Melanoma-Pancreatic Cancer Syndrome

With the Response Rate increasing to 23%, MDNA11 continues to show compelling single-agent activity in the ABILITY-1 study amongst high-dose phase-2 eligible patients (N=13) that failed checkpoint inhibitor therapies, while maintaining an acceptable safety pro > Tumor shrinkage was also observed in all high-dose phase-2 eligible patients with stable disease (SD). In addition to a new PR, the clinical benefit rate (PR plus SD for over 24 weeks) and tumor control rate (PR plus all SD) increased to 46% and 69%, respectively First patient was dosed in Phase 1 combination escalation portion of the ABILITY Study evaluating MDNA11 with KEYTRUDA® (pembrolizumab) Additional monotherapy data updates and preliminary combination escalation and expansion data to be shared in H1 and H2 of 2024 Cash runway extended through multiple data readouts and into Q2 of calendar 2025 TORONTO and HOUSTON, Feb. 14, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”)(TSX: MDNA, OTCQB: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, today announced financial results and corporate highlights for the third quarter of fiscal 2024, ended December 31, 2023, and outlined its strategic outlook for 2024. “We are off to a solid start in 2024 with further validation of single-agent anti-tumor activity of our IL-2 super-agonist, MDNA11, in the ABILITY-1 study,” said Dr. Fahar Merchant, President and CEO of Medicenna. “We are encouraged by another PR, increasing the total number of PRs to 3 in patients with prior failure from immune checkpoint therapy. With response rates above 20% at this early stage of the trial in high-dose phase-2 eligible patients, we believe that MDNA11’s differentiated mechanism demonstrates its clinical superiority to competing IL-2 programs. This is especially gratifying in view of the desirable safety, pharmacokinetic and pharmacodynamic characteristics observed to date. We look forward to reporting additional monotherapy dose expansion and combination escalation and expansion data from the ABILITY-1 study during H1 and H2 2024.” Dr. Merchant continued, “We believe 2024 will be a transformational year for Medicenna as we continue advancing our mid- and late-stage MDNA11 and bizaxofusp assets for patients battling difficult to treat cancers. The global multi-arm Phase 1/2 ABILITY-1 study is expanding to various cancer centers in the US, Canada, Australia, South Korea and Europe evaluating MDNA11 as a single-agent and in combination with KEYTRUDA® in patients with advanced solid tumors. For bizaxofusp, we plan to seek Breakthrough Therapy Designation from the FDA, in addition to securing alignment with the EMA for the Phase 3 trial design supported by the FDA. These endeavors will further enhance potential partnership activities for bizaxofusp. We are excited for the year ahead and are increasingly confident about the significant potential of our evolutionary cytokines and delivering on our mission to bring revolutionary medicines to patients.” PROGRAM AND BUSINESS UPDATE: Highlights for the three months ended December 31, 2023, along with recent developments include: MDNA11 New additional iPR in the monotherapy dose expansion portion of the MDNA11 ABILITY-1 Study. Today, the Company reports promising clinical data from the on-going monotherapy escalation and expansion arms of the ABILITY-1 study. In addition to previously announced tumor response data, a third patient in the study has also shown a partial response (PR). A melanoma patient with iPR (PR as per iRECIST) showed pseudo-progression (at week 8) with a PR (at week 12). Response rate exceeds 20% in immune checkpoint failed patients. Amongst 13 patients, all having previously failed or resistant to immune checkpoint inhibitors ("ICI"), receiving high doses of MDNA11 (≥60 µg/kg) with tumor types being evaluated in the monotherapy expansion cohort, the response rate, clinical benefit rate and tumor control rate increased to 23% (3 partial responses), 46% (3 PRs and 3 patients with SD for ≥ 24 weeks) and 69% (3 PRs and 6 SDs), respectively, with shrinkage of target lesions in all patients with SD. Dosed first patient in the combination arm of the ABILITY-1 study. On February 13, 2024, the Company announced that it had dosed the first patient in the combination arm of the ABILITY-1 clinical trial, evaluating potential synergistic effect of MDNA11 when administered with KEYTRUDA® (pembrolizumab). The study will evaluate the safety, tolerability, recommended combination dose for expansion ("cRDE") and therapeutic activity of MDNA11 when combined with KEYTRUDA® in the dose-escalation and dose-expansion arms of the clinical trial. Presented positive MDNA11 monotherapy data at SITC 2023. On November 6, 2023, Medicenna announced encouraging single-agent activity from the dose escalation and evaluation portion of the ABILITY-1 study in advanced cancer patients receiving MDNA11 at doses of ≥60 µg/kg (N = 15) who had previously failed ICI therapies. The results included ongoing partial responses with 100% and 70% reduction of target lesions in pancreatic and melanoma cancer patients, respectively, in addition to durable stable disease in 3 melanoma patients (> 20 to 80 weeks). This data was presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer ("SITC") held in San Diego. On October 25, 2023, Medicenna announced dosing of the first patient in the Phase 2 monotherapy dose expansion portion of the ABILITY-1 Study. Bizaxofusp (MDNA55) Single treatment with bizaxofusp increased median overall survival (mOS) by 100%. On November 17, 2023, the Company announced a poster presentation and an oral summary at the Annual Meeting of the Society of Neuro-Oncology (SNO) highlighting longer term follow up results from the Phase 2b clinical trial of bizaxofusp in patients with recurrent glioblastoma (rGBM). The data demonstrated that a single treatment with bizaxofusp increased median overall survival (mOS) by 100% (14.5 vs. 7.2 months) when compared to a propensity matched external control arm (ECA) irrespective of IL-4R (interleukin-4 receptor) expression and defined as the Phase 3 population. Overall survival (OS) for bizaxofusp-treated patients increased by 370% at Year 1 (62.5% vs 16.7%) and by more than 50% at Year 2 (25% vs 16.1%) when compared to the ECA. No systemic or clinically significant laboratory abnormalities were reported. Treatment-related adverse events were primarily neurological or aggravation of pre-existing neurological deficits due to rGBM. Potential for Breakthrough Therapy Designation (BTD) for bizaxofusp. With compelling longer term survival benefit with bizaxofusp in rGBM patients, as presented at the SNO meeting held in November 2023, Medicenna will seek to apply for BTD with the FDA. Seek alignment with the European Medicines Agency (“EMA”) for the Phase 3 registration trial of bizaxofusp incorporating an ECA and developed with the support of FDA. The proposed Phase 3 trial design incorporating a hybrid external control arm has been supported by the FDA. Medicenna is currently working toward securing alignment with the EMA thereby enabling data from a single Phase 3 registrational trial being sufficient to approval in the EU and USA. Other Pipeline Programs On November 3, 2023, the Company presented preclinical data on its first-in-class IL-13Rα2 targeted candidate, MDNA113, from its T-MASKTM platform, which specifically delivers a masked bispecific anti-PD1-IL2 Superkine to IL-13Rα2 expressing tumors (affecting over 2 million cancer patients annually) where it is activated by cancer specific enzymes. This data was presented at the 38th Annual Meeting of the SITC held in San Diego. On October 3, 2023, new preclinical data characterizing MDNA223, an anti-PD1-IL-2 BiSKIT (Bifunctional SuperKine for ImmunoTherapy), including its synergy when combined with STING agonists were presented at the 2023 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy, held in Toronto, Canada. Corporate Highlights Transition of CMO to consultant role - Dr. Humphrey Gardner has transitioned from Chief Medical Officer to a consulting role. Dr. Arash Yavari, Chair of Medicenna’s Development Advisory Committee, will henceforth lead the clinical activities as Director of Clinical Strategy. Appointment of new CFO – David Hyman has been appointed as Chief Financial Officer of the Company. David Hyman, CA, CBV is an experienced financial professional with over 25 years of experience spanning public practice, capital markets, private equity and industry. For the past five years, Mr. Hyman has provided fractional and full time CFO services to multiple public and private companies, including two early-stage pharmaceutical companies. Appointment of new Auditor – On January 12, 2024, the Company announced that its Board of Directors approved the appointment of MNP LP as the auditor of the Company. OTCQB Listing - On December 19, 2023, the Company announced the commencement of trading on the OTCQB Venture Market in the United States. NASDAQ delisting - On October 27, 2023, Medicenna announced that it was delisted from the Nasdaq as the Company did not meet the listing requirements and that it was reducing its presence in the US to conserve cash. The Company's common shares continue to trade on the Toronto Stock Exchange. Expected Upcoming Milestones Preliminary monotherapy and dose expansion data of MDNA11’s ABILITY-1 study, to be presented at medical conferences in H1 and H2 of 2024. Clinical update from the combination arm of the ABILITY-1 study evaluating MDNA11 in with KEYTRUDA® expected in H1 and H2 of 2024. Financial Results As of December 31, 2023, cash and cash equivalents were $21.8 million, compared to $25.7 million on September 30, 2023. Net loss for the quarter ended December 31, 2023, was $5.0 million or ($0.07) per share compared to a net loss of $1.1 million or ($0.02) per share for the quarter ended December 31, 2022. The increase was primarily a result of a reduction in the non-cash gain related to the change in valuation of the Company’s derivative warrant liability. Research and development expenses of $3.0 million were incurred during the quarter ended December 31, 2023, compared with $2.9 million incurred in the quarter ended December 31, 2022. Higher clinical costs associated with the MDNA11 ABILITY-1 study relative to the prior year quarter were mostly offset by reductions in stock-based compensation and licensing fees. General and administrative expenses of $1.8 million were incurred during the quarter ended December 31, 2023, compared with $2.0 million during the quarter ended December 31, 2022. The decrease in general and administrative expenses in the current quarter is primarily related to a reduction in directors’ and officers’ liability insurance premiums. Medicenna’s interim consolidated financial statements for the three and nine months ended December 31, 2023, and the related management’s discussion and analysis (MD&A) are available on SEDAR+ at and EDGAR. About Medicenna Therapeutics Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first-in-class empowered superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit , and follow us on Twitter and LinkedIn. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Forward-Looking Statements This news release contains forward-looking statements within the meaning of applicable securities laws that relate to the future operations of the Company, plans and projections and other statements that are not historical facts, including, without limitation, statements on the Company’s cash runway, clinical development activities, clinical potential, safety profiles and upcoming milestones and data reporting, including with respect to MDNA11, the ABILITY study and its expansion, bizaxofusp (MDNA55), MDNA113, MDNA223, partnership activities and opportunities and strategic outlook. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest Annual Report on Form 20-F of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. Investor and Media Contact: Christina Cameron Investor Relations, Medicenna Therapeutics ir@medicenna.com (647) 953-0673

Cash runway extended through multiple data readouts and into Q1 of calendar 2025 MDNA11 is generally well tolerated and continues to demonstrate encouraging single-agent activity from Phase 1 portion of the ABILITY-1 Study including 100% and 70% reduction of target lesions in pancreatic and melanoma cancer patients, respectively Four-year follow-up survival results from Phase 2b bizaxofusp (MDNA55) study in patients with recurrent glioblastoma selected for presentation at SNO 2023 on November 17, 2023 TORONTO and HOUSTON, Nov. 14, 2023 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA; OTC: MDNAF), a clinical-stage company focused on the design and development of novel evolutionary superkines to create revolutionary immunotherapies, today announced financial results and corporate highlights for the second quarter of fiscal 2024, ended September 30, 2023. “We are pleased that our cash runway now extends through multiple data readouts in mid-2024 and into the first quarter of 2025, which provides potential opportunities for additional milestones across our programs.” said Fahar Merchant, Ph.D., President, and Chief Executive Officer of Medicenna. “At SITC 2023, we shared positive clinical data readouts for MDNA11. The Phase 1 dose escalation data from the ABILITY-1 study demonstrated that MDNA11 is generally well tolerated and results in durable single-agent activity, including deep ongoing responses with 100% reduction of target lesions in a pancreatic cancer patient and 70% reduction of target lesion in a melanoma cancer patient. This week at SNO 2023, we will be reporting 4-year follow-up survival data from the Phase 2b bizaxofusp study in patients with recurrent glioblastoma, a uniformly fatal form of brain cancer.” “Another key achievement from the period was dosing the first patient in the Phase 2 dose expansion monotherapy arm of the ABILITY-1 study. In addition, we expect to commence the combination portion of the ABILITY-1 study before the end of this year evaluating MDNA11 with pembrolizumab (Keytruda®). We look forward to reporting initial Phase 2 dose expansion data from both the monotherapy and combination arms during the first half of 2024,” concluded Dr. Merchant. Pipeline Highlights MDNA11 Reported updated Phase 1 MDNA11 dose escalation data at SITC 2023. In early November 2023, Medicenna reported encouraging single-agent activity from the dose escalation and evaluation portion of the ABILITY-1 study in advanced cancer patients receiving doses ≥60 μg/kg of MDNA11 (N=15) and who had previously failed immune check-point inhibitor therapies. The results included ongoing partial responses with 100% and 70% reduction of target lesions in pancreatic and melanoma cancer patients, respectively, in addition to durable stable disease in 3 melanoma patients (>20 to 80 weeks).Dosed first patient in Phase 2 monotherapy arm. In October 2023, Medicenna dosed the first patient in the Phase 2 monotherapy dose expansion portion of the Phase 1/2 ABILITY study evaluating MDNA11 in patients with advanced melanoma, non-melanoma skin cancer or microsatellite instability (MSI)-high or mismatch repair (MMR) deficient cancers. Up to 40 patients are expected to be enrolled and administered MDNA11 (90 µg/kg intravenously [IV] Q2W). The Company expects to report initial data from the monotherapy arm in the first half of 2024. Bizaxofusp (MDNA55) Presenting 4-Year Follow-up overall survival data from Phase 2b bizaxofusp study. A poster presentation and an oral summary highlighting long-term follow up from the Phase 2b clinical trial of bizaxofusp (formerly known as MDNA55) in patients with recurrent glioblastoma (rGBM), the Company’s first-in-class IL-4R targeted therapy, will be presented at the Society for Neuro-Oncology (SNO) 2023 Annual Meeting, to be held from November 15-19, 2023, in Vancouver, Canada.Exploring partnerships to fund pivotal study. Following the print publication of the Phase 2b clinical results in the June 2023 issue of the journal Neuro-Oncology, where bizaxofusp demonstrated a doubling of survival versus standard of care in patients with rGBM, Medicenna has embarked on a comprehensive effort to explore partnership opportunities for a Phase 3 registration trial. Other Pipeline Programs Presented preclinical data for MDNA113 at SITC 2023. Medicenna presented preclinical data for MDNA113, a first-in-class IL-13R⍺2 targeted therapy that delivers a masked bi-specific IL-2-anti-PD1 Superkine to the tumor micro-environment. The data demonstrated proof-of-concept for the Company’s novel T-MASK (Targeted Metalloprotease Activated SuperKine) platform technology. The data showed reduced IL-2R agonism with no change to PD1/PDL-1 blockade and reduced systemic lymphocyte expansion providing evidence of dampening of systemic activity. In addition, the preclinical data showed that cleavage of MDNA113 by tumor associated metalloproteases restores IL-2R signaling and that MDNA113 is as effective as non-masked MDNA223 (a bispecific antiPD1-IL-2 superkine) in tumor models.Presented preclinical data for MDNA223 at AACR’s Special Conference in Cancer Research: Tumor Immunology and Immunotherapy. Medicenna presented new preclinical data on MDNA223, a fusion of MDNA11 combined with an anti-PD1 antibody, that is designed to maximize anti-tumor response by concurrently facilitating IL-2R pathway stimulation and PD1 checkpoint blockade on the same effector immune cell. The data support the potential of Medicenna’s superkine-focused platform to create novel therapies for challenging-to-treat ‘cold’ tumors.Strengthened intellectual property portfolio. Medicenna received a U.S. patent for the use of Interleukin-2 Superkine fusion proteins in oncology. This patent strengthens the Company’s intellectual property around its BiSKIT (Bifunctional SuperKine for ImmunoTherapy) platform. Corporate and Financial Highlights Management changes. Key new leadership team appointments include Humphrey Gardner, M.D., as Chief Medical Officer and Arash Yavari, M.D., DPhil, as Chair of the Development Advisory Committee.Delisted from Nasdaq Capital Market. Medicenna’s common stock ceased trading on Nasdaq on November 2, 2023. The Company anticipates significant financial savings as a result of this decision. The Company has applied to have its common shares traded on the OTC Markets. Medicenna’s common stock continues to trade on the Toronto Stock Exchange (TSX). Expected Upcoming Milestones Report 4-year follow-up survival data from the Phase 2b bizaxofusp study in patients with rGBM at the SNO conference to be held from 15-19 November, 2023Commence the combination arm of the ABILITY study evaluating MDNA11 with pembrolizumab (KEYTRUDA®) e.Clinical update from the ABILITY study’s MDNA11 Phase 2 monotherapy arm expected in the first half of 2024.Clinical update from the ABILITY study’s MDNA11 plus pembrolizumab Phase 2 combination arm expected in the first half of 2024. Financial Results As of September 30, 2023, cash and cash equivalents were $25.7 million, compared to $29.6 million on June 30, 2023. Net loss for the quarter ended September 30, 2023, was $3.7 million or $(0.05) per share compared to a net loss of $0.9 million or ($0.01) per share for the quarter ended September 30, 2022. The increase in net loss for the quarter ended September 30, 2023, compared with the quarter ended September 30, 2022, was primarily a result of increased research and development expenditures related to the clinical costs associated with the MDNA11 ABILITY-1 study, and increased licensing and patent legal fees. Research and development expenses of $3.1 million were incurred during the quarter ended September 30, 2023, compared with $2.4 million incurred in the quarter ended September 30, 2022. The increase in R&D expenses for the quarter ended September 30, 2023 was primarily attributable to increased licensing and patent legal fees related to timing as well as intellectual property activities in the current year quarter, higher clinical costs related to the MDNA11 ABILITY study in the current year period, and increased salaries and benefits due to increase in headcount to support the MDNA11 ABILITY-1 study. General and administrative expenses of $2.3 million were incurred during the quarter ended September 30, 2023, compared with $2.4 million during the quarter ended September 30, 2022. The decrease in G&A expenses was primarily attributable to an increase in public company expenses, and salaries and benefits due to increase in headcount, partially offset by the one-time transaction costs associated with warrant derivative in the six month period ended September, 30, 2022 only. About Medicenna Therapeutics Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class class-empowered superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage BiSKITs™ program (Bifunctional SuperKine ImmunoTherapies) is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit https://www.medicenna.com/. Forward-Looking Statements This news release contains forward-looking statements within the meaning of applicable securities laws that relate to the future operations of the Company, plans and projections and other statements that are not historical facts, including, without limitation, statements on the Company’s cash runway, clinical development activities, potential, safety profiles and upcoming milestones and data reporting, including with respect to MDNA11, MDNA113, MDNA223, the Superkine platform, notably MDNA55, partnership opportunities, patent protection and cost savings related to NASDAQ delisting. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest Annual Information Form and Annual Report on Form 20-F of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada and the United States. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. Investor and Media Contacts Christina CameronInvestor Relations, Medicenna Therapeuticsir@medicenna.com Argot PartnersPhone: 212-600-1902medicenna@argotpartners.com

Data presented at AACR Annual Meeting support IMM-1-104's potential to address a broad population of patients with RAS mutant tumors IMM-1-104 well tolerated with no dose limiting toxicities (DLTs) or serious adverse events (SAEs) observed First demonstration of novel deep cyclic inhibition mechanism in humans, with IMM-1-104 achieving significant levels of PK Cmax and a half-life of approximately two hours as predicted Pharmacodynamic data support potential to evaluate preliminary efficacy sooner than expected Study timeline accelerated: recommended Phase 2 dose (RP2D) now expected in early 2024 Investor call to be held today at 9.00 a.m. ET CAMBRIDGE, Mass., April 18, 2023 (GLOBE NEWSWIRE) -- Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company developing medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy, announced positive initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data from the Phase 1 trial of IMM-1-104 (NCT05585320), which are being shared today in a poster presentation titled “Humanized 3D tumor models that are mutationally aligned with AACR GENIE patients predict IMM-1-104 activity in RAS-addicted tumors” (abstract #4265) at the American Association for Cancer Research (AACR) annual meeting. “We are very pleased to share initial PK, PD and safety data from our Phase 1 trial of IMM-1-104 in patients with advanced RAS mutant solid tumors, ahead of schedule,” said Ben Zeskind, Ph.D., MBA, Co-founder, and Chief Executive Officer of Immuneering. “We believe these data from the first patients dosed in our study demonstrate the PK, PD and safety pro for deep cyclic inhibition – the proprietary and novel mechanism through which our therapies are designed to selectively impact cancer cells to a greater extent than healthy cells, regardless of the specific RAS mutation driving the tumor. The data show that we were able to reach significant levels of PK Cmax with the aim of breaking tumor addiction to the MAPK pathway, then rapidly clearing out drug with IMM-1-104’s short half-life. These results position us to accelerate the dose escalation portion of our study, reaching potentially therapeutic levels of IMM-1-104 earlier than previously planned.” “These initial PK and PD Phase 1 data with IMM-1-104 mark a major milestone for Immuneering, and for patients affected by RAS mutant tumors. It is the first time IMM-1-104 has shown the pro believe is necessary for deep cyclic inhibition in humans. Prior therapies have often suffered from steep increases in drug half-life in humans when compared to preclinical models. In contrast, initial clinical results for IMM-1-104 are in line with our preclinical modeling, which we believe helps to de-risk an important element of our universal-RAS program,” said Brett Hall, Ph.D., Chief Scientific Officer of Immuneering. “With today’s results showing an approximate two-hour half-life coupled with reaching target Cmax values faster than expected plus encouraging pharmacodynamic, safety and tolerability results observed, we are accelerating the remaining dose-escalation portion of our trial. We now have an opportunity to assess potential preliminary efficacy earlier than anticipated.” “We are highly encouraged by the initial safety and tolerability data generated to date. IMM-1-104 has been well tolerated with no DLTs or SAEs observed,” said Scott Barrett, M.D., Chief Medical Officer of Immuneering. “We are grateful to the patients participating in our trial, and to the investigators. Investigator enthusiasm remains high, which combined with our study’s broad inclusion criteria, gives us confidence in our ability to keep enrolling patients in an expeditious manner.” The 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 of the study, which is being conducted at five clinical sites in the United States, is evaluating IMM-1-104 following a Bayesian mTPI-2 escalation design, which includes a dose escalation phase and dose evaluation phase to establish an optimized RP2D candidate. Following selection of the RP2D candidate, the Company expects to conduct a Phase 2a dose expansion phase to assess the safety and efficacy of IMM-1-104 at the RP2D in RAS mutated pancreatic, melanoma, lung and colorectal cancers. Highlights of the initial IMM-1-104 Phase 1 PK, PD and safety data presented at AACR include (as of data cut-off date of April 10, 2023, including patients with pancreatic and colon cancer): Significant PK Cmax levels (plasma concentration of therapy in a specific area of the body) observed with IMM-1-104 of over 2,000 ng/mL (or approximately 1 uM drug free-fraction at 160 mg once daily oral dose) Greater than 90 percent PD inhibition of phosphorylated extracellular signal-regulated kinase (pERK) with IMM-1-104 compared to pretreatment baseline for patients at the third dose level (160 mg once daily oral) A median plasma half-life (t1/2) of 1.94 hours observed with IMM-1-104 across the first three dose levels evaluable (40 mg, 80 mg and 160 mg once daily oral), in patients with pancreatic and colorectal cancer with different RAS mutations, including KRAS-G12D, the most common mutation present in pancreatic cancer IMM-1-104 was well tolerated with no DLTs or SAEs observed and no drug-related adverse events beyond Grade 1 observed Based on the encouraging initial data presented today, Immuneering has updated guidance for the anticipated timing of announcing a RP2D for IMM-1-104 for its Phase 1/2a study. Management now expects to announce the RP2D in early 2024, versus prior guidance of mid-2024. Other data presented at AACR: In addition, IMM-1-104 was evaluated in humanized 3D preclinical tumor models displaying diverse mitogen‑activated protein kinase (MAPK) pathway activation events. The MAPK pathway consists of a series of protein kinases such as RAS, RAF, MEK and ERK that are involved in many important cellular processes including cell proliferation, differentiation and survival. The antitumor activity of IMM-1-104 was evaluated in 132 tumor models spanning 12 distinct tumor types in a proprietary humanized 3D tumor growth assay (3D-TGA) conducted in Immuneering’s labs in San Diego. Based on drug-response sensitivity and resistance pro a biomarker signature for IMM-1-104 was developed to project potential therapeutic response in more than 100,000 cancer patients found in the AACR Project GENIE® database. Mutational landscapes of patients within GENIE helped identify preclinical models that represent patient profiles likely to be encountered in the clinic. These results were utilized in prioritizing indications for the planned Phase 2a clinical trial. Updated Near-Term Milestone Expectations IMM-1-104 Additional trial updates expected on a periodic basis. RP2D and additional safety data expected in early 2024. IMM-6-415 IND filing expected in the fourth quarter of 2023. Conference Call Immuneering will host a conference call and live webcast at 9:00 a.m. ET / 6:00 a.m. PT on April 18, 2023, to discuss the results and provide a business update. Individuals interested in listening to the live conference call may do so by using the webcast link in the “Investors” section of the company’s website at . A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call. About IMM-1-104 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). About Immuneering Corporation      Immuneering is a clinical-stage oncology company developing 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 in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations. The company’s development pipeline also includes IMM-6-415, a universal-MAPK program, as well as several early-stage programs. For more information, please visit Forward-Looking Statements This press release includes certain disclosures that contain "forward-looking statements," including, without limitation, statements regarding Immuneering’s expectations regarding the treatment potential of IMM-1-104, the design, enrollment criteria and conduct of the Phase 1/2a clinical trial, the translation of preclinical data into human clinical data, the ability of initial clinical data to de-risk IMM-1-104 and be confirmed as the study progresses, including the safety, tolerability, pharmacokinetics, pharmacodynamics and potential efficacy of IMM-1-104; the potential advantages and effectiveness of the company’s clinical and preclinical candidates, the timing of additional trial updates, recommended phase 2 dose and additional safety data, the indications to be pursued by Immuneering in the Phase 2a portion of the study, the timing of submission of the IND for IMM-6-415, and Immuneering’s ability to advance its pipeline and further diversify its portfolio and make progress towards its longstanding goal of creating better medicines for cancer patients. Forward-looking statements are based on Immuneering’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the risks inherent in oncology drug research and development, including target discovery, target validation, lead compound identification, lead compound optimization, preclinical studies, and clinical trials. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in Immuneering’s most recent Form 10-K filed with the U.S. Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Immuneering undertakes no duty to update such information except as required under applicable law. Media Contact: Gina Nugent Nugent Communications 617-460-3579 gina@nugentcommunications.com Investor Contacts: Laurence Watts Gilmartin Group 619-916-7620 laurence@gilmartinir.com or Kiki Patel, PharmD Gilmartin Group 332-895-3225 kiki@gilmartinir.com