On December 17, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the Company has been awarded a $9.5 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT) to support the clinical investigation of MT-601 in patients with metastatic pancreatic cancer (Press release, Marker Therapeutics, DEC 17, 2024, View Source [SID1234649159]).

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The CPRIT grant is intended to support the Company’s Phase 1 PANACEA study (clinicaltrials.gov Identifier: NCT06549751) evaluating the safety and tolerability of MT-601, a multi-tumor associated antigen (multiTAA)-specific T cell product, in patients with metastatic pancreatic cancer.

The Company’s lead asset, MT-601, is currently being studied in patients with CD19-CAR relapsed lymphoma as the primary indication (clinicaltrials.gov identifier: NCT05798897). Marker previously reported that one of the Principal Investigators presented preliminary safety and efficacy with sustained objective responses observed in three study participants treated at City of Hope National Medical Center (Press Release, April 8, 2024). MT-601 recognizes multiple targets within six tumor-specific antigens that are highly expressed among different cancer indications. Due to the broad target recognition profile of MT-601, the Company plans to investigate its potential application beyond lymphoma in patients with solid tumors.

The use of MT-601 in solid tumors is supported by preliminary efficacy data of a previous study conducted at Baylor College of Medicine investigating multiTAA-specific T cells in patients with pancreatic cancer who received treatment in conjunction with frontline chemotherapy (Phase 1 Trial in Pancreatic Adenocarcinoma (TACTOPS), June 1, 2020; clinicaltrials.gov identifier: NCT03192462). In this study, the multiTAA-specific T cell product targeted five of the six tumor-antigens used in MT-601. In the 13 patients treated, administration of multiTAA-specific T cells was associated with a favorable safety profile and durable cancer control, including 1 complete response, 3 partial responses and 6 patients with stable disease. Notably, measurable tumor responses were observed in 4 patients, and 9 patients exceeded the median overall survival of historical controls of patients receiving chemotherapy alone.

"We are pleased to receive $9.5 million from CPRIT to explore MT-601 in our Phase 1 study in patients with pancreatic cancer," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "The CPRIT application underwent multiple rounds of review by expert panels, and being awarded this grant underscores the innovation behind our therapy and recognizes the potential impact of our study."

Including this CPRIT grant, the Company has been awarded over $30 million in non-dilutive funding from governmental institutions including FDA, NIH and CPRIT. Most recently, the Company was awarded a $2 million grant from the NIH Small Business Innovation Research (SBIR) program to support the investigation of MT-601 in patients with pancreatic cancer. Together with the $9.5 million from CPRIT, Marker will use these funds to advance MT-601 in pancreatic cancer and anticipates clinical program initiation in 2025.

Dr. Vera added: "Being awarded with a total of $9.5 million from CPRIT and $2 million from the NIH SBIR program to advance our lead asset, MT-601, beyond lymphoma to pancreatic cancer is an important acknowledgement of our work and reflects the reviewers’ confidence in our study. With the support of these highly competitive grants from CPRIT and NIH, we will be able to advance MT-601 in pancreatic cancer without affecting operations in the ongoing study of MT-601 in patients with lymphoma."

On December 17, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported that the first patient has been dosed in the Phase 1/2 trial of its novel ImmTAC candidate, IMC-R117C, targeting PIWIL1 in colorectal and other gastrointestinal cancers (Press release, Immunocore, DEC 17, 2024, View Source [SID1234649158]).

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IMC-R117C is Immunocore’s fifth ImmTAC candidate to enter the clinic. PIWIL1 is overexpressed in multiple malignancies, including colorectal cancer (CRC), and is associated with aggressive tumor growth and poor patient survival.i Despite the development and approval of novel therapeutics, there remains a significant unmet medical need in patients with these cancers, especially in advanced colorectal cancer that is refractory to or has relapsed following standard chemotherapies and targeted therapies.

The Company believes IMC-R117C is the first PIWIL1-targeted immunotherapy and estimates that there are up to 20,000 colorectal cancer patients globally that are positive for both PIWIL1 and HLA-A*02:01.

"We are proud to bring forward the first immunotherapy program to target PIWIL1, through our novel ImmTAC candidate, IMC-R117C," said Mohammed Dar, Senior Vice President, Clinical Development and Chief Medical Officer of Immunocore. "PIWIL1 is expressed across all major subsets of colorectal cancer – including microsatellite-stable CRC, which has historically been insensitive to immunotherapy."

The trial will evaluate the safety and clinical activity of IMC-R117C in HLA-A*02:01-positive patients with select advanced solid tumors. In addition to evaluating IMC-R117C as a single agent, the trial will also test combinations with standards of care.

On December 17, 2024 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, reported that it will hold a virtual Investor Event in early January 2025 to discuss data from its ongoing Phase 2a trial of IMM-1-104 (Press release, Immuneering, DEC 17, 2024, View Source [SID1234649157]).

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Specifically, the company plans to present:

Additional data from IMM-1-104 in combination with mGnP in first-line pancreatic cancer.
Initial data from IMM-1-104 in combination with mFFX in first-line pancreatic cancer.
Initial data from IMM-1-104 monotherapy in second-line pancreatic cancer.
In addition, the company will provide initial PK, PD and safety data from the Phase 1 portion of the company’s Phase 1/2a trial of IMM-6-415.
Details of how to access the Investor Event will be provided in due course.

"We are excited to soon share additional data from our Phase 2a study of IMM-1-104 in patients with pancreatic cancer," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "Pancreatic cancer patients urgently need new options that enable them to live longer and feel better. The FDA has recently granted IMM-1-104 Orphan Drug designation in pancreatic cancer, along with Fast Track designations in first and second-line pancreatic cancer, and advanced melanoma. We look forward to building on our September update with additional data from the Phase 2a study of IMM-1-104."

On December 17, 2024 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported updated clinical data from the ongoing AFM24-102 trial of AFM24/atezolizumab combination therapy in heavily pretreated NSCLC patients (Press release, Affimed, DEC 17, 2024, View Source [SID1234649156]). Results continue to demonstrate meaningful clinical activity in both NSCLC EGFRwt and EGFRmut patients with good tolerability. In addition, the Company reported findings from a post-hoc exposure-response analysis in patients treated with 480 mg AFM24 showing higher AFM24 exposure is associated with significantly better response rates, improved PFS and overall survival (OS). Based on these data, the future development program for AFM24 will use a dose of 720 mg weekly, a dose that has already been successfully tested in the phase 1 study of AFM24 showing a manageable safety profile.

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"With the compelling data from both EGFR wild-type and mutant cohorts, along with the exposure-response analysis we are unlocking the possibilities for the AFM24/atezolizumab combination in treating heavily pretreated NSCLC patients," said Dr. Shawn Leland, PharmD, RPh, Chief Executive Officer of Affimed. "These findings highlight our opportunity to further refine and advance this treatment with a clear focus on patients who stand to benefit the most. We are excited about the path ahead and are committed to exploring innovative strategies to bring this promising therapy to those in need."

NSCLC EGFR Wild-type Cohort Update

Patient population: As of the November 14, 2024 data cut, there were 43 patients in the full analysis set (FAS) and 33 patients in the per protocol set (PPS), defined as having one post baseline scan according to RECIST. Reasons for non-evaluability were early symptomatic deterioration (6), non-related AEs (2), too early (2). Patients had a median of 2 prior lines of therapy (range: 1–7). All patients had received platinum-based combinations and PD(L) 1 targeting checkpoint inhibitors (CPIs), and two-thirds had received taxanes. Importantly, all but one patient discontinued their previous CPI because of progression.

Safety: The AFM24 and atezolizumab combination therapy was well tolerated with no unexpected safety findings. Infusion related reactions (IRRs) were the most common adverse event (AE) reported, in 54% of patients; IRRs were manageable, mostly present during the first infusion, and fully resolved. Elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), a known side effect of atezolizumab, were reported in 21% and 16% of patients respectively.

Anti-tumor activity and durability (N=33, PPS): The combination demonstrated an ORR of 21% (7 responses: 1 complete response (CR), 5 partial responses (PR) and 1 additional not yet confirmed PR), tumor shrinkage in 48% of patients (16/33 patients) and a DCR of 76%. In the 7 responders, 5 had never achieved an objective response on prior CPIs and only 2 patients had a PR on previous CPI containing treatment (both to a triplet of platinum, pemetrexed and CPI). The preliminary median PFS is 5.6 months, and 36% of patients are currently on treatment.

NSCLC EGFR Mutant Cohort Update

Patient population: As of the November 14, 2024 data cut, 28 patients were in the FAS (reasons for non-evaluability at the cut-off were: ongoing with no scan yet 5, early deterioration 4, non-related AEs 2), with updated results presented for the first 17 patients in the PPS. All patients had received prior EGFR specific TKI therapy, and 77% had received platinum-based chemotherapy.

Anti-tumor activity and durability (N=17, PPS): AFM24 combined with atezolizumab showed promising activity in refractory NSCLC EGFRmut patients achieving an ORR of 24% (4 confirmed responses: 1 CR, 3 PRs), a DCR of 71% and tumor shrinkage in 41% of patients. With a median follow-up of 9 months, the median PFS was 5.6 months. Five (29%) patients are on treatment for over 10 months, demonstrating long term tumor control.

Post-Hoc Exposure-Response Analysis

Analysis process: A post-hoc exposure-response analysis was conducted including NSCLC EGFRwt and EGFRmut subjects (n= 44) treated with 480 mg AFM24 in both the AFM24-101 monotherapy study or the AFM24-102 AFM24 combination with atezolizumab study. Low and high exposure groups were calculated using a median cut-point of patient`s mean trough values.

Safety, anti-tumor activity and durability: Baseline characteristics were balanced between the high and low exposure groups and there were no differences in body mass index or percentage of administered dose that would explain differences in exposure. The high exposure group showed an ORR of 46% and a PFS of 7.4. A sensitivity analysis using quartiles of exposure supported a clear relationship between exposure and outcome indicating that higher doses of AFM24 will likely result in improved efficacy. The PK profile of 720 mg AFM24 weekly, as tested successfully in the phase 1 trial and further pharmacokinetic modelling indicate that 720 mg will achieve exposure levels that are equal or above the plasma concentrations observed for the high exposure group.

"Advanced-stage NSCLC remains one of the most challenging cancers to treat, and our findings bring new hope," said Dr. Andreas Harstrick, MD, Chief Medical Officer of Affimed. "We see compelling efficacy results with the AFM24/atezolizumab combination in heavily pretreated NSCLC patients, independent from the mutational status. The results are remarkable as we achieve this with a purely immunotherapy-based approach in patients that are often not able or not willing to take additional toxic therapies. The insights in the relation of exposure and efficacy will allow us to further improve on the efficacy and provide a clear path forward as we strive to unlock new possibilities for EGFR NSCLC patients."

About AFM24

AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

On December 17, 2024 Actuate Therapeutics, Inc. (NASDAQ: ACTU) ("Actuate" or the "Company"), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), reported new positive data from its ongoing and fully enrolled randomized Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) (Actuate-1801 Part 3B) (Press release, Actuate Therapeutics, DEC 17, 2024, View Source [SID1234649155]).

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A pre-specified analysis was triggered by reaching >70% death events in the GnP control arm (data cut off November 15, 2024). The analysis of interim data demonstrated treatment with elraglusib in combination with GnP resulted in statistically significant increases in 1-year survival rate (p value of 0.002) and median overall survival (p value of 0.016, hazard ratio of 0.63) versus treatment with GnP alone. The combination treatment also resulted in increased Objective Response Rates (ORR) and Disease Control Rates (DCR) in the elraglusib/GnP combination arm versus the GnP control arm.

"These interim results are highly encouraging and underscore the transformative potential of elraglusib in the treatment of metastatic pancreatic cancer," said Daniel Schmitt, President & Chief Executive Officer of Actuate. "The improvement in median and overall long-term survival, disease control rate and overall response rate compared to GnP alone, combined with elraglusib’s favorable risk-benefit profile, offers the possibility of improved outcomes for patients with limited treatment alternatives. We are excited to continue evaluating the potential of elraglusib, a novel immune-oncology GSK-3 targeted approach for mPDAC, and look forward to engaging with the FDA in 1H 2025 to share topline data and discuss next steps, including a proposed phase 3 registration trial.

Inhibition of GSK-3β may inhibit tumor growth and improve survival through several complimentary mechanisms that include enhancement of chemotherapy activity, activation of innate anti-tumor immunity and regulation of gene expression, leading to alterations in tumor metabolism and Epithelial-to-Mesenchymal Transition (EMT).

Study highlights include:

· The interim data met the trial primary endpoint with a 1-year survival rate of 43.6% in the elraglusib-GnP combination arm versus 22.5% in the GnP control arm (p=0.002);
o Eighteen and twenty-four month survival rates also demonstrated benefit of 20.9% vs 0% and 16.7% vs 0% in the elraglusib-GnP combination vs GnP arms, respectively.
· As of the November 15, 2024 cutoff, 38% of subjects were still alive in the elraglusib-GnP combination arm vs 19% in the GnP control arm.
· A statistically significant 37% reduction in risk of death and increased median overall survival were observed in the elraglusib-GnP combination arm (mOS 9.3 months) vs the GnP control arm (mOS 7.2 months), (HR=0.63 p=0.016).
· The trial also met its primary safety endpoint. Treatment-emergent adverse events (TEAEs) and Serious Adverse Events (SAEs) in the elraglusib-GnP combination arm were similar to those observed in the GnP arm, indicating a favorable risk-benefit profile for the elraglusib-GnP combination.
· At the interim cutoff of November 15, 2024, the ORR was 27.7%, DCR was 42.6 %, and PFS was 5.6 months in the elraglusib-GnP combination arm versus 20.5%, 33.3% and 4.9 months in the GnP arm, respectively.
· To date, there have been 2 patients in the elraglusib/GnP combination arm with previously inoperable metastatic lesions with noted reductions in target lesions and referred for successful resection, 1 of which resulted in 100% reduction in total tumor burden after surgery. In addition, there have been 1 Complete Response and 1 Partial Response with 100% reduction in target lesions in the elraglusib GnP combination arm versus 0 in the control arm to date.

"Pancreatic cancer is one of the most aggressive and lethal cancers with less than 5% survival rate in the US at 5 years. We are encouraged by consistent evidence of significant clinical benefit and anti-tumor activity in the elraglusib combination arm across multiple endpoints in this study," said Dr. Andrew Mazar, Actuate’s Scientific Co-Founder and Chief Operating Officer. "Further, the favorable risk-benefit profile observed to date may provide a treatment option for many patients with metastatic pancreatic cancer that may not tolerate more aggressive and less tolerable chemotherapy approaches."

The ongoing Actuate-1801 Part 3B study (NCT03678883) is a randomized, controlled Phase 2 trial of elraglusib with GnP versus GnP alone in first line mPDAC. The trial enrolled 286 mPDAC patients with no prior systemic treatment for metastatic disease, who were randomized 2:1 to the elraglusib treatment arm (elraglusib + GnP) or the control arm (GnP alone). Elraglusib is administered at a dose of 9.3 mg/kg by IV infusion on Day 1 of each week of a 28-day cycle. The primary endpoint is 1-year survival rate, with mOS the primary parameter for summarization of survival data at the end of the study. Secondary endpoints are DCR, ORR, PFS and AE.