On December 19, 2024 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for NX-5948, a highly selective degrader of Bruton’s tyrosine kinase (BTK), for the treatment of adult patients with relapsed or refractory Waldenstrom’s macroglobulinemia (WM) after at least two lines of therapy, including a BTK inhibitor (Press release, Nurix Therapeutics, DEC 19, 2024, View Source [SID1234649216]).

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"Fast Track designation for NX-5948 is an important recognition of the unmet patient need in Waldenstrom’s macroglobulinemia, particularly in the growing number of patients whose cancer has progressed following BTK inhibitor therapy," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "This designation follows encouraging safety and efficacy data from our ongoing Phase 1 clinical trial, demonstrating early promise of clinical benefit with potential for durable outcomes. We continue to enroll Waldenstrom’s macroglobulinemia patients in the ongoing Phase 1b expansion cohort and anticipate sharing additional clinical data in 2025."

In addition to the Fast Track designation announced today for Waldenstrom’s macroglobulinemia, NX-5948 previously received Fast Track designation in January 2024 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor. In November 2024, the European Medicines Agency (EMA) granted NX-5948 PRIME designation for the treatment of adult patients with relapsed or refractory CLL/SLL after at least a BTK inhibitor and a BCL2 inhibitor.

About Waldenstrom’s Macroglobulinemia

WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. The incidence of Waldenstrom’s macroglobulinemia ranges from 0.361,2 to 0.573 per 100,000 people in the United States or approximately 1,200 to 1,900 annually. With a median disease duration approaching 10 years,4 approximately 12,000 to 19,000 patients are living with Waldenstrom’s macroglobulinemia in the United States. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor therapy. There are no therapies approved to treat WM patients after BTKi.

About Fast Track Designation

The FDA’s Fast Track designation is intended to facilitate and expedite the development and review of drug candidates to treat serious conditions and fulfill an unmet medical need. To qualify, available clinical and non-clinical data need to demonstrate a therapeutic candidate’s potential to address this unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.

About PRIME Designation

The PRIME initiative, launched by the EMA in 2016, offers early, proactive and enhanced support to developers of promising medicines to optimize development plans and accelerate evaluation so these medicines can reach patients faster. To be eligible for PRIME, medicines must target an unmet medical need and show potential benefit for patients based on early clinical data.

About NX-5948

NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines that are resistant to current BTK inhibitor therapies, an important consideration in heavily pretreated CLL/SLL patient populations. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

On December 19, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported the positive outcome of a Type C Chemistry, Manufacturing, and Controls (CMC) meeting with the U.S. Food and Drug Administration (FDA) regarding production of IMNN-001 for the treatment of women with newly diagnosed advanced ovarian cancer (Press release, IMUNON, DEC 19, 2024, View Source [SID1234649215]). The goal of the meeting was to seek alignment and agreement with the FDA on key CMC topics to support IMNN-001 production for the planned Phase 3 pivotal trial and a potential future new biologic license application (BLA) submission. IMUNON remains on track to initiate the 500-patient Phase 3 trial of IMNN-001 in the first quarter of 2025.

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"We are very pleased with our recent FDA interactions as we continue to work collaboratively with the Agency to align on the most expeditious path to advance IMNN-001 into Phase 3 and toward potential commercialization for the thousands of women with newly diagnosed advanced ovarian cancer in need of additional treatment options," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "The FDA’s agreement with our plan to meet key CMC requirements is highly encouraging, establishing our ability to produce our gene-mediated therapeutic for our Phase 3 pivotal trial as well as creating a highly cost-efficient framework for potential commercialization."

The meeting with the FDA included a review of IMUNON’s current good manufacturing practice (cGMP) clinical-scale and commercial manufacturing process for IMNN-001, conducted at the company’s manufacturing facility based in Huntsville, Alabama. The Agency agreed that the company’s potency assay which measures interferon-gamma (IFN-γ) is acceptable for the Phase 3 clinical study and for use in a commercial setting for release of drug product. The FDA also agreed with the company’s strategy to establish comparability of the core components of IMNN-001 produced by IMUNON with product previously produced through an external contract development and manufacturing organization (CDMO).

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On December 19, 2024 Halia Therapeutics reported the second stage of a phase 2 trial exploring the first-in-class allosteric NEK7/NLRP3 inflammasome inhibitor HT-6184 for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) is launching following positive topline data from the initial cohort of 18 patients (Press release, Halia Therapeutics, DEC 19, 2024, View Source [SID1234649214]).

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Among the 18 patients with LR-MDS, a hematological improvement-erythroid response to HT-6184 was seen after 16 weeks of monotherapy. This exceeded the preset requirement of at least 3 responders.

The study will now advance to its second stage expansion, which will enroll an additional 8 to 10 patients.

"The high frequency of erythroid response following treatment with HT-6184 validates the key importance of the NLRP3 inflammasome and myddosome pathways as pathogenetic drivers of ineffective hematopoiesis in MDS, offering the prospect of a safe and effective oral therapeutic for LR-MDS patients," said Alan List, MD, Halia Therapeutics SAB Member, in a press release.

HT-6184 is a new drug candidate that works by targeting the protein NEK7 through an allosteric mechanism. Preclinically, it has been shown that inhibiting NEK7’s binding ability to NLRP3 disrupts inflammasome signaling and reduces the inflammatory response. In unpublished data from Halia Therapeutics, HT-6184 has also been shown to prevent the formation of the NLRP3 inflammasome and promotes its disassembly once activated.

In this phase 2 trial, investigators are using a Simon’s minimax two-stage design to evaluate HT-6184’s safety and efficacy in up to 40 patients. The study is ongoing across multiple clinical sites in India.

Hematologic improvements, including transfusion dependency and changes in hemoglobin levels, are the study’s primary end points. Secondary end points of the trial include evaluating HT-6184’s impact on biomarkers of inflammasome activation in MDS and the size of somatic gene mutation clones.

The study’s estimated completion date is by the end of Q2 of 2025. If positive, the results can support the agent’s continued clinical development and potential regulatory submission.

A phase 1 study of HT-6184 (NCT05447546) previously evaluated the agent’s safety and tolerability when given to patients as single or multiple oral doses at escalating levels. Now, a phase 2 trial is ongoing to study the efficacy of HT-6184 in the treatment of patients with LR-MDS, and another phase 2 study is assessing its impact on post-procedure diagnostic biomarkers of inflammation and pain (NCT06241742).

"This trial represents a significant step forward in addressing the unmet needs of patients with LR-MDS," said David J. Bearss, PhD, president and chief executive officer of Halia Therapeutics, in a press release. "By targeting the underlying inflammatory signaling driving this condition, HT-6184 aims to transform treatment outcomes and improve quality of life for patients who currently face limited options."

On December 19, 2024 FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, reported that William Hinshaw, Chief Executive Officer of Fore Biotherapeutics, will present at the 43rd Annual J.P. Morgan Healthcare Conference (Press release, Fore Biotherapeutics, DEC 19, 2024, View Source [SID1234649213]). The presentation will take place on Tuesday, January 14, 2025, at 5:30 p.m. PT at the Westin St. Francis Hotel in San Francisco.

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Mr. Hinshaw will detail progress and anticipated milestones for Fore’s lead asset, plixorafenib, a novel, small-molecule, next generation, orally available selective inhibitor of mutated BRAF. Plixorafenib is currently being evaluated in a clinical trial with registrational intent in three distinct indications.

Please contact Argot Partners to schedule one-on-one meetings with the management team.

On December 19, 2024 Epitopea, a transatlantic cancer immunotherapeutics company developing accessible off-the-shelf RNA-based immunotherapies, and Genevant Sciences, a leading nucleic acid delivery company with world-class platforms and a robust and expansive lipid nanoparticle (LNP) patent portfolio, reported that they have entered into a collaboration and nonexclusive license agreement to develop novel mRNA-LNP immunotherapies targeting Epitopea’s proprietary aberrantly-expressed tumor specific antigens (aeTSAs), called CryptigensTM, for an undisclosed oncology indication (Press release, Epitopea, DEC 19, 2024, View Source [SID1234649212]).

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"At Epitopea we continue to accelerate our near-term clinical development plans for our next generation, tumor selective, off-the-shelf, RNA-based immunotherapies that we believe have the potential to extend the durability of clinical responses in patients. Access to world-class LNP delivery technology in support of our vision is critical. Genevant is a longstanding leader in the LNP space, and we are excited about the translational path forward,"

said Alan Rigby, Chief Executive Officer of Epitopea.

"Our clinically validated LNP technology and decades of experience in the space make us a partner of choice for innovative RNA-based immunotherapy companies," said James Heyes, Chief Scientific Officer of Genevant Sciences. "We are delighted to be collaborating with the Epitopea team and supporting its mission to extend the durability of clinical response in cancer patients."

Under the terms of the agreement, Genevant granted to Epitopea a nonexclusive worldwide license to certain Genevant LNP technology to develop RNA-based immunotherapies targeting Epitopea’s Cryptigen TSAs in an undisclosed oncology indication. Genevant is eligible to receive up to $123.5 million in upfront and contingent milestone payments per product and tiered royalties ranging from the mid to high single digits on future product sales.