PERK

- IMM-1-104 has been well-tolerated, demonstrating the potential for a differentiated safety profile - - 100% suppression of acquired RAS alterations was observed in evaluable patients profiled for ctDNA and treated with IMM-1-104, supporting goal of Universal-RAS activity - - Target lesion regression observed in over half of patients treated with IMM-1-104 at 320mg or 240mg QD, with best individual lesion regression of -35.7% and best RECIST sum of longest diameters (SLD) of -18.9%, both at 320mg - - Candidate RP2D of 320 mg QD supported by tolerability, PK/PD, ctDNA results & initial anti-tumor activity - - Phase 2a portion of the study underway with three monotherapy and two combination arms in earlier lines of treatment, with initial data from multiple arms expected in 2024 - - Immuneering will host an investor call today at 8:30 a.m. ET. - March 14, 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, today announced positive topline results from the ongoing Phase 1 portion of its Phase 1/2a clinical trial of IMM-1-104 in advanced RAS-mutant solid tumors. “Immuneering was founded with the goal of creating medicines for broad populations of cancer patients. In designing IMM-1-104, we sought to challenge the conventional wisdom that the MAPK pathway must be targeted narrowly and inhibited chronically, and that patients must often accept grueling toxicity. Insights from our platform led us to a fundamentally new approach, Deep Cyclic Inhibition, aiming to provide better tolerability and broader, universal-RAS activity,” said Ben Zeskind, Chief Executive Officer of Immuneering. “Today’s results are an important step towards that goal, as we share positive topline data from the Phase 1 portion of our Phase 1/2a clinical trial of IMM-1-104 in advanced RAS-mutant solid tumors. We believe these results demonstrate clear proof of concept, as IMM-1-104 shrank MAPK-dependent lesions in highly aggressive, late-line cancers, prevented acquired alterations in RAS, and has been well-tolerated, showing the potential for a differentiated safety profile.” Ben Zeskind continued, “The endpoints of the Phase 1 portion were to assess the safety and tolerability of IMM-1-104, identify a candidate recommended Phase 2 dose (RP2D), and evaluate pharmacokinetics (PK). As of the data cut-off date of February 20, 2024, the patients in Phase 1 had a dozen different RAS mutations across eight different types of cancer. More than 60% of such patients had pancreatic cancer, more than 80% with available treatment history had never responded to any prior treatment for metastatic disease, and approximately two-thirds received IMM-1-104 in the third-line setting or later, up to seventh-line. IMM-1-104 has been well-tolerated and shown promising initial signs of clinical activity which we believe bodes well for the Phase 2a portion of our study; already underway and expected to enroll patients in earlier lines of treatment whose cancer has had less time to mutate. The Phase 2a portion is studying IMM-1-104 as a single agent and in combination, and could offer the clearest sign yet that IMM-1-104 has the potential to be an effective and universal treatment for RAS-mutant solid tumors. We expect to report initial data from multiple arms of our Phase 2a portion in 2024, and we look forward to sharing that data later this year.” “Preliminary top line data from the Phase 1 portion of this trial with IMM-1-104 provided encouraging initial tumor activity and a well-tolerated safety profile in a refractory patient population,” said Vincent Chung, M.D., FACP, Professor, Department of Medical Oncology & Therapeutics Research at City of Hope, one of the largest cancer research and treatment organizations in the United States, and a principal investigator on this Phase 1/2a clinical study. “City of Hope looks forward to furthering clinical trials testing innovative, potentially lifesaving cancer treatments and will continue to evaluate IMM-1-104 in the Phase 2a portion of the study currently underway.” Topline Results from IMM-1-104 Study Phase 1 Portion Safety and Tolerability Results: As of February 20, 2024 (N=41), IMM-1-104 has been well-tolerated, with the potential for a differentiated safety profile. Among treatment-related adverse events (TRAEs) occurring in greater than 10% of patients, no grade 4 TRAEs were observed, only one grade 3 TRAE was observed (a non-serious rash that was reversible), and a modest number of grade 2 TRAEs were observed in each category. No TRAEs were deemed serious. Deep Cyclic Inhibition Proof of Concept for IMM-1-104: As of February 20, 2024 (N=19), patient plasma data showed IMM-1-104 at 320mg inhibiting phosphorylated extracellular signal-regulated kinase (pERK) at a level of 90% or greater for 2.7 hours, before returning to near-zero levels in advance of 24 hours. IMM-1-104 at a 240mg dose achieved 90% or greater levels of pERK inhibition for 1.9 hours, before returning to near-zero levels in advance of 24 hours. Immuneering evaluated both 240mg and 320mg QD as prospective doses for the Phase 2a portion of its Phase 1/2a study. Based on data from this trial, Immuneering selected a candidate RP2D of 320mg QD. Universal-RAS Proof of Concept for IMM-1-104: As of February 20, 2024 (N=22), 100% of evaluable patients profiled by ctDNA and treated with IMM-1-104 experienced no new acquired alterations in RAS. Excluding two patients treated with IMM-1-104 at 160mg (which Immuneering believes to be a sub-therapeutic dose), no new acquired alterations in MAPK pathway genes were observed, suggesting that there was no mutation in the MAPK pathway that a tumor could use to evade IMM-1-104. Initial Signs of Clinical Activity: While clinical activity was not an endpoint of the Phase 1 portion of the trial, Immuneering believes data generated as of the cutoff date of February 20, 2024 show promising signs for IMM-1-104’s potential clinical activity: 53% of patients had ≥ 1 target lesion(s) regress when treated with IMM-1-104 at either 320mg or 240mg. Best individual lesion regressions were -35.7% at 320mg in second-line setting (vs. -11.4% at 240mg). Best RECIST SLD was -18.9% at 320mg in second-line setting (vs. -7.1% at 240mg). Longest duration on therapy was 162 days (5+ months) at 240mg, with no TRAEs. “With the data from this trial through February 20, 2024, IMM-1-104 demonstrated its potential to induce Deep Cyclic Inhibition, and in doing so has been well tolerated – consistent with what we observed preclinically. We are also pleased with highly encouraging signs of activity observed among advanced RAS-mutant solid tumors,” said Brett Hall, PhD., Chief Scientific Officer of Immuneering. “We have a growing group of enthusiastic investigators and sites who are commencing the Phase 2a trial. Today’s clinical results would not have been possible without the investigators and patients participating in this study, to whom we extend our sincerest thanks, as well as the committed and hard work of my fellow Immuneers.” Immuneering plans to present further data from the ongoing Phase 1 portion of its Phase 1/2a study of IMM-1-104 in advanced RAS-mutant solid tumors at a future medical meeting. Immuneering’s Phase 1 portion of its Phase 1/2a clinical trial is an open-label study designed to evaluate the safety, tolerability, PK and preliminary efficacy of IMM-1-104 in patients with advanced RAS mutant solid tumors. The Phase 1 portion is being conducted at five clinical sites in the United States. Data from the Phase 1 portion led to Immuneering’s candidate RP2D of 320mg for IMM-1-104. The Phase 2a portion is expected to include up to twenty clinical sites and has already dosed its first patient. Near-Term Milestone Expectations IMM-1-104 Initial data from multiple arms of the Phase 2a portion of Immuneering’s Phase 1/2a study of IMM-1-104 expected in 2024. IMM-6-415 First patient in Phase 1/2a trial of IMM-6-415 expected to be dosed in March 2024. IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320). Immuneering is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy. The company aims to achieve universal activity through Deep Cyclic Inhibition of the MAPK pathway, impacting cancer cells while sparing healthy cells. Immuneering’s lead product candidate, IMM-1-104, is an oral, once-daily deep cyclic inhibitor currently in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations. IMM-6-415 is an oral, twice-daily deep cyclic inhibitor being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS or RAF mutations. The company’s development pipeline also includes several early-stage programs. For more information, please visit www.immuneering.com. The content above comes from the network. if any infringement, please contact us to modify.

HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address cancer relapse, metastasis, and resistance, today announced data from a poster presentation at the 65th ASH Annual Meeting and Exposition, which took place from December 9-12th, 2023 in San Diego, California. “Our presentation at ASH builds on our poster presentation earlier this year at the AACR Special Conference in AML and showed the potential of HC-7366, an activator of integrated stress response (ISR) kinase GCN2, in addressing various resistance mechanisms of SOC agents, venetoclax and azacitidine,” said Jonathan Lanfear, President and Chief Executive Officer at HiberCell. “Our data also demonstrated that HC-7366 has monotherapy activity in TP53-mutant preclinical models as well as tumor regressions in models of AML as part of a triplet combination with venetoclax and azacitidine. Both the TP53-mutant and relapsed/refractory, to venetoclax and azacitidine, are settings with poor prognoses for patients and represent major unmet clinical needs. We look forward to providing additional information on our clinical development plans for HC-7366 in AML in 2024.” Presentation Title: Activation of GCN2 by HC-7366 Results in Significant Anti-Tumor Efficacy As Monotherapy and Overcomes Resistance Mechanisms When Combined with Venetoclax in AML Abstract Number, Link: 2943, https://ash.confex.com/ash/2023/webprogram/Paper181245.html HC-7366 potently activates integrated stress response (ISR) signaling via GCN2 and shows single-agent antitumor activity in vivo in TP53-mutant AML CDX models. Genome-wide CRISPR screen demonstrates that HC-7366-treated cells are sensitive to BCL2 inhibition. The combination of HC-7366 and venetoclax shows combination benefit, characterized by enhanced activation of ISR by the doublet and inhibition of several modes of venetoclax resistance. The triplet combination of low-dose HC-7366, venetoclax, and azacitidine is significantly more efficacious than the venetoclax/azacitidine doublet. Importantly, the triplet combination also significantly inhibits the resistance mechanisms, including the anti-apoptotic MCL1 protein, a known mechanism of resistance to venetoclax. Together, these data support the treatment of AML patients with HC-7366 in combination with venetoclax and azacitidine. HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have anti-tumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in models of both solid and liquid tumors. HC-7366 is currently under investigation as monotherapy in Ph1a/1b studies in advanced solid tumors (NCT05121948). HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and anti-tumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse; all significant drivers of cancer-related deaths. Our product candidates HC-5404 and HC-7366, both completing Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently advancing towards Phase 2 clinical development, modulates the anti-tumor innate immune response. For more information about HiberCell, please visit hibercell.com. The content above comes from the network. if any infringement, please contact us to modify.

HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address cancer relapse, metastasis, and resistance, today announced a clinical collaboration with Merck (known as MSD outside the United States and Canada) to evaluate HC-7366, HiberCell’s first-in-class, potent and selective activator of the general control nonderepressible 2 (GCN2) kinase, in combination with WELIREG® (belzutifan), Merck’s oral hypoxia-inducible factor-2α (HIF-2α) inhibitor, for the treatment of clear cell renal cell carcinoma (RCC). The Phase 1b study will evaluate the safety, tolerability, and preliminary efficacy of HC-7366 in combination with WELIREG in participants with ccRCC. With a focus on determining the recommended Phase 2 dose (RP2D), the study includes a dose-escalation phase followed by a dose-expansion phase and an independent HC-7366 monotherapy cohort. The study is planned to open in Q1 2024 and will enroll up to 80 participants at clinical sites across the US. Robert J. Motzer, MD., Section Head, Kidney Cancer, Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center (MSKCC) will be the lead Principal Investigator (PI) for the clinical trial. “We are excited to collaborate with Merck to evaluate HC-7366 in combination with belzutifan,” said Jonathan Lanfear, President & CEO of HiberCell. “We are also excited to announce that one of the scientific leaders within the RCC space, Dr. Robert Motzer, will be our lead PI for this important trial. We expect this study to build on what we have demonstrated preclinically, showing that the combination of these two therapies has the potential to significantly broaden and deepen patient responses relative to belzutifan alone. This trial will also build on the data from our ongoing Ph1a/1b monotherapy studies for HC-7366 in solid tumors. We are eager to pursue this investigational combination in a setting where additional treatment options for patients are needed.” WELIREG® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Clear cell renal cell carcinoma is the most common type of kidney cancer, accounting for ~70% of all cases. Current treatment options for patients include antiangiogenics and immunotherapy, however, there are limited options for patients who are refractory to these therapies. As such, new treatment strategies for patients who have failed immunotherapy and antiangiogenics are urgently needed. HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have anti-tumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in models of both solid and liquid tumors. HC-7366 is currently under investigation as monotherapy in Ph1a/1b studies in advanced solid tumors (NCT05121948). HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and anti-tumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse; all significant drivers of cancer-related deaths. Our product candidates HC-5404 and HC-7366, both completing Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently advancing towards Phase 2 clinical development, modulates the anti-tumor innate immune response. For more information about HiberCell, please visit hibercell.com. The content above comes from the network. if any infringement, please contact us to modify.