On February 16, 2024 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported that new post-hoc subgroup analyses and pharmacodynamic data will be presented on APHEXDA (motixafortide) for CD34+ hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood and Marrow Transplant Research (CIBMTR), taking place February 21-24, 2024, in San Antonio, Texas (Press release, BioLineRx, FEB 16, 2024, View Source [SID1234640184]).

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Results include pharmacokinetics (PK) and pharmacodynamics (PD) data as well as post-hoc subgroup analyses from the Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim, compared to placebo plus filgrastim (G-CSF), for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Phase 1 study results demonstrated an extended PD effect with complete receptor occupancy by motixafortide starting at a concentration of 3nM. In the GENESIS trial, post-hoc subgroup analyses based on baseline characteristics and risk factors for impaired HSC mobilization demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients.

Poster Presentations at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the ASTCT and the CIBMTR.

Henry B. González Convention Center, San Antonio, Texas

Poster Session Details

Poster: Number 537. See abstract.
Title: Motixafortide Enables Consistent, Robust Hematopoietic Stem Cell Collection (HSC) across Populations with Increased Impaired HSC Mobilization: A Sub-Group Analysis of the Genesis Study

Presenter: Zachary D. Crees, MD, Washington University School of Medicine in St. Louis

Poster Session: Myeloma – Clinical

Date: Thursday, February 22, 2024

Time: 6:45 PM – 7:45 PM

Poster: Number 535. See abstract.
Title: Prolonged CXCR4 Receptor Occupancy By Motixafortide Following a Single Subcutaneous Injection Is Associated with Extended Mobilization of CD34+ Cells in Peripheral Blood for > 24 Hours

Presenter: Ella Sorani, PhD, BioLineRx Ltd

Poster Session: Myeloma – Clinical

Date: Thursday, February 22, 2024

Time: 6:45 PM – 7:45 PM

About the GENESIS Trial
GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study. The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.

About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.1 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

About APHEXDA APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.2

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide.

WARNINGS AND PRECAUTIONS

Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs.
Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed.
Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose.
ADVERSE REACTIONS
The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%).

USE IN SPECIFIC POPULATIONS

Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity.

Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose.

Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients.

Please see the accompanying full Prescribing Information.

On February 15, 2024 Gilead Sciences, Inc. reported that it has paused enrollment globally in the magrolimab solid tumor studies. The U.S. Food and Drug Administration (FDA) subsequently requested a partial clinical hold on these trials (Press release, Gilead Sciences, FEB 15, 2024, View Source [SID1234640174]). This request is in addition to the previously announced full clinical hold on all magrolimab studies in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) requested by the FDA. Gilead is reviewing the benefit-risk of magrolimab across all ongoing trials and will provide an update on this assessment as soon as possible.

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Patients already enrolled in the Gilead-sponsored ELEVATE solid tumor studies and deriving clinical benefit may continue to choose receiving magrolimab following reconsenting to the study with their healthcare provider.

The Gilead-sponsored ELEVATE solid tumor studies impacted by the partial clinical hold include:

Phase 2 study in head and neck squamous cell carcinoma (NCT04854499)
Phase 2 study in solid tumors (NCT04827576)
Phase 2 study in triple-negative breast cancer (NCT04958785)
Phase 2 study in colorectal cancer (NCT05330429)
The enrollment hold also applies to Investigator Sponsored Studies with magrolimab in solid tumors.

On February 15, 2024 Firefly Bio reported that the company emerged from stealth mode with a $94 million Series A financing co-led by founding investor Versant Ventures and by MPM BioImpact alongside Decheng Capital and with participation from Eli Lilly & Company (Press release, Firefly Bio, FEB 15, 2024, View Source [SID1234640173]). Firefly has developed a novel platform to treat cancer using degrader antibody conjugates (DACs).

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DACs represent the convergence of two technologies – antibody drug conjugates (ADCs) and protein degraders. Despite the power of each approach, both have important limitations. While traditional ADCs have favorable bioavailability and the ability to target cells, they often have a limited therapeutic index due to their broadly cytotoxic payloads. Additionally, ADCs lack the ability to knock down specific intracellular proteins.

With protein degraders, the converse is true – these therapies have intracellular selectivity, protein knock down, and are highly catalytic. However, they struggle with bioavailability and do not have the ability for cell-specific targeting.

Firefly’s platform combines the respective strengths of ADCs and degraders while overcoming their deficiencies. The result is a new class of therapeutics able to precisely drug a range of intracellular biological targets that were previously hampered by therapeutic index issues when delivered systemically.

"DACs are a new modality for cancer," said Firefly CEO Scott Hirsch. "They give us the ability to hit biologically validated targets with minimal collateral damage. Our platform enables DACs at scale and vastly expands the number of payloads for ADCs."

An Industry-Leading Platform
Firefly’s platform uses potent catalytic protein degraders as the payloads of ADCs. The company’s proprietary Firelink linker technology joins these modalities, decreasing free payload in circulation and minimizing uptake in healthy cells. This leads to lower doses needed for optimal efficacy. In preclinical studies in both solid and liquid tumors, single administration of Firefly’s DACs showed significant reductions in tumor volume at very low doses.

Firefly was incubated in close collaboration with scientists at Versant’s Ridgeline Discovery Engine in the Basel Technology Park. These efforts helped the company rapidly establish proof-of-concept and advance its lead asset.

"At Firefly, we’ve assembled a unique talent base and platform to significantly advance this promising field," said Jerel Davis, Ph.D., Managing Director at Versant and a Firefly board member. "The company has made rapid progress and is poised to become the leader in discovering clinically meaningful DACs in oncology and immunology."

"Firefly is the first company with a platform specifically suited for DACs," said Todd Foley, managing director at MPM BioImpact and a Firefly board member. "The company’s platform upgrades multiple aspects of existing linker technologies and does so all under one roof, making it ideally positioned to pioneer these new therapies."

Leadership Team and Founders

Firefly is led by experienced executives with a deep history and expertise in biotech creation, ADC development, and degrader chemistry. The team is led by CEO, Scott Hirsch who was previously Chief Operating Officer at Allakos and has overseen multiple early- and late-stage ADC programs as well as directly managed commercial, portfolio, and operations teams. Co-founder and CSO John Flygare, Ph.D., previously led ADC teams at Genentech and Merck and has advanced ADCs and degraders into the clinic. Co-founder and CTO Bernhard Geierstanger, Ph.D., is a biotherapeutics expert and previously led ADC teams at Novartis and Merck and built protein modification and conjugation platforms. Co-founder Carolyn Bertozzi, Ph.D., was awarded the 2022 Nobel Prize in Chemistry for her work in bioorthogonal chemistry and is a world expert in ADCs.

On February 15, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the first patient has been dosed in the Company’s Phase 1 LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial evaluating RP-1664, a potential first-in-class, highly selective, oral polo-like kinase 4 (PLK4) inhibitor, for the monotherapy treatment of adult and adolescent patients enriched for TRIM37-high solid tumors (Press release, Repare Therapeutics, FEB 15, 2024, View Source [SID1234640172]).

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"RP-1664 exhibited deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor and neuroblastoma xenograft models, both internally and in collaboration with Children’s Hospital of Philadelphia. After evaluating safety in the LIONS clinical trial, we expect to move rapidly into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which patients have a high prevalence of TRIM37-altered tumors and limited treatment options," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "RP-1664 is Repare’s third internally-developed clinical therapeutic candidate, a testament to the productivity of our platform."

The LIONS clinical trial (NCT06232408) is a first-in-human, multicenter, open-label Phase 1 study to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664. The clinical trial is expected to enroll approximately 80 patients with molecularly selected advanced solid tumors, including those with gain or amplification of TRIM37, among other genetic alterations. The primary endpoints are to determine the safety, tolerability, dose and schedule of RP-1664 and assess any early antitumor activity.

About RP-1664

RP-1664 is a potential first-in-class, highly selective, oral PLK4 inhibitor designed to harness the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for centriole biogenesis in S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is high. Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in approximately 80% of all high-grade neuroblastomas. RP-1664 is the only selective PLK4 inhibitor known to be in the clinic.

On February 15, 2024 CEL-SCI Corporation (NYSE American: CVM) reported financial results for the quarter ended December 31, 2023, as well as key recent clinical and corporate developments (Press release, Cel-Sci, FEB 15, 2024, View Source [SID1234640171]).

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Clinical and Corporate Developments include:

CEL-SCI identified the target head and neck cancer patient population for Multikine (Leukocyte Interleukin, Injection)* that will be the basis for the Company’s regulatory filings for marketing clearance. In October 2023, the new data were presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The target population, which saw its 5-year risk of death cut in half, can be identified prior to surgery upon diagnosis with tests that physicians routinely use in cancer screenings, a key finding for Multikine, which is a neoadjuvant therapy. A summary of Multikine’s results in the target population include the following:
73% survival for Multikine vs 45% in the control at 5 years
28% absolute survival benefit
Statistically significant p = 0.0015 and hazard ratio = 0.35
Tumor reduction rate >13% and tumor downstaging >35%
No safety signals or toxicities vs standard of care
Target population of an estimated 145,000 patients (global, annual) with newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) who present with:
No lymph node involvement (via PET scan)
Low PD-L1 tumor expression (TPS<10) (via biopsy).
Physicians routinely assess these features at baseline; no extra tests needed. These features make it easy to write a label for Multikine, which is essential for drug approval
CEL-SCI estimates that low PD-L1 patients represent about 70% of locally advanced primary SCCHN patients
CEL-SCI issued a comprehensive Letter to Shareholders detailing the data reported on the efficacy of Multikine in the head and neck cancer target patient population
CEL-SCI’s cGMP state-of-the-art dedicated manufacturing facility commissioning was completed, a significant milestone toward a planned Biologics License Application (BLA) with several regulatory agencies for approval of Multikine. The Company’s manufacturing trade secrets, capabilities, and know-how are high-value key strategic assets that are very difficult for others to replicate.
The United Kingdom’s (UK) National Institute for Health and Care Excellence (NICE) selected Multikine to be evaluated as the potential new standard of care for SCCHN. NICE posted a detailed report from the UK’s National Institute for Health and Care Research (NIHR) regarding Multikine, its clinical data, and its potential to become a better standard of care in treating newly diagnosed head and neck cancer in the UK.
The European Medicines Agency’s (EMA) Paediatric Committee granted CEL-SCI a product-specific waiver of strict requirements for commercialization of cancer drugs in the European Union (EU). The waiver is a big step forward for Multikine, as it removes a major hurdle on the path towards commercialization in Europe.
CEL-SCI plans to submit the target population data to the U.S. Food and Drug Administration (FDA) this quarter. Health Canada advised CEL-SCI to request advance consideration for approval under a Notice of Compliance with Conditions (NOCC) policy. Meetings with the UK regulators and the EMA are expected H1 2024.
"Following the identification of our focused patient population, backed by robust efficacy data, we have made progress with global regulators, including in the UK and EU where we expect meetings in the coming months. Our manufacturing facility is fully commissioned and should soon be ready for commercial-scale production," stated CEL-SCI CEO, Geert Kersten. "We are optimistic about working with regulators to get Multikine to the patients who need it. Statistically significant data demonstrate our target patient population can benefit from a longer life with Multikine."

Financial Results

The Company incurred a net operating loss of approximately $6.5 million for the three months ended December 31, 2023, approximately $2.6 million of which was non-cash expenses.

During the three months ended December 31, 2023, research and development expenses decreased by approximately $1.0 million, or 19%, compared to the three months ended December 31, 2022. During the three months ended December 31, 2023, general and administrative expenses decreased by approximately $0.1 million, or 6%, compared to the three months ended December 31, 2022.

CEL-SCI raised $5 million in November 2023 and $7.75 million in February 2024, both through public offerings of common stock.