On December 16, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has completed the Phase 1 dose escalation portion of the Acclaim-3 clinical trial of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy to treat patients with extensive stage small cell lung cancer (ES-SCLC) (Press release, Genprex, DEC 16, 2024, View Source [SID1234649130]). In addition, the Safety Review Committee (SRC) has approved the opening of the Phase 2 expansion portion of the trial.

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The combination of REQORSA and atezolizumab previously received U.S. Food and Drug Administration’s (FDA) Fast Track Designation for the treatment of the Acclaim-3 patient population, and the FDA has also granted Orphan Drug Designation to REQORSA for the treatment of SCLC.

Based on full safety data, which showed no dose limiting toxicities (DLTs), the SRC determined that the Recommended Phase 2 Dose (RP2D) of REQORSA will be 0.12 mg/kg. This was the highest dose level delivered in the Phase 1 portion of the trial. The SRC also recommended the trial advance to the Phase 2 expansion portion of the study, which the Company has now opened for enrollment.

"We are pleased to complete the Phase 1 dose escalation portion of the Acclaim-3 clinical trial and to have now opened the Phase 2 expansion portion of Acclaim-3 for enrollment in the second half of 2024, in accordance with our previously disclosed guidance for timing and milestones," said Ryan Confer, President and Chief Executive Officer at Genprex. "Our partnership with a large network of community-based oncology practices has allowed us to have successful enrollment rates, enabling Genprex to meet our 2024 timeline targets for this study. In adding multiple clinical trial sites to our Acclaim-3 study, we have been able to more efficiently and expeditiously accelerate the Acclaim-3 clinical trial. Looking ahead, we believe this sets the stage for potential promising enrollment rates for the Phase 2 portion of the trial. Additionally, we will be submitting the results of the Phase 1 portion of the study to a clinical meeting and anticipate data presentation in 2025, and we remain encouraged by the early efficacy demonstrated in ES-SCLC patients."

Genprex previously reported the first patient treated in the Phase 1 dose escalation portion of the Acclaim-3 trial had a partial remission, which is defined as at least a thirty percent (30%) decrease in tumor size, from prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. A CT scan performed after four cycles of maintenance therapy (three months), confirmed that the patient had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at that time. As the maintenance therapy consists of REQORSA and Tecentriq, and the patient had already received four cycles of Tecentriq during induction therapy and thus responses to Tecentriq would likely have occurred earlier, the Company believes this suggests that REQORSA may be providing clinical benefit.

In the Phase 1 dose escalation portion of the Acclaim-3 clinical trial, patients were treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity was experienced. The primary endpoint of the Phase 1 escalation portion was to determine the Maximum Tolerated Dose (MTD) or RP2D.

The SRC is comprised of three physicians who are principal investigators in the trial. Based on the preliminary safety data from patients in the 0.12 mg/kg dose level, the SRC recommended that the 0.12 mg/kg dose be the RP2D that will be used in the Phase 2 portion of the trial and that the Phase 2 trial be opened for enrollment.

The Phase 1 dose escalation portion of the trial had two dose groups: 0.09 mg/kg and 0.12 mg/kg.The Phase 2 expansion portion will enroll approximately 50 patients at approximately 10 to 15 U.S sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 2 portion is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. A Phase 2 futility analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.

Data presented at the October 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) from studies in humanized mouse models of SCLC that use human H841 cells have shown that the combination of REQORSA and Tecentriq provides significantly better control of tumor burden than either agent alone. The data from these studies also suggest that a combination treatment of REQORSA and Tecentriq can promote a significantly increased tumor cell killing effect in SCLC xenografts compared to that of Tecentriq alone.

About Acclaim-3

The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, Reqorsa Gene Therapy, in combination with Genentech, Inc.’s Tecentriq (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment.

On December 16, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported that David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene, will present at the 43rd Annual J.P. Morgan Healthcare Conference at the Westin St. Francis in San Francisco (Press release, Allogene, DEC 16, 2024, View Source [SID1234649124]).

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43rd Annual J.P. Morgan Healthcare Conference
Wednesday, January 15, 2025
3:00PM PT/ 6:00PM ET

A live audio webcast of the presentation will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section.

Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On December 16, 2024 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines to treat serious diseases by correcting abnormal gene expression, reported that it has made the decision to discontinue the independent development of FHD-286 in combination with decitabine in patients with relapsed and/or refractory acute myeloid leukemia (AML) (Press release, Foghorn Therapeutics, DEC 16, 2024, View Source [SID1234649122]). Foghorn is evaluating partnerships and ISTs (Investigator Sponsored Trials) to advance FHD-286. The Company will prioritize its proprietary pipeline and Lilly collaboration programs, including the clinical-stage selective SMARCA2 (BRM) inhibitor FHD-909 (LY4050784).

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As of September 30, 2024, the Company had $267.4 million in cash, cash equivalents and marketable securities. Its cash runway supports the Company into 2027.

In the Phase 1 dose escalation trial of FHD-286 in combination with decitabine in relapsed and/or refractory AML, objective clinical responses were observed by standard response criteria. However, the observed response rate did not meet the Company’s threshold to continue development by Foghorn alone. Foghorn expects to report the results at a medical conference in 2025.

"While clinical responses were observed for FHD-286, we will prioritize investment into our proprietary pipeline, including our Selective CBP program, Selective EP300 program, and ARID1B program, as well as our Lilly collaboration, including the clinical development of FHD-909." said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "Our pipeline of potential medicines represents significant opportunities in oncology with the potential for therapeutic expansion. We want to thank the clinical investigators, the patients, and their families for their participation in the FHD-286 clinical trial."

About FHD-286
FHD-286 is a highly potent, first-in-class, selective, allosteric, and orally available small-molecule, enzymatic inhibitor of SMARCA2 (BRM) and SMARCA4 (BRG1), two highly similar proteins that are the ATPases, or the catalytic engines, of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies, including both hematologic and solid tumors.

About AML
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

On December 16, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported new findings published in Science Immunology that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans (Press release, Immutep, DEC 16, 2024, View Source [SID1234649116]). The publication is the first to show the crystal structure of a human LAG3/HLA-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.

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Under the oversight of Professor Jamie Rossjohn FAA FRS, at Monash University’s Biomedicine Discovery Institute (BDI), and in collaboration with Immutep, this breakthrough is an exemplar of the importance of industry-academia alliances. The LAG-3 immune control mechanism is the exclusive focus of Immutep across both cancer and autoimmunity and a clinically validated target of deep interest throughout the academic, medical, and industry sectors.

Dr. Jan Petersen, first author of the study,said: "The way the PD-1 and CTLA-4 immune checkpoint molecules bind to their respective ligands has been resolved for many years. However, the resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, has remained elusive. Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural foundation to harness rationally for future development of antibodies and small molecule therapeutics designed to block LAG-3 activity."

Dr. Frédéric Triebel, Immutep’s CSO, added: "It is thrilling to be able to see and analyze the interactions taking place at the interface between the soluble homodimeric LAG-3 protein and its main ligand. We now better understand how efti uniquely acts as an MHC-II agonist by preferentially binding to a subset of MHC-II molecules clustered in lipid raft microdomains on the surface of antigen-presenting cells. These findings add to the strong foundation of our work with Professor Rossjohn and his team to develop a deeper understanding of the structure and function of the LAG-3 immune control mechanism, particularly as it relates to our antiLAG-3 small molecule program."

The Crystal Structure of the Human LAG-3–HLA-DR1–Peptide Complex publication details how LAG-3 engages two HLA-II molecules (see Figure 1). The data in the publication supports efti’s (soluble LAG-3) preferential binding to a subset of MHC-II molecules on antigen-presenting cells leading to their activation

On December 15, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, and Eli Lilly and Company (NYSE: LLY) today jointly announced a Distribution and Promotion Agreement in Mainland China regarding Lilly’s non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, Jaypirca (pirtobrutinib, 100 mg & 50 mg tablets). The agreement highlights the following aspects:

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Innovent will be responsible for the importation, marketing, distribution and promotion of Jaypirca;
Lilly will be responsible for the R&D and post-market medical affairs of Jaypirca.
Jaypirca, a highly selective kinase inhibitor, utilizes a novel non-covalent binding mechanism to re-establish BTK inhibition in mantle cell lymphoma (MCL) patients previously treated with a covalent BTK inhibitor (approved including ibrutinib, acalabrutinib, zanubrutinib, or orelabrutinib) and extend the benefit of targeting the BTK pathway, thus effectively addressing the unmet clinical needs for these patients. Approved by the U.S. FDA in January 2023, Jaypirca (pirtobrutinib) became the first and only approved non-covalent (reversible) BTK inhibitor. In October 2024, Jaypirca (pirtobrutinib) received approval from China’s National Medical Products Administration (NMPA) as monotherapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two types of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor (Link).

Lilly is conducting comprehensive global Phase 3 development programs (including in China), in first-line and relapse or refractory patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and BTK inhibitor-naïve relapse or refractory MCL, to explore monotherapy or combination therapy.

Under the agreement, Innovent holds the sole commercialization rights for Jaypirca in Mainland China, overseeing importation, marketing, distribution and promotion. Lilly will be responsible for R&D and post-market medical affairs. Leveraging Innovent’s established hematology oncology commercial team and Lilly’s deep expertise in drug development and scientific insights in the therapeutic area, the partnership is committed to broadening access to innovative treatments and improving outcomes for cancer patients in Mainland China.

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "Building on our long-term strategic collaboration with Lilly, we are proud to expand our collaboration through this agreement. Jaypirca, the world’s first and only approved non-covalent (reversible) BTK inhibitor, represents a breakthrough treatment option for patients who have previously received BTK inhibitors. Innovent has built a robust and leading portfolio in the hematological malignancy field, consisting of TYVYT (sintilimab injection), HALPRYZA (rituximab injection), olverembatinib, FUCASO (Equecabtagene Autoleucel Injection), and Jaypirca. By fully leveraging our commercialization capabilities and extensive coverage in this field, we aim to bring forward innovative medicines to benefit cancer patients and further enhance our leading position in oncology. We remain steadfast in our commitment to advancing the biopharmaceutical industry through collaborative efforts so that first-rate pharmaceutical drugs can become widely accessible."

Huzur Devletsah, President and General Manager of Lilly China, states, "Lilly is thrilled to appoint Innovent for the distribution and promotion of Jaypirca marking a pivotal moment in hematologic cancer treatment for Lilly. This agreement allows to rapidly increase patient access in Mainland China by drawing on Innovent’s robust market presence and our extensive R&D expertise. Together, we are poised to deliver innovative therapies and support the ‘Healthy China 2030’ initiative, continuing our commitment: ‘In China, For China."

About Jaypirca (pirtobrutinib)

Jaypirca (pirtobrutinib, formerly known as LOXO-305) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.[i] BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma.[ii],[iii]

About Innovent’s strategic cooperation with Lilly

Innovent and Lilly have established a comprehensive level of cooperation, setting an example of partnership between a Chinese innovative pharmaceutical company and a global leading medicine company in the field of R&D, CMC, clinical development and commercialization, aiming to accelerate the access of innovative medicines to benefit more patients worldwide.

In March 2015, Innovent entered into a strategic partnership with Lilly focused on biological medicine. Under the initial agreement, Lilly and Innovent co-developed and co-commercialized oncology medicines, including Tyvyt (sintilimab injection) in China. In October 2015, the two parties announced the extension of collaboration to include the co-development of three additional antibodies in oncology. In August 2019, the cooperation extended with a licensing agreement for the development and commercialization of a potentially global best-in-class investigational GCG/GLP-1 medicine in China. In August 2020, Innovent and Lilly announced a global expansion of their strategic alliance for sintilimab. In March 2022, Lilly and Innovent deepened their engagement in oncology, granting Innovent sole commercialization rights for Cyramza (ramucirumab) and Retsevmo (selpercatinib), and a right of first negotiation for potential future commercialization of Jaypirca (pirtobrutinib) in Mainland China. In December 2024, the agreement of the commercialization of Jaypirca (pirtobrutinib) in Mainland China officially achieved.