with Sarclisa-VRd versus VRd (HR 0.596; 98.5% CI: 0.406 to 0.876; p=0.0005). At the median follow-up of 59.7 months, the median PFS with the Sarclisa-VRd combination was not reached versus 54.3 months with VRd.
The estimated PFS at 60 months was 63.2% for patients treated with Sarclisa-VRd versus 45.2% for VRd.
Secondary endpoints

Approximately three-quarters (74.7%) of patients treated with Sarclisa-VRd achieved a complete response (CR) compared to 64.1% of patients taking VRd (OR 1.7; 95% CI: 1.097-2.5; p=0.008).
More than half (55.5%) of patients treated with Sarclisa-VRd achieved MRD negative CR compared to 40.9% of patients taking VRd (OR 1.8; 95% CI: 1.229-2.646; p=0.0013).
MRD was sustained for at least 12 months among nearly half (46.8%) of patients in the Sarclisa-VRd arm compared to less than one-quarter (24.3%) of patients taking VRd (OR 2.7; 95% CI: 1.799-4.141).

At the date of data cut-off, 47.2% of patients (125/263) treated with Sarclisa-VRd and 24.3% of patients (44/181) treated with VRd were still on treatment. The median treatment duration for the Sarclisa-VRd combination was 53.2 months vs. 31.3 months for VRd.

The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa-VRd with no new safety signals observed. Grade ≥3 treatment-emergent adverse events (TEAE) occurred in 91.6% of patients taking Sarclisa-VRd and 84% of patients taking VRd. Treatment-emergent events (TAE) of any grade led to treatment discontinuation in 22.8% of patients taking Sarclisa-VRd and 26% of patients taking VRd.

Peter C. Adamson
Global Development Head, Oncology
"Over the last 20 years, the pace of multiple myeloma research has continued to accelerate, paving the way for treatment advancements with potential to improve outcomes for patients. With our commitment to help lead the way for patients with this disease, we welcomed the IMROZ results presented at ASCO (Free ASCO Whitepaper), and now published in NEJM, which demonstrate Sarclisa’s potential to improve progression-free survival in patients who are newly diagnosed and transplant ineligible. We want to express our deep gratitude to the patients, their families and investigators for their dedication to clinical research."

Advancing Sarclisa in Newly Diagnosed Multiple Myeloma
The US Food and Drug Administration (FDA) accepted for Priority Review the supplemental Biologics License Application (sBLA) for the investigational use of Sarclisa in combination with VRd for the treatment of patients with transplant-ineligible NDMM. A regulatory submission is also under review in the European Union (EU). If approved, Sarclisa would be the first anti-CD38 therapy in combination with standard-of-care VRd in newly diagnosed patients not eligible for transplant, which would be the third indication for Sarclisa in multiple myeloma.

The IMROZ data will also be presented during the plenary scientific session at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress on June 15, selected as one of the top six abstracts to be featured at the congress. There will be two additional oral presentations at EHA (Free EHA Whitepaper) featuring results from phase 3 studies of Sarclisa in NDMM. Additionally, the IMROZ abstract was hand-selected to be included in the 2024 Best of ASCO (Free ASCO Whitepaper) program, held later in the summer of 2024, following the ASCO (Free ASCO Whitepaper) Annual Meeting.

Sanofi’s oncology pipeline and portfolio prioritize areas of high unmet need for difficult-to-treat cancers, including multiple myeloma, which remains an incurable disease despite recent advances in treatment.

About the IMROZ study
The randomized, multi-center, open-label IMROZ phase 3 clinical study enrolled 446 patients with newly diagnosed, transplant-ineligible multiple myeloma (MM) across 21 countries and 104 centers. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for five weeks during first 42-day cycle and once every two weeks in cycles 2 to 4 in combination with subcutaneous bortezomib, oral lenalidomide and intravenous or oral dexamethasone. Then Sarclisa was administered every 2 weeks from cycle 5 to 17 and every 4 weeks in cycles 18+ during 28-day cycles in combination with lenalidomide and dexamethasone at the standard dose, until disease progression, unacceptable safety profile or patient’s decision to stop the study treatment.

The primary endpoint was progression-free survival. Key secondary endpoints include complete response rate, MRD negativity rate for patients with a complete response, very good partial response or better rate, overall survival. Other secondary endpoints are: overall response rate, time to progression, duration of response, time to first response, time to best response, progression-free survival on next line of therapy, progression-free survival by MRD status, sustained MRD negativity greater than or equal to 12 months rate, safety, pharmacokinetic profile, immunogenicity, disease-specific and generic health-related quality of life, disease and treatment-related symptoms, health state utility, and health status.1

The use of Sarclisa in combination with VRd in transplant-ineligible newly diagnosed MM is investigational and has not been fully evaluated by any regulatory authority.

About Sarclisa
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

Based on the ICARIA-MM phase 3 study, Sarclisa is approved in >50 countries, including the US and EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration (FDA).

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

About multiple myeloma
MM is the second most common hematologic malignancy,2 with more than 180,000 new diagnoses of MM worldwide yearly.3 Despite available treatments, MM remains an incurable malignancy with an estimated 52% five-year survival rate for newly diagnosed patients.4 Since MM does not have a cure, most patients will relapse. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

On June 3, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported the presentation of three posters at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL today and online (Press release, Rigel, JUN 3, 2024, View Source [SID1234644024]). Presentations include five-year results from the pivotal cohort of the registrational Phase 2 trial of REZLIDHIA (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML), the safety and efficacy of olutasidenib treatment in a subgroup analyses of elderly patients with R/R mIDH1 AML, and an overview of the ongoing Phase 1b trial of R2891, a potent and selective inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS).

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"Our presentations at ASCO (Free ASCO Whitepaper) build on the strength of REZLIDHIA’s data, reinforcing its important role in the R/R mIDH1 AML treatment landscape. REZLIDHIA continues to demonstrate durable responses and was well tolerated, even in difficult to treat and elderly patients with mIDH1 AML who have more safety concerns," said Raul Rodriguez, Rigel’s president and CEO. "In addition, we are sharing an overview of the ongoing Phase 1b trial of R289 in lower-risk MDS, an area of high unmet need. We believe R289 could potentially provide a new treatment option to patients who have failed other agents."

Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: 6528
Title: Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results from the Phase 2 Pivotal Cohort
Presenter: Jorge E. Cortes, M.D.
Location: McCormick Place South, Exhibit Hall A

An additional two years of data, beyond the results that led to FDA approval of olutasidenib, further demonstrates the durable responses observed with olutasidenib in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. The safety profile was consistent with what was previously reported.
Of 147 efficacy evaluable patients, complete remission (CR) or CR with partial hematologic recovery (CRh) was achieved in 35%. The median time to CR/CRh was 1.9 months and median duration of CR/CRh was 25.3 months, with maximum duration ongoing at 54.6 months. Overall response rate was 48%, with median duration 15.5 months and maximum duration ongoing at 54.6 months. Median overall survival was 11.6 months.
Transfusion independence (for ≥56 days) from red blood cells was achieved in 34 patients (39%) who were dependent at baseline and from platelets was achieved in 28 patients (41%) who were dependent at baseline.
In the 12 patients that were R/R to prior venetoclax, 33% achieved a CR/CRh; median duration of CR/CRh was not reached (ongoing at 50.6 months), and median overall survival was 16.2 months.
Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: 6527
Title: Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.
Location: McCormick Place South, Exhibit Hall A

Olutasidenib was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions, consistent with the population in the pivotal cohort of the Phase 2 registrational trial. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with olutasidenib.
In this subgroup analyses of the registrational Phase 2 trial of olutasidenib in 45 participants aged 75 and older with R/R mIDH1 AML, 31% of patients achieved CR/CRh; median time to CR/CRh was 1.5 months, and median duration of CR/CRh was 25.9 months.
Of the five elderly patients who were R/R to prior venetoclax, four patients (80%) achieved an overall response, including two patients (40%) with CR/CRh.
Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: TPS6591
Title: Phase 1b Trial of IRAK 1/4 Inhibition for Lower-Risk Myelodysplastic Syndrome Refractory/Resistant to Prior Therapies: A Trial in Progress
Presenter: Guillermo Garcia-Manero, M.D.
Location: McCormick Place South, Exhibit Hall A

An overview of the study design of the ongoing Phase 1b trial evaluating R289 in patients with LR-MDS will be presented. The primary endpoint for this trial is safety with key secondary endpoints including preliminary efficacy and evaluation of pharmacokinetic properties.
Enrollment in dose levels 1 (250 mg QD), 2 (500 mg QD), and 3 (750 mg QD) has been completed. Two additional dose levels with twice daily dosing have been added (250 mg BID and 500/250 mg) and the trial is actively recruiting.
To learn more about Rigel and the company’s clinical and commercial hematology and oncology portfolio, visit Booth #11059 during ASCO (Free ASCO Whitepaper).

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.5

About REZLIDHIA
INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

On June 3, 2024 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, reported two oral presentations highlighting promising clinical data from its RP1 and RP2 programs at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31-June 4 in Chicago (Press release, Replimune, JUN 3, 2024, View Source [SID1234644023]).

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"The strength of the RP1 and RP2 data being presented at ASCO (Free ASCO Whitepaper) in two hard-to-treat tumor types further validates the potential of the RPx platform," said Sushil Patel, Ph.D., CEO of Replimune. "In the IGNYTE trial, the investigator-assessed 12-month results show an overall response rate of 32.7% that was highly durable, and the combination provided a favorable safety profile, all consistent with previous data. The data with RP2 as monotherapy and in combination with nivolumab in refractory patients highlights a strong and durable overall response rate of nearly 30 percent in uveal melanoma where treatment options are limited."

Key findings are outlined below.

Oral Presentation: Efficacy and Safety of RP1 Combined with Nivolumab in Patients with anti-PD-1-Failed Melanoma from the IGNYTE Clinical Trial (Session: Melanoma/Skin Cancers; June 3, 2024, 10:57AM CDT; Location: S406; Abstract: 9517)

The data continues to show that the combination of RP1 and nivolumab in anti-PD-1 failed melanoma (n=156) provides deep and durable responses with an "on-target" safety profile with generally transient grade 1/2 adverse events, indicative of systemic immune activation.
Approximately one third of patients experienced a response, with an overall response rate (ORR) by investigator assessment of 32.7%.
In the 94 patients who had primary resistance to their immediate prior anti-PD-1 therapy, the ORR was 34%.
In the 66 patients who progressed on prior anti-PD-1 combined with anti-CTLA-4 therapy, the ORR was 27.3%.
All responses lasted greater than six months from enrollment, with a median duration of response exceeding 36 months.
Clinically meaningful activity was observed across all enrolled subgroups, with over half of patients experiencing either a complete response (CR), partial response (PR) or stable disease (SD).
Primary analysis results by independent central review from the IGNYTE anti-PD-1 failed melanoma cohort are expected later in Q2 2024 with the Company on track to submit a biologics license application (BLA) for RP1 to the U.S. Food and Drug Administration (FDA) in 2H 2024. The Company also has agreed on a protocol for a Phase 3 confirmatory study with the FDA (IGNYTE-3; NCT06264180; poster TPS9603, ASCO (Free ASCO Whitepaper) 2024) and expects to initiate the trial prior to the RP1 BLA in anti-PD-1 failed melanoma being submitted.

"The findings shared for the IGNYTE clinical trial underscore the promising effects of RP1 shown to date, including overall response rate, durability and safety," said Michael Wong, M.D., Ph.D., Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and presenter of the study. "RP1 plus nivolumab provides an attractive risk-benefit profile for melanoma patients who have progressed on PD1 based treatment, particularly when compared with other therapies. For this population – the unmet need is significant as there are limited options with only about half of patients with melanoma responding to first line treatment."

Oral Presentation: Safety, Efficacy, and Biomarker Results from an Open-Label, Multicenter, Phase 1 Study of RP2 Alone or Combined with Nivolumab in a Cohort of Patients with Uveal Melanoma (Session: Melanoma/Skin Cancers, June 3, 2024, 9:57AM CDT; Location: S406; Abstract: 9511)

The data suggest that RP2, which expresses an anti-CTLA-4 antibody, dosed both alone and in combination with an anti-PD-1 agent in metastatic uveal melanoma patients (n=17), including those with both liver and extra-hepatic metastases, had a favorable safety profile and durable anti-tumor activity.
RP2 administered as monotherapy or in combination with nivolumab demonstrated an ORR of 29.4%, with a disease control rate (DCR) of 58.8%.
Biomarker data indicate immune cell infiltration and increased PD-L1 expression in tumors, together with changes in the systemic T cell repertoire following RP2 plus nivolumab.
Based on the encouraging ORR observed amongst a patient population with historically poor treatment outcomes, Replimune is currently finalizing the protocol for a registration-directed study based on FDA input.
Both presentations will be available on the Company website under Events and Presentations.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

About RP2
RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

On June 3, 2024 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported the issue of a new Chinese patent notice of allowance for opaganib4 in combination with immune checkpoint inhibitors (ICIs) as a method of inducing an anti-cancer immune response, providing protection for opaganib’s potential use with a range of approved and in-development immune checkpoint inhibitors (ICIs) across a growing range of indications through 2040 (Press release, RedHill Biopharma, JUN 3, 2024, View Source [SID1234644022]). The patent will be issued by the Chinese National Intellectual Property Administration (CNIPA) (Chinese Patent Application No.: 202080013805.3 issued May 24, 2024).

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"ICIs have become a cornerstone in cancer treatment, having been hailed as a major breakthrough by oncologists, with the global ICI market expected to exceed $100 billion by 2028, including Merck’s Keytruda (pembrolizumab) and BMS’ Yervoy (ipilimumab)," said Guy Goldberg, RedHill’s Chief Business Officer. "This exciting new patent is based on compelling data from a range of in vivo experiments showing significant improvements in outcomes in combination with selected ICIs. China has been a world leader in embracing ICI-based therapy5 and this is an important addition to the strong patent portfolio protecting opaganib."

About Opaganib (ABC294640)
Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including prostate cancer and cholangiocarcinoma (bile duct cancer), gastrointestinal acute radiation syndrome (GI-ARS), Sulfur Mustard exposure, COVID-19, Ebola and other viruses as part of pandemic preparedness.

Opaganib’s host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

Opaganib has been selected for evaluation by two U.S. government countermeasures programs for Acute Radiation Syndrome (ARS) and Sulfur Mustard exposure, both funded by the NIH: The Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the HHS National Institutes of Health, for the nuclear medical countermeasures (MCM) product development pipeline selected opaganib for development as a potential treatment for Acute Radiation Syndrome (ARS); and the Chemical Medical Countermeasures (Chem MCM) Program and Chemical Countermeasures Research Program (CCRP), managed respectively by the Administration for Strategic Preparedness and Response (ASPR) / Biomedical Advanced Research and Development Authority (BARDA) and NIH/NIAID selected opaganib for evaluation as a potential medical countermeasure (MCM) against Sulfur Mustard exposure.

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury, Gilead Sciences Inc.), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study.

Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv.

Opaganib has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.

Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications.