Mucoepidermoid Carcinoma

Partial response and stable disease reported in combination cohort, and durable stable disease observed in monotherapy cohortsNo dose limiting toxicities observed at any dose levelCleared fifth of six monotherapy cohorts and second of four combination cohortsKineta is actively exploring strategic alternatives to maximize value for all stakeholders SEATTLE, March 12, 2024 (GLOBE NEWSWIRE) -- Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, announced today an update on its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123 as monotherapy and in combination with Merck’s anti-PD therapy, KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors. KVA12123 cleared the fifth of six monotherapy dose levels and the second of four cohorts in combination with pembrolizumab. KVA12123 was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events at any dose level. Monotherapy Dose Escalation (3 – 300 mg KVA12123 Q2W) Of 21 patients enrolled, 12 received at least one baseline and one follow up scanBest overall response (BOR) in 9 of 12 patients with at least one follow-up scan is stable disease with a mean duration of 15 weeksOne patient with non-small cell lung cancer that failed 6 prior lines of therapy, including checkpoint inhibitor (CPI) therapy, has experienced stable disease lasting 28 weeksNine participants remain on-treatment Combination Therapy Dose Escalation (30-100 mg KVA12123 Q2W, 400 mg pembrolizumab Q6W) Of 9 patients enrolled, 3 received at least one baseline and one follow-up scanBOR in 2 of 3 patients with at least one follow up scan is: Stable disease in 1 CPI-failure renal cell carcinoma patient with a 24% reduction in target lesions Partial Response in 1 patient with a PD-L1 negative mucoepidermoid carcinoma and a 54% reduction in target lesions and a complete response in non-target lesions Eight patients remain on-treatment Biomarkers Dose-dependent induction of on-target pro-inflammatory cytokines and chemokinesDose-dependent increases in non-classical monocytes, CD4+ and CD8+ T cells, and NK cells Safety No DLTs observed in any patient at any dose levelNo evidence of cytokine release syndrome in any patient at any dose level “We are pleased with the progress of the study, the initial clinical response data, and the durability of patient benefit emerging from the study. We continue to be encouraged by the safety profile of KVA12123, supporting advancement to higher doses,” said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. “KVA12123 has a best-in-class potential that may offer patients a novel approach to address immunosuppression in the tumor microenvironment to better manage solid tumor cancers.” The Company recently announced its restructuring and that it is pursuing strategic alternatives to maximize shareholder value due to certain investors indicating they will not fulfill their April 2024 funding obligation in a private placement financing. As a result, the Company has suspended new patient enrollment into the Phase 1/2 VISTA-101 trial and will not be recruiting patients into either the sixth cohort in the monotherapy arm or the third cohort in the combination therapy arm. Patients currently enrolled in the trial will be permitted to continue to participate. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About KinetaKineta (Nasdaq: KA) is a clinical-stage biotechnology company with a mission to develop next-generation immunotherapies that transform patients’ lives. Kineta has leveraged its expertise in innate immunity and is focused on discovering and developing potentially differentiated immunotherapies that address the major challenges with current cancer therapy. The company’s immuno-oncology pipeline includes KVA12123, a novel VISTA blocking immunotherapy currently in a Phase 1/2 clinical trial in patients with advanced solid tumors, and a preclinical monoclonal antibody targeting CD27. For more information on Kineta, please visit www.kinetabio.com, and follow Kineta on X (Twitter) and LinkedIn. KVA12123 is a VISTA blocking immunotherapy in development as a twice weekly monoclonal antibody infusion drug being evaluated in a Phase 1/2 clinical trial for patients with advanced solid tumors. Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of cytokine release syndrome (CRS) in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 has been shown to de-risk the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer. VISTA (V-domain Ig suppressor of T cell activation) is a negative immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA induces an efficient polyfunctional immune response to address immunosuppression and drives anti-tumor responses. Cautionary Statements Regarding Forward-Looking Statements: This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The use of words such as, but not limited to, “believe,” “expect,” “estimate,” “project,” “intend,” “future,” “potential,” “continue,” “may,” “might,” “plan,” “will,” “should,” “seek,” “anticipate,” or “could” and other similar words or expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements relating to exploring strategic alternatives that may include sale of assets of the company, a sale of the company, a merger or other strategic action. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Kineta’s current beliefs, expectations and assumptions regarding the future of Kineta’s business, future plans and strategies, clinical results and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. 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Such forward-looking statements are subject to a number of material risks and uncertainties including, but not limited to: Kineta’s ability to successfully initiate and complete clinical trials; the difficulty in predicting the time and cost of development of Kineta’s product candidates; Kineta’s plans to research, develop and commercialize its current and future product candidates, including, but not limited to, KVA12123; the timing and anticipated results of Kineta’s planned pre-clinical studies and clinical trials and the risk that the results of Kineta’s pre-clinical studies and clinical trials may not be predictive of future results in connection with future studies or clinical trials; the timing of the availability of data from Kineta’s clinical trials; the timing of any planned investigational new drug application or new drug application; the risk of cessation or delay of any ongoing or planned clinical trials of Kineta or its collaborators; the clinical utility, potential benefits and market acceptance of Kineta’s product candidates; Kineta’s commercialization, marketing and manufacturing capabilities and strategy; developments and projections relating to Kineta’s competitors and its industry; the impact of government laws and regulations; the timing and outcome of Kineta’s planned interactions with regulatory authorities; Kineta’s ability to protect its intellectual property position; risks relating to volatility and uncertainty in the capital markets for biotechnology companies; availability of suitable third parties with which to conduct contemplated strategic transactions; whether Kineta will be able to pursue a strategic transaction, or whether any transaction, if pursued, will be completed on attractive terms or at all; whether Kineta’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital requirements; and those risks set forth under the caption “Risk Factors” in the company’s most recent Annual Report on Form 10-K filed with the SEC on March 31, 2023, and Quarterly Reports on Form 10-Q filed with the SEC on May 11, 2023, August 11, 2023 and November 3, 2023, as well as discussions of potential risks, uncertainties and other important factors in Kineta’s subsequent filings with the SEC. 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Researchers found that certain drugs can change the fundamental makeup of cancer stem cells in mouse models of mucoepidermoid carcinoma -- a lethal form of salivary gland cancer that currently has no treatment options. Researchers at the University of Michigan Rogel Cancer Center and School of Dentistry found that certain drugs can change the fundamental makeup of cancer stem cells in mouse models of mucoepidermoid carcinoma -- a lethal form of salivary gland cancer that currently has no treatment options. These results appeared in Clinical Cancer Research. "We observed that when we used small molecule inhibitors of MDM2 for a short period of time, the population of cancer stem cells decreased quite a bit," said Jacques Nor, D.D.S, M.S,. Ph.D., Donald Kerr Professor of Dentistry and lead author of this study. The team initially thought that the cancer stem cells were being selectively killed by this drug, but the study revealed something more profound. Cancer stem cells represent the small number of cells in a tumor that fuel cancer's growth and spread. "We found that the drug actually changes the fundamental nature of the cells to make them more vulnerable to other therapies and less able to start new tumors." Nor's team also observed that the incidence of relapse in mice treated with this drug was much lower than in the mice that were not treated. Mucoepidermoid carcinoma is the most common malignant salivary gland cancer with very limited therapeutic options. Over 3,000 people die of the disease in the United States every year, and to date there is no FDA approved drug to treat it. "There is currently no effective therapy for this cancer. Right now, these patients are typically treated with radical surgery and radiation, and that usually is insufficient. Patients die because of tumor relapse and tumor metastasis. We need a systemic drug. This is one of the first outcomes that is showing some positive signs in terms of tumor regression or inhibiting tumor relapse," Nor said. Nor has been studying for years drugs that activate P53 to see if this makes cancer cells more vulnerable to therapies. In 2019, he and his team published a study in Clinical Cancer Research that showed that small molecule inhibitors work well in mouse-models of MEC, but the team still hadn't figure out just how the drugs work. This new study moves the team one step closer to that understanding. P53 is frequently mutated in most cancers but rarely in MEC, which made these small molecule inhibitors a good candidate to study. "This drug requires a non-mutated form of P53 to work," said Nor. "In mucoepidermoid carcinoma, this drug works well because P53 is not mutated." These results show that P53 is integral to MEC and suggest that therapeutic activation of p53 could present new treatment options for patients, possibilities that energize Nor and his team. "The bottom line is we now have a drug that is in a clinical trial for patients with salivary gland cancer," he said. Additional authors: Christie Rodriguez-Ramirez, Zhaocheng Zhang, Kristy A Warner, Alexandra E Herzog, Andrea Mantesso, Zhixiong Zhang, Eusik Yoon, Shaomeng Wang, Max S Wicha Funding: National Institute of Dental and Craniofacial Research (R01-DE021139), J.E. Nor; National Institute of Dental and Craniofacial Research (R01-DE23220) J.E. Nor; National Institute of Dental and Craniofacial Research (R01-DE021139S1) C.Rodriguez-Ramirez

RP2 data demonstrates deep and durable responses in difficult to treat cancers both as monotherapy and in combination with Opdivo® (nivolumab) Initiated Phase 1 expansion of RP2 in combination with Opdivo focused on patients with liver metastases WOBURN, Mass., Nov. 12, 2021 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic™ platform, today announced updated interim data from the Phase 1 data from RP2 alone and in combination with Opdivo that continues to provide strong support for the next stage development of RP2. The poster will be presented November 12-14, 2021 at 7:00 a.m. ET to 5:00 p.m. ET at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting being held November 10-14, 2021. Updated RP2 data shows compelling durability of response as single agent and in combination with Opdivo providing additional evidence of the clinical utility of RP2 in patients with hard-to-treat, anti-PD1 failed cancers. RP2 leverages Replimune’s platform to express an anti-CTLA-4 antibody, in addition to GALV-GP R- and GM-CSF which is expressed by RP1. The Company has now fully enrolled the 30-patient cohort evaluating RP2 combined with Opdivo following previously completing enrolment of the 9-patient cohort evaluating RP2 as monotherapy. The Phase 1 clinical trial population comprised patients with advanced cancers having failed, or being ineligible for, standard of care options. The updated interim data shows: In the nine-patient monotherapy cohort with RP2, two of the initial three patients who achieved response remain in response, these being a patient with esophageal cancer (partial response; previously anti-PDL1 failed) at 22 months from entering the trial and a patient with mucoepidermoid carcinoma (complete response) at 19 months from entering the trial. As previously reported, the third responding patient with uveal melanoma with a partial response (Yervoy/Opdivo failed) progressed at 15 months from entering the trial. Updated data from the 30-patient cohort of RP2 in combination with Opdivo shows durable responses ongoing at out to >425 days. To date, seven of the 30 patient (23.3%) cohort of RP2 in combination with Opdivo have achieved partial responses, with additional patients still on study with the opportunity to achieve a response. Six of the seven responses are ongoing with depth of response having been maintained or deepened over time. The responding patients are four of nine patients with cutaneous melanoma (all anti-PD1 or anti-PD1 and anti-CTLA-4 failed), two of eight patients with uveal melanoma (anti-PD1 or anti-PD1 and anti-CTLA-4 failed) and one of three patients with squamous cell carcinoma of the head and neck (anti-PD1 failed). Biomarker data continues to demonstrate substantial increases CD8 T cells and PD-L1 expression, with T cell receptor sequencing and Nanostring expression analysis further indicating potent and broad activation of an anti-tumor immune response. No correlation has been observed between the degree of anti-tumor response and the baseline levels of PD-L1 expression, in line with the intended mechanism of action for RP2 of turning immunologically ‘cold’ tumors ‘hot’. Overall the data, including the durability of the responses, continues to support that oncolytic immunotherapy-mediated expression of anti-CTLA-4 from RP2 provides potent & systemic anti-tumor effects, without substantial additional toxicity as compared to the oncolytic backbone (RP1), including without evidence of the side effects associated with systemic ipilimumab. Based on the observation of durable clinical responses in patients with liver metastases following treatment with both RP1 and RP2, the Company has amended the clinical trial protocol to enrol an additional 24 patients with liver metastases from lung cancer, gastrointestinal cancers, breast cancer and uveal melanoma. Replimune will also be presenting three additional Trial in Progress presentations at this year’s SITC Annual Meeting Abstract Title: ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies (Trial in Progress presentation) Abstract Number: 550 Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET Location: Hall E Abstract Title: CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma (Trial in Progress presentation) Abstract Number: 547 Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET Location: Hall E Abstract Title: IGNYTE: An open-label, multicenter, phase 1/2 (Ph 1/2) clinical trial of RP1 ± nivolumab in patients with advanced solid tumors (Trial in Progress presentation) Abstract Number: 506 Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET Location: Hall E The full posters will be posted to the presentations section of the Replimune website at About Replimune Replimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 to develop the next generation of oncolytic immune-gene therapies for the treatment of cancer. Replimune is developing novel, proprietary therapeutics intended to improve the direct cancer-killing effects of selective virus replication and the potency of the immune response to the tumor antigens released. Replimune’s Immulytic® platform is designed to maximize systemic immune activation, in particular to tumor neoantigens, through robust viral-mediated immunogenic tumor cell killing and the delivery of optimal combinations of immune-activating proteins to the tumor and draining lymph nodes. The approach is expected to be highly synergistic with immune checkpoint blockade and other approaches to cancer treatment across a broad range of cancers. Replimune intends to progress these therapies rapidly through clinical development in combination with other immuno-oncology products with complementary mechanisms of action as well as in standalone indications. For more information, please visit . Forward Looking Statements This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, the potential impact of the global coronavirus pandemic and the global economy on our operations and milestones, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Investor Inquiries Chris Brinzey ICR Westwicke 339.970.2843 chris.brinzey@westwicke.com Media Inquiries Lissette Steele Verge Scientific Communications 202.930.4762 x 409 lsteele@vergescientific.com