Atezolizumab

27% preliminary response rate observed in heavily pre-treated microsatellite stable colorectal cancer (MSS CRC) patients without liver metastases Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) and improvement in clinical symptoms Data continue to demonstrate differentiated safety and tolerability profile for the combination with low incidence of immune-related adverse events Xilio Therapeutics to host investor conference call and webcast on Wednesday, January 22, 2025, at 8:30 am ET WALTHAM, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced initial data from its ongoing Phase 2 clinical trial evaluating vilastobart (XTX101), a tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, in combination with atezolizumab (Tecentriq®) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC). The data will be presented in a poster session (abstract #206) at the American Society of Clinical Oncology 2025 Gastrointestinal Cancer Symposium (ASCO GI) being held January 23-25, 2025, in San Francisco. “We are very encouraged by the initial Phase 2 proof-of-concept data for the combination of vilastobart and atezolizumab in heavily pre-treated patients with MSS colorectal cancer, including partial responses accompanied by marked decreases in tumor biomarkers and improvement in clinical symptoms,” said Katarina Luptakova, M.D., chief medical officer of Xilio. “We believe these data highlight the important contribution of vilastobart in this combination, as PD-(L)1 inhibitors alone have demonstrated no meaningful efficacy in patients with MSS CRC to date. The preliminary evidence of anti-tumor activity, together with continued evidence of a well-tolerated safety profile, support the potential for the combination in MSS colorectal cancer, as well as in other tumors that have traditionally been resistant to treatment with immunotherapy. We look forward to sharing additional Phase 2 data, including further follow-up, in patients with metastatic MSS CRC in the middle of this year.” “These preliminary Phase 2 data for the combination of vilastobart and atezolizumab show clear responses for patients with MSS colorectal cancer, an area of very high and increasing unmet medical need,” said J. Randolph Hecht, M.D., Professor of Clinical Medicine at the David Geffen School of Medicine at UCLA, Director of the UCLA Gastrointestinal Oncology Program and the lead author for the presentation at ASCO GI. “I am excited to see these initial data highlighting the potential for vilastobart, a tumor-activated anti-CTLA-4, in combination with PD-(L)1 inhibitors to have clinically meaningful benefit in a classically immunotherapy-resistant major malignancy.” Data from Phase 2 Trial for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic MSS CRC As of a data cutoff date of January 13, 2025, 40 patients with metastatic MSS CRC had been treated with the combination of vilastobart at a dose of 100 mg once every six weeks (Q6W) and atezolizumab at 1200 mg once every three weeks (Q3W). The median age was 55 years (ranging from 25 to 82 years), and patients were heavily pre-treated, with 70% of patients having previously received three or more prior lines of anti-cancer therapy. Preliminary Anti-Tumor Activity Data In patients without liver metastases, the preliminary objective response rate (ORR) was 27% with three partial responses (PRs), including two confirmed PRs. Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) as well as improvement in clinical symptoms. As of the data cutoff date, 18 patients had at least one imaging scan reported and were evaluable for response assessment (per RECIST version 1.1 criteria), including 11 patients without liver metastases and seven patients with liver metastases. In response-evaluable MSS CRC patients without liver metastases, investigators reported three PRs (two confirmed, one pending confirmation), with each patient ongoing on treatment as of the data cutoff date: PR (confirmed) with a 47% decrease in the sum of diameters of target lesions at 13 weeks accompanied by a decrease in levels of the serum tumor marker CEA, a multi-log fold decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. CEA is a serum biomarker that is often elevated in many malignancies, including colorectal cancer, and ctDNA is a biomarker found in the bloodstream of patients with cancer. PR (confirmed) that continued to deepen over time with a 57% reduction in the sum of diameters of target lesions at 18 weeks accompanied by a multi-log fold decrease in ctDNA to undetectable levels and significant decrease in levels of the serum tumor marker CEA to normal values. PR (pending confirmation) with a 35% decrease in the sum of diameters of target lesions at nine weeks accompanied by a decrease in levels of the tumor marker CEA to normal values, a substantial decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. For this patient, the initial response on CT imaging was assessed by the investigator and the radiology assessment is pending. In addition, an MSS CRC patient without liver metastases but with a peritoneal metastasis had a 24% decrease in the sum of diameters of target lesions assessed by CT imaging at their initial nine-week scan accompanied by a decrease in levels of the serum tumor marker CEA to normal values. This patient was ongoing on treatment as of the data cutoff date. Investigators reported stable disease in three patients without liver metastases and one patient with liver metastases, representing a preliminary disease control rate of 55% and 14%, respectively, and highlighting additional evidence of anti-tumor activity for the combination. As of the data cutoff date, 23 patients were ongoing on treatment, including 13 patients who had not yet had a first response assessment. Preliminary Safety Data Safety data continue to support the potential for vilastobart to be a differentiated next-generation anti-CTLA-4 in combination with PD-(L)1 inhibitors. Consistent with the tumor-selective design for vilastobart, the combination was generally well-tolerated, with patients experiencing a low incidence of immune-related adverse events (irAEs) and only 5% of patients reporting colitis. As of the data cutoff date, 40 patients were evaluable for safety. Across all patients treated: Investigators reported only six patients with Grade 3 or 4 treatment-related adverse events (AEs), including only two Grade 4 treatment-related AEs (laboratory abnormalities of thrombocytopenia and neutropenia, one patient each), and no Grade 5 treatment-related AEs. No patients experienced a dose reduction for vilastobart due to an AE, and only three patients discontinued treatment for the combination of vilastobart and atezolizumab due to a treatment-related AE. Investigators reported minimal endocrine irAEs (5%) and limited skin irAEs (13%), and the incidence of endocrine and skin irAEs was consistent with the incidence reported for atezolizumab alone. The most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were the following: fatigue (30%); diarrhea (20%); infusion-related reactions (13%, with 8% deemed related to vilastobart and 5% deemed related to atezolizumab); pyrexia (10%); aspartate aminotransferase (AST) increase (10%); and alanine aminotransferase (ALT) increase (10%). The only Grade 3 treatment-related AE with ≥5% incidence reported by investigators was colitis (5%). Non-laboratory Grade 3 treatment-related AEs (<5% incidence) consisted of the following: maculopapular rash and febrile neutropenia in one patient; lower gastrointestinal hemorrhage in one patient with thrombocytopenia; and one patient with Triple M overlap syndrome (myocarditis, myositis and myasthenia gravis). Clinical Development Plans for Vilastobart The Phase 2 clinical trial evaluating vilastobart in combination with atezolizumab in patients with MSS CRC is currently ongoing, and Xilio expects to report updated data from the Phase 2 trial in the middle of 2025, including additional response assessments and follow-up. These initial Phase 2 proof-of-concept data demonstrate the potential for vilastobart as a combination therapy in patients with MSS CRC and a range of other tumor types, including “cold” tumors historically resistant to immunotherapy. Based on these data, Xilio plans to seek opportunities for partnering to prioritize and expand further development beyond the initial Phase 2 proof-of-concept trial in MSS CRC. In addition, Xilio continues to enroll patients in Phase 1C dose escalation and evaluate the combination of vilastobart at the 150 mg Q6W dose level and atezolizumab at 1200 mg Q3W. Investor Conference Call Information Xilio will host a conference call and webcast tomorrow (Wednesday, January 22, 2025) at 8:30 am ET to discuss the initial Phase 2 data for the combination of vilastobart and atezolizumab. Viewers can access the webcast by using this link. Listeners who require dial-in access should register here to receive a unique PIN and information to join the call. Listeners are encouraged to join at least 15 minutes prior to the scheduled start time. The webcast will also be accessible under “Events & Presentations” in the Investors & Media section of the Xilio Therapeutics website at https://ir.xiliotx.com. A replay of the webcast will be archived on the website for 30 days following the presentation. About Vilastobart (XTX101) and the Phase 1/2 Combination Clinical Trial Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq®) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the safety and efficacy of the combination in Phase 2 in patients with metastatic microsatellite stable colorectal cancer with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details. About Xilio Therapeutics Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary platform to advance a pipeline of novel, tumor-activated clinical and preclinical I-O molecules that are designed to optimize the therapeutic index by localizing anti-tumor activity within the tumor microenvironment, including tumor-activated cytokines, antibodies, bispecifics and immune cell engagers. Learn more by visiting www.xiliotx.com and follow us on LinkedIn (Xilio Therapeutics, Inc.). Cautionary Note Regarding Forward-Looking Statements This 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 plans, expectations and anticipated milestones for vilastobart (XTX101), including plans and timing for reporting Phase 2 clinical data for vilastobart in combination with atezolizumab in patients with MSS CRC; the potential benefits of vilastobart (as a monotherapy or combination therapy with a PD-(L)1 or other agent) or any of Xilio’s other current or future product candidates in treating patients as a monotherapy or combination therapy in any indication; the ultimate safety profile of vilastobart; and Xilio’s strategy, goals and anticipated financial performance, milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “seek,” “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 important risks, uncertainties and other 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, general market conditions; risks and uncertainties related to ongoing and planned research and development activities, including initiating, conducting or completing preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned preclinical studies or clinical trials or the development of Xilio’s current or future product candidates; Xilio’s ability to obtain and maintain sufficient preclinical and clinical supply of current or future product candidates; Xilio’s advancement of multiple early-stage immune cell engager programs, including tumor-activated immune cell engagers and tumor-activated effector-enhanced immune cell engagers; initial, preliminary or interim preclinical or clinical data or results (including without limitation, the Phase 2 data for vilastobart and the preliminary investigator-reported PR awaiting radiology confirmation), which may not be replicated in or predictive of future preclinical or clinical data or results; Xilio’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; results from preclinical studies or clinical trials for Xilio’s product candidates, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of current or future clinical trials; Xilio’s ability to obtain, maintain and enforce patent and other intellectual property protection for current or future product candidates; Xilio’s ability to obtain and maintain sufficient cash resources to fund its operations; the impact of international trade policies on Xilio’s business, including U.S. and China trade policies; Xilio’s ability to maintain its clinical trial collaboration with Roche to develop vilastobart in combination with atezolizumab; and Xilio’s ability to maintain its license agreement with Gilead to develop and commercialize XTX301. These and other risks and uncertainties are described in greater detail in the sections entitled “Risk Factor Summary” and “Risk Factors” in Xilio’s filings with the U.S. Securities and Exchange Commission (SEC), including Xilio’s most recent Quarterly Report on Form 10-Q and any other filings that Xilio has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Xilio’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Xilio explicitly disclaims any obligation to update any forward-looking statements. This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release. TECENTRIQ is a registered trademark of Genentech USA, Inc., a member of the Roche Group. Investor and Media Contact Scott Young Vice President, Investor Relations and Corporate Communications investors@xiliotx.com

SON-1010, after receipt of data suggesting clinical benefit when administered as a monotherapy in patients with advanced solid tumors, enters combination evaluation with trabectedin (Yondelis®) with the potential to improve trabectedin’s therapeutic window in soft-tissue sarcoma patients Combined mechanisms have the potential to enhance progression-free survival (PFS) in some of the largest cohorts of patients with soft-tissue sarcoma Topline safety data of the combination of SON-1010 with trabectedin is expected in H2 calendar year 2025 Sonnet management discusses what this expansion means in a Virtual Investor “What This Means” segment; Access here PRINCETON, NJ, Jan. 21, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, announced today an expansion of its Phase 1 SB101 clinical study of SON-1010 (IL12-FHAB) in adult patients with advanced solid tumors to add a new cohort to evaluate the effect of SON-1010 in combination with trabectedin (Yondelis®), following the successful completion of monotherapy dose escalation. This expansion will explore the immune-oncology impact of SON-1010 at the maximum tolerated (MTD) dose of 1200 ng/kg in combination with trabectedin, which is an approved chemotherapeutic drug for certain advanced soft-tissue sarcomas (STS). Patients with STS could potentially benefit from an enhanced local immune response in the tumor microenvironment (TME). Enrollment in this cohort is underway and is expected to be completed in H1 calendar year 2025. Topline safety data of the combination with trabectedin is expected in H2 calendar year 2025; no new safety concerns have been reported to date. Additionally, the Company announced the release of a “What This Means” segment to discuss the expansion of the Phase 1 clinical study which is now available here. “The Sarcoma Oncology Center is pleased to have been able to enroll most of the patients in Sonnet’s Phase1 SB101 study to date, with the majority of the patients having STS,” commented Dr. Sant Chawla, Principal Investigator at the Sarcoma Oncology Center in Santa Monica, California. “Additionally, as we have contributed to the development of trabectedin over the years, we were excited to see its approval in early 2024 as a monotherapy in the second-line treatment for two of the most common types of sarcoma — liposarcoma and leiomyosarcoma. While the trabectedin approval was based on several clinical trials in sarcoma, we believe a large unmet need remains for the treatment of STS. We believe that combining trabectedin with SON-1010 has the potential for a natural synergistic effect of the two mechanisms of action.” The Company expects to enroll up to 18 patients with unresectable, metastatic liposarcoma or leiomyosarcoma in this open-label, single-arm expansion cohort. The patients will be treated with SON-1010 in combination with the standard 21-day trabectedin cycles, alternating the dosing of the two drugs. This number of subjects may be needed to see a statistical benefit in the response using the standard RECIST paradigm. The primary outcome measures for the Phase 1 SB101 trial are the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SON-1010 and to establish the MTD, which has been set at 1200 ng/kg. The Company believes the results of this expansion cohort could position SON-1010 for a larger Phase 2 study that could establish the combination of SON-1010 and trabectedin as a new and potentially improved treatment for STS. “The ability to assess earlier-stage patients is an exciting opportunity to evaluate the potential for SON-1010 to turn ‘cold’ tumors ‘hot’,” said Richard Kenney, M.D., Sonnet's Chief Medical Officer. “Most Phase 1 studies in the oncology space are done in patients with advanced disease, whose immune systems may not respond optimally after multiple types of chemotherapy. Trabectedin’s approval as a single agent second-line therapy in STS provides access to patients at an earlier stage with an underlying immune response that may be more robust.” “The Sonnet team has been studying the efficacy and safety of SON-1010 as a single agent, which has thus far suggested clinical benefit when administered as a monotherapy in patients with advanced solid tumors,” said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. “Further, we believe this synergy could improve the response in a serious type of cancer at an earlier stage of disease, which could open up another potential opportunity for partnering.” SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using genetic fusion to Sonnet's Fully Human Albumin Binding (FHAB®) platform, which extends the half-life and bioactivity of the IL-12 component due to binding native albumin in the serum. Albumin naturally targets the TME by strong binding to gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC). The majority of patients enrolled to date in the Phase 1 SB101 trial have STS, which has a known potential for an enhanced response to immunotherapy. Trabectedin is an alkylating DNA-binding agent that was approved as a second-line treatment in early 2024 for patients with unresectable, metastatic liposarcoma or leiomyosarcoma who have received a prior anthracycline-containing regimen. It is also known to activate tumor macrophages into a pro-inflammatory phenotype. The Company believes that SON-1010 has the potential to complement that activity by activating the NK and T cells in the TME to secrete more interferon-gamma (IFNγ) which is considered to be important for anti-tumor control. For more information about the Phase 1 SB101 trial in adult patients with advanced solid tumors visit www.clinicaltrials.gov and reference identifier NCT05352750. SON-1010 is also being evaluated in a Phase 1b/2a dose-escalation and proof-of-concept study (SB221) in combination with SON-1010 and atezolizumab (Tecentriq®) (in collaboration with Genentech, a member of the Roche Group), which is focused on platinum-resistant ovarian cancer (PROC) (NCT05756907). Enrollment remains ongoing and an update on safety at the MTD in that trial is expected in Q1 calendar year 2025. About SON-1010 SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This single-chain antibody fragment was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer, such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant to this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold' tumors ‘hot' by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells. About the Phase 1 SB101 Trial This first-in-human study is primarily designed to evaluate the safety of multiple ascending doses of SON-1010 in cancer patients and is being conducted at several sites across the United States. While the optimal dose is unknown at this stage, the potential to target the tumors, the extended PK mechanism, and our preclinical data suggest the therapeutic dose may be lower compared to native human IL-12. The study, utilizing a standard 3+3 oncology design in at least five cohorts, established the MTD at 1200 ng/kg using subcutaneous injections of SON-1010 every 3 to 4 weeks. The primary endpoint explores the safety and tolerability of SON-1010, with key secondary endpoints intended to measure PK, PD, immunogenicity, and anti-tumor activity. This study will form the basis for potential combinations with other types of immunotherapies and the future development of bispecific candidates using the FHAB platform. About Sonnet BioTherapeutics Holdings, Inc. Sonnet is an oncology-focused biotechnology company with a proprietary platform for developing targeted biologic drugs with single or bifunctional action. Known as FHAB (Fully Human Albumin-Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's FHAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. FHAB platform is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies and vaccines. Sonnet’s lead program, SON-1010, or IL-12-FHAB, is in development for the treatment of solid tumors and ovarian cancer. SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement, along with ancillary Quality and Safety Agreements, with Roche in combination with atezolizumab (Tecentriq®) for the treatment of platinum-resistant ovarian cancer (PROC). The Company is also evaluating its second program, SON-1210, an IL12-FHAB-IL15 for solid tumors, in collaboration with the Sarcoma Oncology Center to commence an investigator-initiated and funded Phase 1/2a study for the treatment of pancreatic cancer. The Company’s SON-080 program is a low dose of rhIL-6 in development for Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Diabetic Peripheral Neuropathy (DPN). SON-080 demonstrated encouraging results in a Phase 1b/2a clinical trial, being well tolerated with no evidence of a pro-inflammatory cytokine response. In October 2024, Sonnet announced an India license agreement with Alkem Laboratories, Inc. who will assume responsibility for advancing development of the SON-080 program into a Phase 2 study in DPN. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the outcome of the Company’s clinical trials, the Company's cash runway, the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investor Relations Contact: JTC Team, LLC Jenene Thomas 908-824-0775 SONN@jtcir.com Released January 21, 2025