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 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 Scientists at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, reported to have collared a tricky culprit that helps cancer cells evade CAR T cell therapy (Press release, City of Hope, DEC 17, 2024, View Source [SID1234649180]).

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CAR T cell therapy harnesses the immune system to seek out and kill tumor cells. This treatment is used in certain types of leukemia and lymphoma — blood cancers. Some wily cancer cells, however, have learned how to hide from the immune system to avoid destruction. The study published today in the journal Cell could lead to more personalized therapies that improve cancer patients’ survival.

The researchers identified a protein called YTHDF2 that plays a starring role in advancing the development of blood cancers. City of Hope then created a new medicinal compound called CCI-38, which targets and suppresses YTHDF2, reducing the growth of aggressive blood cancers. The approach improves the likelihood of successful cancer treatment.

"We believe that using CCI-38 to target YTHDF2 will significantly enhance the effectiveness of CAR T cell therapy on blood cancer cells," said Jianjun Chen, Ph.D., Simms/Mann Family Foundation Chair in Systems Biology and the director of the Center for RNA Biology and Therapeutics at Beckman Research Institute of City of Hope.

"One of the challenges in treating blood cancers is a phenomenon called ‘antigen escape.’ A key target for these therapies is a protein called CD19 found on the cancer cells," added Dr. Chen, corresponding author of the new study.

However, in 28-68% of cases, the cancer cells lower or lose this CD19 marker, making treatments less effective. Although researchers are working on strategies to target multiple components, nearly half of patients are still affected by this issue.

YTHDF2 switches on genes that help cancer cells produce a stable energy source to fuel the cells’ ability to grow and spread. Moreover, this protein helps cancer cells conceal themselves by reducing the presence of antigen biomarkers that normally trigger the immune system to detect and attack cancer. Lastly, excess YTHDF2 works like a werewolf’s bite to transform blood cells from healthy to cancerous in mouse studies.

"Reducing the need for follow-up treatments could lead to better long-term survival and less relapse for our patients while lowering side effects and medical costs," said Xiaolan Deng, Ph.D., an associate research professor in systems biology at Beckman Research Institute of City of Hope and a co-corresponding author of the study.

City of Hope, a recognized leader in CAR T cell therapies for glioblastoma and other cancers, has treated more than 1,600 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world.

"Unraveling the biology underlying YTHDF2’s function will help us develop new strategies to prevent tumor cells from escaping immune surveillance," said Zhen-Hua Chen, Ph.D., a staff scientist in systems biology at Beckman Research Institute of City of Hope and first author of the study. "This could lead to personalized approaches for patients whose blood cancers don’t respond to initial treatment or who relapse after initial response to T cell-based immunotherapy."

The City of Hope team has filed a patent application covering critical aspects of this work, which holds implications for improving care for patients with other cancers and severe autoimmune diseases. The next phase of research will focus on improving CCI-38’s safety and effectiveness, exploring new methods to drive YTHDF2 out of cancer cells, and developing clinical trials.

The Cell study "YTHDF2 promotes ATP synthesis and immune-evasion in B-cell malignancies" was supported by a National Institutes of Health grant (P30CA33572), multiple NIH R01 grants to Dr. Jianjun Chen (CA280389, CA271497, CA243386, CA214965, CA236399 and CA211614), and funding from the Simms/Mann Family Foundation.

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 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."