On October 24, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported preclinical data supporting the development of the Company’s menin inhibitor, ziftomenib, for the treatment of advanced gastrointestinal stromal tumors (GIST) (Press release, Kura Oncology, OCT 24, 2024, View Source [SID1234647368]).

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The new findings are being presented at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona. A copy of the poster, entitled "Menin Inhibitor Ziftomenib Synergizes with Imatinib in Tyrosine Kinase Inhibitor (TKI)-Resistant Gastrointestinal Stromal Tumor Models," is available in the Posters and Presentations section on Kura’s website.

"Kura has generated a substantial body of preclinical data that support potential for ziftomenib in combination with KIT inhibitors for the treatment of patients with advanced GIST," said Francis Burrows, Ph.D., Senior Vice President, Translational Research. "Our results indicate that the combination of ziftomenib and imatinib acts via a synthetic lethal mechanism through which ziftomenib targets an epigenetic vulnerability of GIST tumors, creating potent synergy even with KIT inhibitors that are otherwise inactive as monotherapy. Indeed, the activity of ziftomenib appears to be agnostic to the mutational status of KIT in GIST, suggesting an opportunity to explore the combination for all patients, even in the frontline setting."

The combination of ziftomenib and imatinib unexpectedly showed robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. Mechanistically, the data reveal a KIT-dependent mechanism, with ziftomenib and imatinib combining to sharply reduce KIT expression and/or activity, effectively silencing both the ERK and AKT/mTOR signaling pathways and driving robust cell cycle arrest and apoptosis.

Given that imatinib is well established as the frontline standard of care in patients with GIST, and that generic versions are available, imatinib represents a promising combination partner for ziftomenib.

In August 2024, Kura announced clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for ziftomenib for the treatment of advanced GIST. The Company is now preparing to initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST after imatinib failure in the first half of 2025. For more information regarding the study, please visit www.clinicaltrials.gov (identifier: NCT06026410).

About GIST

Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, characterized as KIT-dependent solid tumors. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib can target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed. Previously published data show that the menin-MLL complex regulates KIT expression in GIST cells, and menin inhibitors display additive therapeutic activity in combination with imatinib in imatinib-sensitive GIST models1.

About Ziftomenib

Ziftomenib is a potent, selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

On October 24, 2024 Immunotherapy innovator ImmunityBio, Inc. (NASDAQ: IBRX), reported that the first patients have been dosed in an initial trial studying the potential of the company’s CAR-NK cell therapy targeting CD-19 in the treatment of non-Hodgkin’s lymphoma (NHL) (Press release, ImmunityBio, OCT 24, 2024, View Source [SID1234647367]). In the QUILT 106 trial, CD19-targeted high-affinity natural killer (t-haNK) cells are being tested initially as a single agent, and after demonstrating safety, then in combination with standard NHL treatment rituximab, in participants with selected CD19+ and CD20+ relapsed/refractory B-cell NHL. The phase 1, open label clinical study is designed to enroll up to 10 participants and is being conducted in Johannesburg, Pretoria, and Bloemfontein, South Africa.

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This is the first cellular-targeted natural killer (NK) cell therapy study ever to be conducted in South Africa, and is designed to provide important clinical information on a cancer with a significant rate of diagnosis in the region, but with few treatment options. Non-Hodgkin’s lymphoma is the 6th most common malignancy among people in Sub-Saharan Africa and it is the 4th most diagnosed cancer in men and the 5th most diagnosed cancer in women in South Africa, according to the Cancer Association of South Africa.

"This trial is important for ImmunityBio as our first clinical study of our CAR-NK, CD19 t-haNK cell line, as well as one of our first studies in liquid tumors," said Patrick Soon-Shiong, M.D., Executive Chairman, Founder and Global Chief Scientific and Medical Officer at ImmunityBio. "We have chosen to undertake this trial because Sub-Saharan African and, in particular, South African populations are often overlooked when it comes to advanced clinical research, despite the need for innovative immunotherapies in the region."

Full patient enrollment in this Phase 1 study of CD19 t-haNK is currently expected in the first quarter of calendar year 2025 with topline data readout expected in the second half of the calendar year 2025.

This study, being conducted in South Africa, is similar to ImmunityBio’s U.S.-based trial QUILT 3.092, a phase 1 open-label study of CD19 t-haNK as a single agent and in combination with the company’s IL-15 superagonist (N-803; ANKTIVA) and rituximab in participants with relapsed or refractory NHL.

About the QUILT 106 Study

The Phase 1, first-in-human (FIH), open-label study is designed to enroll up to 10 participants at sites in Johannesburg, Pretoria, and Bloemfontein, South Africa with the primary endpoint of the trial to evaluate the safety and preliminary efficacy of CAR-NK, CD19 t-haNK as a single agent and in combination with rituximab in participants with selected CD19+ and CD20+ R/R B-cell non-Hodgkin lymphoma (NHL). Participants will initially receive a single 3-week cycle of the CD19 t-haNK as a single-agent regime. Following a 1-week safety pause, participants will then receive a 3-week cycle of CD19 t-haNK in combination with rituximab. Patients will undergo multiple assessments of safety and efficacy to help evaluate the safety of CD19 t-haNK as a single agent and in combination with rituximab in participants with R/R NHL, who have active disease after completing ≥ 2 lines of cytotoxic chemotherapy.

About CAR-NK, CD19 t-haNK

CD19 t-haNK is a human, allogeneic, stable clonal NK cell line generated from the parental activated NK (aNK) cell line (NK-92). Based on the demonstrated therapeutic efficacy of chimeric antigen receptor (CAR) targeting and on the important role of FcγR-mediated antibody-dependent cellular cytotoxicity (ADCC) in the effectiveness of therapeutic IgG1 monoclonal antibodies, it was hypothesized that modification of the parental aNK cell line to stably express both a CD19-targeted CAR and the high-affinity variant of CD16 would result in potent and selective antitumor activity. Therefore, the novel CD19 t-haNK cells have been genetically engineered to stably express 3 main proteins: (1) a human CD19-targeted CAR; (2) the high-affinity variant of the human Fcγ receptor (FcγRIIIa/CD16a 158V) for enhanced ADCC; and (3) endoplasmic reticulum-retained version of human interleukin-2 (ERIL-2) for independent growth.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a heterogeneous disease that most commonly originates in B lymphocytes. In 2020, according to the South Africa National Cancer Registry (SANCR 2020), it is estimated that 1 in 174 men and 1 in 288 women will develop NHL. According to Global Cancer Observatory (Sung 2021), the incidence of NHL is 4.1% of all cancers. A comparative study of the distribution of NHL subtypes in South Africa reported that Southern Africa had a significantly lower proportion of low-grade B cell NHL (34.3%) and a higher proportion of high-grade B cell NHL (51.5%) compared to Western Europe (54.5% and 36.4%) and North America (56.1% and 34.3%) (Perry 2015).

On October 24, 2024, Genprex, Inc. ("Genprex" or the "Company") reported that the Company has entered into a Sponsored Research Agreement ("SRA") with the University of Michigan Rogel Cancer Center to study TUSC2, the tumor suppressor gene used in Genprex’s lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), in combination with ALK-inhibitors in ALK-EML4 positive translocated lung cancer (Press release, Genprex, OCT 24, 2024, View Source [SID1234647366]). The Company also announced its collaboration with ALK Positive, a non-profit patient-driven research organization dedicated to improving the life expectancy and quality of life for ALK-positive (ALK+) lung cancer patients. As a part of this collaboration, both Genprex and ALK Positive will share the cost of the SRA with the University of Michigan Rogel Cancer Center.

The Company noted in its press release that as the Company further expands its research program to new tumor targets, REQORSA in combination with ALK-inhibitors could be a potential therapeutic treatment for ALK+ lung cancer. TUSC2 is a tumor suppressor gene that is frequently deleted in lung cancer. Research collaborators at the Rogel Cancer Center’s Judith Tam ALK Lung Cancer Research Initiative presented positive preclinical data at the April 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, reporting that REQORSA induced apoptosis in alectinib resistant EML4-ALK positive non-small cell lung cancer ("NSCLC") cell lines. Alectinib is an ALK-inhibitor commonly used to treat patients with ALK rearrangements such as EML4-ALK positive NSCLCs. Researchers found that overexpressing TUSC2 using REQORSA treatment in ALK+ lung cancer cell lines inhibited the ability of the cells to form colonies. Ultimately, the study found that the use of REQORSA or a TUSC2-containing plasmid to overexpress TUSC2 in ALK+ NSCLC cell lines was effective in decreasing cell growth and proliferation through the activation of apoptotic pathways. Researchers believe the results of this preclinical work support further clinical study of REQORSA as an anti-ALK NSCLC treatment strategy, and Genprex believes this research suggests that REQORSA may be an effective treatment in patients progressing on alectinib.

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On October 24, 2024, Erasca, Inc. (the Company) reported preliminary data from its SEACRAFT-1 Phase 1b trial in an oral presentation at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium (Press release, Erasca, OCT 24, 2024, View Source [SID1234647365]).

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In the Phase 1b trial of naporafenib plus trametinib (MEKINIST) in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations, the preliminary clinical activity of naporafenib plus trametinib in the melanoma cohort include, as of the efficacy cutoff date*:

•
40% (4/10) response rate observed in the efficacy-evaluable patients with NRAS Q61X melanoma, including three confirmed partial responses and one unconfirmed partial response; the melanoma cohort in SEACRAFT-1 is generally representative of the patient population currently being enrolled in the pivotal SEACRAFT-2 trial
•
70% (7/10) of patients remained on treatment as of the data cutoff, including all four responders

*Safety data cutoff date was September 3, 2024. Efficacy data cutoff date was September 5, 2024.

Naporafenib plus trametinib has been generally well tolerated as of the safety cutoff date, with mostly low-grade adverse events in the majority of patients. The Company believes that the use of mandatory primary rash prophylaxis helped reduce the frequency and severity of skin toxicities, reduced drug discontinuation rate due to adverse events, and improved the observed tolerability as measured by the increased relative dose intensity, as compared to the prior clinical trials of naporafenib plus trametinib conducted by Novartis, which did not include the use of mandatory primary rash prophylaxis.

The Company believes that the preliminary SEACRAFT-1 data reinforce the potential of the ongoing Phase 3 SEACRAFT-2 trial in patients with NRAS-mutant (NRASm) melanoma. The Company expects to read out randomized dose optimization data from Stage 1 of the SEACRAFT-2 Phase 3 trial in 2025.

On October 24, 2024 Epitopea, a transatlantic cancer immunotherapeutics company developing accessible off-the-shelf RNA-based immunotherapies, reported the closing of a USD $31 million pre-Series A financing (Press release, Epitopea, OCT 24, 2024, View Source [SID1234647364]).

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The pre-Series A financing brings the total capital raised by Epitopea to over USD $45 million. New investors Investissement Québec, adMare BioInnovations and Jonathan Milner join existing investors Advent Life Sciences, CTI Life Sciences, Cambridge Innovation Capital, Fonds de Solidarité FTQ, the Harrington Discovery Institute, IRICoR and Novateur Ventures, all of whom also participated in this financing round.

Dr. Alan C. Rigby, Epitopea’s CEO, said,

"We believe that more durable cancer therapies are needed to transform the lives of cancer patients diagnosed with hard-to-treat solid tumors where overall survival is still poor for most patients. We continue to make significant strides toward the clinic, which has strengthened investor enthusiasm, and resulted in an over-subscribed pre-Series A in support of our forward-looking mission and vision. This additional financing will support strategic pre-clinical discovery in solid tumors of interest while accelerating our near-term clinical development plans for Epitopea’s next generation, tumor selective, off-the-shelf, RNA-based immunotherapies that we believe have the potential to extend the durability of clinical response in patients."

"In this round we would like to warmly welcome new investors Investissement Québec, adMare BioInnovations and Jonathan Milner, whose participation complements the continued passionate support of our existing transatlantic investor syndicate. This pre-Series A raise provides the necessary finances to accelerate our development campaigns and transition to a clinical-stage company with a focused commitment of delivering our transformational RNA cancer immunotherapy into the clinic in 2026".

Satish Jindal, Ph.D., General Partner with Advent Life Sciences added,

"As a founding investor of Epitopea, we are pleased to continue our robust support of the company as it makes major strides in exploiting its proprietary CryptoMapTM platform to identify novel targets that can serve as the basis for the development of a range of ground-breaking cancer immunotherapies. Through our investment in this exciting and growing company, we look forward to Epitopea advancing a first off-the-shelf RNA cancer immunotherapy into the clinic, which could bring significant improvements to cancer patients’ quality and duration of life."

"adMare is thrilled to invest in Epitopea and support the development of their highly differentiated RNA therapeutic platform. Epitopea’s innovative approach to cancer treatment aligns with our mission to drive scientific progress and bring transformative therapies to patients. We look forward supporting the growth of this promising company,"

said Frédéric Lemaître Auger, Vice President Investments at adMare BioInnovations.

"Alongside other key players in the financial ecosystem, Investissement Québec is proud to participate in this round of funding designed to accelerate preclinical stages and research into cancer immunotherapies. Our support will not only promote the development of homegrown expertise in Québec, but also help drive the growth of a promising young Montréal business at the heart of the strategic life-sciences sector".

said Bicha Ngo, President and CEO, Investissement Québec.