Grapiprant

Novel best-in-class MEK-RAF complex inhibitor IK-595 targets RAS pathway; IND in 2023 Novel paralog-selective TEAD inhibitor IK-930 advancing as planned in dose escalation; clinical data in 2023 Company prioritizes advancement of targeted oncology portfolio; cash runway extended into 2025 BOSTON, Nov. 28, 2022 (GLOBE NEWSWIRE) -- Ikena Oncology, Inc. (Nasdaq: IKNA, “Ikena”), a targeted oncology company forging new territory in patient-directed cancer treatment, today announced a next-generation mitogen-activated protein kinase (MEK)-RAF complex inhibitor, IK-595, has been nominated as the company’s first development candidate in the RAS pathway. The RAS pathway is implicated in at least half a million new cancer diagnosis each year in the United States alone. Ikena aims to target the pathway on multiple levels, including preventing known resistance mechanisms to achieve deep and sustained responses. Ikena’s new development candidate, IK-595, traps MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors. IK-595's ability to complex CRAF, in particular, prevents a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other drugs in this class. In addition, trapping CRAF in an inactive complex prevents the kinase independent anti-apoptotic function in RAS and RAF mutant cancers, a mechanism that cannot be addressed with first generation MEK inhibitors or pan-RAF inhibitors. IK-595 is being developed as an oral therapy, with a half-life enabling a pharmacokinetic profile potentially superior to other drugs, with the goal of developing an optimal therapeutic window for patients. The company plans to submit an investigational new drug application (IND) for IK-595 to the US Food & Drug Administration (FDA) in the second half of 2023. “I am thrilled to announce this addition to our pipeline, one that adds to our holistic approach to the Hippo & RAS oncosignaling network. IK-595 inhibits multiple nodes of MEK-RAF signaling, including avoiding known mechanisms of resistance,” said Mark Manfredi, PhD, Ikena’s Chief Executive Officer. “The industry’s excitement about MEK inhibition stems from its great potential as a target, but the challenges of CRAF bypass and achieving optimal target inhibition have kept first generation treatments from meeting the full potential of the target. We are hopeful that our MEK-RAF trapping approach with an optimized therapeutic window can make IK-595 a game-changing candidate for multiple indications in the RAS space.” Development Highlights, Corporate Updates, and Upcoming Milestones Advancing new development candidate, IK-595, through IND-enabling studies, targeting MEK-RAF through novel mechanisms aiming to address existing gaps in the MEK inhibitor space Preclinical differentiation data planned for presentation in the first half of 2023IND targeted in the second half of 2023 Progressing novel, paralog-selective transcriptional enhanced associate domain (TEAD) inhibitor, IK-930, in the clinic and further defining differentiation profile from panTEAD inhibition Monotherapy program progressing as planned, advanced through multiple dose escalation cohortsPreclinical data on differentiation and advantages of paralog selectivity planned for presentation in first half of 2023Initiation of osimertinib combination cohort clinical program expected in first half of 2023Initial clinical data from IK-930 monotherapy program expected in second half of 2023 Following a portfolio review, discontinuing the internal clinical development of the EP4 antagonist IK-007 and exploring strategic alternatives for this program Clinical data from IK-007 in microsatellite stable colorectal cancer (MSS-CRC) will be presented in a poster at 2022 European Society for Medical Oncology Immuno-Oncology Congress Portfolio reprioritization and streamlining of discovery and clinical activities contribute to extension of cash runway into 2025 Runway does not include any potential licensing revenue from the aryl hydrocarbon receptor (AHR) antagonist IK-175 program, currently in development in collaboration with Bristol Myers Squibb and eligible for opt-in through early 2024 “Ikena has a strong track record of internal drug discovery and development that has built our robust clinical and early-stage pipeline,” said Jotin Marango, MD, PhD, Chief Financial Officer and Head of Corporate Development of Ikena. “Our goal is to continue our leadership in targeted oncology by discovering and advancing best-in-class candidates like IK-930 and IK-595, therapies designed to address the needs of specific patient populations while at the same time building value for our shareholders.” About Ikena OncologyIkena OncologyTM is focused on developing differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance in the Hippo and RAS onco-signaling network. The Company’s lead targeted oncology program, IK-930, is a paralog-selective TEAD inhibitor addressing the Hippo signaling pathway, a known tumor suppressor pathway that also drives resistance to multiple targeted therapies. The Company’s additional research spans other targets in the Hippo pathway as well as the RAS signaling pathway, including developing IK-595, a novel MEK-RAF inhibitor. Additionally, IK-175, an AHR antagonist, is being developed in collaboration with Bristol Myers Squibb. Ikena aims to utilize their depth of institutional knowledge and breadth of tools to efficiently develop the right drug using the right modality for the right patient. To learn more, visit www.ikenaoncology.com or follow us on Twitter and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding: the timing and advancement of our targeted oncology programs, including the timing of updates; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; our ability to obtain and maintain regulatory approval of our product candidates; the implementation of our business model, and strategic plans for our business and product candidates. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of our targeted oncology programs; our expectations regarding the therapeutic benefit of our targeted oncology programs; expectations regarding our new executive officer; our ability to efficiently discover and develop product candidates; the implementation of our business model, and strategic plans for our business and product candidates, and other factors discussed in the “Risk Factors” section of Ikena’s Form 10-Q for the quarter ended September 30, 2022, which is on file with the SEC, as updated by any subsequent SEC filings. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements. Investor Contact:Rebecca CohenIkena Oncologyrcohen@ikenaoncology.com Media Contact:Gwen SchankerLifeSci Communicationsgschanker@lifescicomms.com

Ikena President and CEO Mark Manfredi, Ph.D/Courtesy Ikena Oncology Kindness. Respect. Innovation. Only one of those words typically features in biotech mission statements, but at Ikena Oncology, all three are important – and have been from day one. “We formed Ikena Oncology in 2016,” Mark Manfredi, Ph.D., president and CEO, began. “Our corporate culture was built around a lot of the things I learned throughout my time in the industry at small, medium and large companies.” Manfredi has spent more than 20 years in cancer therapeutics development and translational research. He has served as CSO at Raze Therapeutics, entrepreneur-in-residence at Atlas Ventures and VP of oncology at Takeda Pharmaceutical, where he contributed to Takeda’s global R&D strategy and helped advance eight mechanisms into the clinic. He had three goals for Ikena’s culture: 1. To create a vibrant, innovative environment for scientists. “At Millennium (acquired by Takeda in 2008), the mantra was ‘nothing is impossible.’ At Ikena Oncology, that mantra is ‘make fresh tracks,’” he said. Manfredi aims to encourage his team members to address the hard questions that have a big impact in science. “That means taking risks and working on the cutting edge. When you don’t know what’s around the corner and you may be one experiment away from possible disaster, you’re also on the edge of breakthrough discoveries. It’s exciting, but it also makes some people uncomfortable. That approach, however, has allowed us to carve out a unique program, and it makes our scientists very excited about their work.” 2. To embrace risks. Manfredi’s mandate is to develop good science that leads to good data – not merely the results the company hopes to see. This acceptance of risk, and the acknowledgment that some experiments lead in unanticipated directions, gives scientists and non-scientists alike the courage to stretch their limits. In so doing, they may achieve more than they thought possible. 3. To build a caring work environment. “Obviously, driving a R&D program into the clinic is a team sport,” he said. “Who you work with is as important as what you’re working on, so fostering a sense of caring for each other is important. This core value creates a unique environment,” and attracts impassioned people. Manfredi refers to Ikena’s nurturing professional environment as a “supporting hive.” In it, he said, “people share core values, so it’s easier for them to share their time and talent with those around them. People feel this (vibe) when they interview with us. In fact, new hires for the past 18 months have said that their number one reason for joining Ikena is our culture and our caring environment.” The corporate culture involves “everyone rowing in the same direction, and having the opportunity to interact,” Manfredi said. Now, 20 months since the first COVID-19 stay-at-home mandates, interaction is becoming easier. “We’re a hybrid office, with some people going into the office and some working remotely. When most of us (except those in the lab) were working from home, we interacted through Microsoft Teams and online functions. We had weekly ‘buzz’ meetings, where we got together and talked about our programs and corporate updates. We also instituted a social session, including games, online through Zoom.” The hour set aside for this often turned into two or more hours and helped maintain the company’s collegial culture even when everyone was apart. The ability to enhance the corporate culture despite the pandemic hints at both grit and resiliency – personal characteristics Manfredi hones as a runner. He’s run the Boston Marathon six times (his fastest time: 2 hours, 51 minutes). “There are a lot of biotech runners in Cambridge,” he said. “Running is analogous to how we think about ups and downs, and the resiliency you have to develop to succeed.” Therapeutically, Ikena develops patient-directed oncology therapies that target important signaling pathways and others that target the tumor microenvironment. They are based upon structural biology-guided chemistry and an understanding of deep cancer biology. Yet, Manfredi said Ikena’s most innovative program isn’t a program, but a mindset – specifically, the focus on the patient. “The ‘I’ in our name stands for ‘I, the patient,’ Manfredi explained. “‘Ken’ stands for the knowledge of science that the company brings to its programs.” The goal is to understand the biology of the program as it applies to a targeted patient population. “All of our programs have this patient selection approach, based on biomarkers related to the pathway,” Manfredi said. A lot of the stratification work starts early in the research stage. “In the early phases of new programs, for example, we ask what the pathway looks like in cancer patients and how much of that is activated in these patients.” Biomarkers are being applied for go/no decisions as well as for dose escalation and cohort expansion. They inform target oncology “where biomarkers are front and center to (therapeutics based upon) genetic alterations, and also to our immuno-oncology work in the tumor micro-environment, where biomarkers traditionally aren’t featured,” he said. The early use of biomarkers will, he hopes, help Ikena increase the probability of clinical benefit and avoid the failures that have beset more broad-based trials. “Next, we’re thinking about multiplexing biomarkers,” Manfredi said. This approach would use several biomarkers to address multiple areas of importance to a therapeutic, such as sensitivity to therapy, patient selection, therapeutic resistance or other factors. The company has robust clinical and research pipelines, with two programs in Phase Ib trials involving the tumor microenvironment. Its first and lead targeted oncology program just had its IND accepted. IK-930 is an oral, small molecule that inhibits the transcription factor known as TEAD in Hippo-mutated cancers. Ikena will initiate a Phase 1 clinical trial for IK-930 in early 2022. “It is looking at multiple alterations of the pathway, and also at secondary biomarkers related to therapeutic resistance,” he said. The Hippo pathway is associated with cancer pathogenesis and is genetically altered in about 10% of all cancers but in about 40% of all mesothelioma and all epithelioid hemangioendothelioma tumors. “Some of our programs that are earlier in development are looking at biomarkers that are known in the literature but that haven’t been developed as biomarkers,” he added. IK007, for example, is an oral, small molecule prostaglandin E2 receptor 4 (EP4) antagonist that has the potential to alter immunosuppression in the tumor microenvironment, resensitizing it to activity from checkpoint inhibitors. Ikena uses the higher levels of PGEM (a metabolite in the EP4 pathway) in the urine as a biomarker for this study. That Ikena is able to develop such innovative therapeutic approaches harkens back to its team. “Everything is about the team,” Manfredi said. “What I’m most proud of is the teams that I’ve built and worked with. When you have a good team that is executing and its people are passionate about what they do…their drive, their focus, are synergistic. It’s like magic.”