On September 30, 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 the publication of its KOMET-001 Phase 1 study manuscript in The Lancet Oncology journal (Press release, Kura Oncology, SEP 30, 2024, View Source [SID1234646927]). The paper, entitled "Ziftomenib in relapsed/refractory acute myeloid leukaemia (KOMET-001): results from an open-label, multi-cohort, phase 1a/1b trial," is now available on The Lancet Oncology website and in the Scientific Manuscripts section on Kura’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The results from the KOMET-001 Phase 1 study are encouraging as they demonstrate meaningful benefit of ziftomenib in NPM1-mutant acute myeloid leukemia (AML), and publication of these data expands the growing evidence supporting the efficacy and safety of ziftomenib in a disease indication of unmet need," said Ghayas C. Issa, M.D., assistant professor of Leukemia at The University of Texas MD Anderson Cancer Center. "We are thankful for the patients and their families for their participation in the KOMET-001 trial and for the scientific community who have contributed to this research to advance more tolerable and effective treatment options for AML patients."

The KOMET-001 study is a Phase 1/2 global, open-label, multi-cohort clinical trial evaluating the safety, tolerability and clinical activity of ziftomenib in relapsed/refractory (R/R) AML. In the Phase 1a dose escalation portion, patients received ziftomenib once daily in 28-day cycles and in the Phase 1b dose validation/expansion portion, patients were randomized to two parallel cohorts at 200 mg and 600 mg. As of the data cutoff on August 30, 2023, 83 patients received one or more doses of ziftomenib and the primary objective of this study was to determine the recommended phase 2 dose (RP2D) based on safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity. The results demonstrated promising clinical activity with manageable toxicity in heavily pretreated patients including marrow blast reduction, neutrophil and platelet recovery, transfusion independence, and clearance of measurable residual disease.

"Our Phase 1 study provided the critical safety and clinical activity data in order to determine the RP2D and support our pivotal Phase 2 registration-directed trial in patients with NPM1-mutant AML," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "These data reinforce our commitment to developing novel investigational therapies, including menin inhibitors, to realize the transformative value for patients with acute leukemias. The clinical data generated to date, including the insights gained from this study, demonstrate the potential for ziftomenib to become a cornerstone of AML therapy through monotherapy and combination approaches."

In May 2024, Kura Oncology announced completion of enrollment in the Phase 2 portion of KOMET-001, a registration-directed trial of ziftomenib in patients with R/R NPM1-mutant AML. Enrollment of the 85 patients in Phase 2 was completed in fewer than 16 months and the Company expects to report topline data from the trial in early 2025.

About NPM1-mutant AML

AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the presence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line, and 3.5 months following the 4th line1. There are currently no FDA-approved therapies targeting NPM1-m AML.

About Ziftomenib

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In the KOMET-001 Phase 1 study, ziftomenib demonstrated encouraging safety and tolerability with reported events consistent with features and manifestations of underlying disease. Clinical activity of ziftomenib as a monotherapy was optimal at the 600 mg daily dose and a 35% complete remission rate was observed in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (600 mg). Ziftomenib has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration for the treatment of R/R NPM1-mutant AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

On September 30, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the company will co-host with the Icahn School of Medicine at Mount Sinai a scientific symposium entitled "Next Generation Immunotherapy Discoveries" (Press release, Innate Pharma, SEP 30, 2024, View Source [SID1234646926]). The symposium will be held in a hybrid format on Thursday, October 3, 2024, from 10:00 a.m. to 5:30 p.m. EDT at the Hess Center for Science and Medicine, New York City and online.
This major scientific event, organized as part of Innate Pharma 25th anniversary, will highlight the latest and greatest advances in immunotherapy and feature key opinion leaders who will share their knowledge and expertise in immunotherapy. Participants will be able to interact with the speakers in a Q&A session after each presentation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Since its inception in 1999, Innate Pharma has been pioneering immuno-oncology, a field which has revolutionized cancer care. As we celebrate 25 years of innovation at Innate Pharma, this is an opportunity to look forward, not only at the broad and diversified pipeline that Innate has generated, but beyond at the next frontiers of immunotherapy. Leading scientists and clinicians will share their perspective at the Next Generation Immunotherapy Discoveries symposium to take place in New York on October 3rd. We thank Mount Sinai hospital for hosting this exciting event." Hervé Brailly, Chief Executive Officer ad interim of Innate Pharma

Confirmed speakers and chairs:
Speakers:
• Lorenzo Falchi, MD, Memorial Sloan Kettering Cancer Center
• Thomas Marron, Ph.D., Icahn School of Medicine at Mount Sinai
• Diane Mathis, Ph.D. Harvard Medical School
• Miriam Merad, MD, Ph.D., Icahn School of Medicine at Mount Sinai
• Pierluigi Porcu, MD, Thomas Jefferson University
• Katy Rezvani MD, Ph.D., MD Anderson Cancer Center
• Antoni Ribas, MD, University of California Los Angeles (UCLA) Jonsson Comprehensive Cancer Center
• Dimitri Skokos, Ph.D., Regeneron
• Eric Vivier, DVM, Ph.D., Innate Pharma and CIML

Chairs:
• Dr. Amir Horowitz, Ph.D. from Icahn School of Medicine at Mount Sinai
• Dr. Joao Monteiro, MD, Ph.D., Nature Medicine

For the full program and registration form of "Next Generation Immunotherapy Discoveries" symposium, please click here.

Prior to the symposium, Innate Pharma will host an Investor and Analyst Meeting from 8:30 a.m. to 9:30 a.m. EDT to provide an overview of the Company’s therapeutic innovations. If you would like to attend, please contact [email protected].

On September 30, 2024 Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully integrated clinical-stage biotech company developing multispecifics in oncology, and Glenmark Pharmaceuticals Ltd., reported a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH) in the United States (Press release, US NCI, SEP 30, 2024, View Source;utm_medium=rss&utm_campaign=igi-announces-crada-with-national-cancer-institute-to-test-proprietary-oral-cbl-b-inhibitor-treatment-in-triple-negative-breast-cancer [SID1234646925]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the CRADA, IGI and NCI will collaborate on evaluating IGI’s proprietary Cbl/b small molecule, GRC 65327. "GRC 65327 is a best-in-class, novel, selective, orally active, Cbl-b inhibitor that demonstrates good in vitro potency, in vivo efficacy and an acceptable non-clinical toxicity profile," said Nagaraj Gowda, PhD, Vice-President, Head of Small Molecule Research at IGI.

In the research covered by the CRADA, NCI will first characterize and then test GRC 65327 in immune-competent models of triple-negative breast cancer (TNBC) with the intent of generating preclinical data to support a clinical trial in late-stage TNBC at NCI. Stan Lipkowitz, M.D., Ph.D., Chief of Women’s Malignancies Branch, Deputy Director of the Center for Cancer Research at the NCI, and his team will build on their substantial achievements in early Cbl/b research that include initially cloning the gene and having identified Cbl/b’s role as a negative regulator of the adaptive immune system.

"Small molecule inhibitors of Cbl/b may enhance adaptive anti-tumor activity by increased signaling through the costimulatory pathway in T cells and innate immunity via enhanced NK cell activity," said Dr. Lipkowitz. "My group will test the novel Cbl/b inhibitor developed by IGI in in vitro, cell-based, and in vivo mammary cancer models to evaluate its activity as Cbl/b inhibitors and modulators of adaptive and innate immune response to breast cancers."

"We believe in the power of collaboration to drive innovation. Partnering with Dr. Lipkowitz and the NCI to advance our scientific understanding of GRC 65327 is expected to speed its potential development in TNBC, a cancer with few effective treatment options for patients," said Cyril Konto, M.D., President, Executive Director and CEO of IGI. "In addition, the work of Dr. Lipkowitz’s laboratory in late-stage TNBC complements the program IGI has developed to advance GRC 65327 in other solid tumors."

About IGI’s GRC 65327–Casitas B-Lineage Lymphoma b (Cbl/b) Program: Casitas B-lineage lymphoma b (Cbl/b) is an E3 ubiquitin ligase that has been identified as a key inhibitor of T and NK cells activation in the absence of CD28 costimulation, regulate immune cells activity in PD-1, CTLA4 and TIGIT positive cells. As an intracellular master regulator, Cbl/b inhibition may lead to robust immune cell activation in immune-suppressed tumor microenvironment and induce strong single-agent activity. A first-in-human clinical trial in patients with relapsed/refractory solid tumor indications is expected to start in early 2025. IGI plans to present the preclinical data package for GRC 65327 at an upcoming scientific conference.

On September 30, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported encouraging interim Phase 2 data from the ongoing Phase 2 study evaluating GRANITE, its individualized neoantigen targeting immunotherapy, in frontline microsatellite stable colorectal cancer (MSS-CRC) (Press release, Gritstone Bio, SEP 30, 2024, View Source [SID1234646924]). The randomized, controlled study is designed to evaluate the clinical benefit of maintenance therapy with GRANITE (GRT-C901/GRT-R902) in combination with immune checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Overall progression-free survival (PFS) data show an encouraging benefit for GRANITE patients (HR=0.79 [95% CI, 0.42-1.50]). As expected, the greatest benefit was observed in the 50% of patients with lower disease burden at study entry, as measured by circulating tumor DNA (ctDNA) at study baseline. (HR=0.62 [95% CI, 0.23-1.70]). Continued follow-up is needed to fully assess GRANITE effects and determine whether a plateau of improved PFS (indicating durable clinical benefit) is achieved. The most recent ctDNA assessments for the 20 patients who remain without disease progression (per RECIST) were supportive of potential benefit from treatment with GRANITE: 12 of 13 GRANITE patients had stable ctDNA titers below the assay limit of quantitation (LOQ); 4 of 7 control patients exhibited the same characteristic.

"We are excited by the potential of GRANITE to extend both progression-free and overall survival in a disease where relentless progression is the rule with existing therapies," said Andrew Allen, MD, PhD, Co-Founder, President & CEO of Gritstone bio. "The field of neoantigen-targeting immunotherapy is evolving rapidly, and the focus is shifting to patients with lower volume disease. Notably, patients with newly diagnosed metastatic disease who have low ctDNA at study entry and thereby relatively low disease burden, could benefit from this type of immunotherapy. Success for immunotherapy typically manifests as an elevated plateau in PFS and overall survival Kaplan-Meier curves, and we may be seeing this in our low disease burden population. We need more time to let these data mature. The most recent ‘low and stable’ ctDNA measurements in most GRANITE patients are encouraging since that pattern is not typically seen in patients about to develop disease progression. The potential PFS benefit observed in MSS-CRC, a notoriously ‘cold’ tumor, suggests opportunity for even greater effects in tumors more typically amenable to immunotherapy."

Dr. Allen continued, "These data support further exploration of GRANITE in frontline MSS-CRC and in other low burden (neo)adjuvant settings. With this new dataset in hand, we continue to actively explore several strategic and funding alternatives to rapidly advance our innovative immunotherapy for the benefit of patients."

Concurrently, Gritstone announced that it has engaged Raymond James as its financial advisor to support the Company in exploring and reviewing potential value-maximizing strategies. Gritstone does not intend to discuss or disclose further developments regarding the exploration of strategic alternatives unless and until its Board of Directors has approved a definitive action or otherwise determined that further disclosure is appropriate or required by law.

Key Findings from Interim Phase 2 Data in Front-Line Metastatic MSS-CRC
Data cut as of August 19, 2024

104 patients were randomized 1:1 in the study: 69 patients (39 GRANITE arm, 30 control arm) are included in the treated analysis below. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with the vast majority (80%) of patients having liver metastases in the treated analysis. Thirty-five patients did not advance to study treatment after oxaliplatin, most commonly due to withdrawing consent (n=15), disease progression (n=8), and other reasons (n=12) (12 in GRANITE arm; 23 in control arm).

Interim data demonstrated an emerging PFS benefit to all GRANITE recipients (study not statistically powered for PFS)
21% relative risk reduction of progression or death with GRANITE vs. standard of care (SOC) control in all treated population (HR=0.79 [95% CI, 0.42-1.50])
33% (13/39) GRANITE and 23% (7/30) of control patients remain on study and free of progression
Last ctDNA assessment is below the assay LOQ in 12/13 GRANITE and 4/7 control patients
Clinical benefit was most notable in patients with low disease burden (defined as patients with ctDNA equal to or below the trial population median value at study entry)
38% relative risk reduction of progression or death with GRANITE vs. SOC control with low ctDNA subgroup (HR=0.62 [95% CI, 0.23-1.70])
Low baseline ctDNA is a likely prognostic and predictive factor

Immune data were consistent with clinical activity

Functional neoantigen-specific T cells were observed in all 16/16 GRANITE patients tested by ELISPOT
Association of PFS and peak ex vivo ELISPOT responses was apparent, suggesting that ex vivo ELISPOT may be a surrogate for PFS

GRANITE demonstrated a favorable safety and tolerability profile

No patients discontinued study treatment due to an adverse event (AE)
Common adverse events were the mild systemic and local effects associated with any potent vaccine, i.e. transient flu-like illness
One treatment-related serious AE (fatigue) occurred in the GRANITE arm (patient continued GRANITE treatment without recurrence upon recovery)
Gritstone plans to review the PFS data with FDA in the coming months and agree on next steps to advance GRANITE, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.

On September 30, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that it and partner Moffitt Cancer Center ("Moffitt") have submitted an amendment to the current protocol that governs its ongoing clinical trial utilizing a CAR-T therapy to treat ovarian cancer (NCT05316129) (Press release, Anixa Biosciences, SEP 30, 2024, https://ir.anixa.com/news/detail/1052/anixa-biosciences-announces-submission-of-protocol-amendment-for-car-t-trial [SID1234646922]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A key change in the protocol provides a second dose of the therapy to patients who might benefit from an additional dose. Previously, Anixa and Moffitt sought and received approval of a single patient IND application to enable a second dose for a single patient who, upon examination of tumor obtained from a biopsy, exhibited cellular infiltration and necrosis, indicating biologic activity of the CAR-T. This amendment will permit all potential patients to receive another leukapheresis and a second dose of CAR-T, without submitting individual INDs for each patient.

Dr. Robert Wenham, Chair of the Gynecologic Oncology Department at Moffitt, and the principal investigator of the trial, stated, "In initial Phase 1 clinical trials, it is customary to begin with low, often subtherapeutic cell doses to verify safety, before increasing the dose levels. In our study, the patient approved for a second dose by the individual IND received the starting, lowest dose. While initially meeting the criteria for progression due to size of her predominate tumor, her cancer has since remained relatively stable and she has not received additional therapy since her first infusion. We are hoping a second, higher dose may improve her overall response and outcome. In general, we anticipate that higher cell doses will lead to efficacy, but for solid tumors, a second dose may be needed in a subset of patients to improve the rate and durability of responses."

"We hope to get approval from regulatory agencies shortly, to enable second doses for the appropriate patients. We are clearly enthusiastic about the progress of this trial and are looking forward to treating additional patients," stated Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences.