Atezolizumab

In 33 heavily pretreated NSCLC EGFR wild-type (EGFRwt) patients the combination of AFM24 and atezolizumab shows an overall response rate (ORR) of 21% (6 confirmed responses, 1 response awaiting confirmatory scan) and a disease control rate (DCR) of 76%; tumor shrinkage was observed in 48% of patients; preliminary median progression free survival (PFS) is 5.6 months and 36% of patients remain on treatment In 17 heavily pretreated NSCLC EGFR mutant (EGFRmut) patients the combination shows an ORR of 24% and a DCR of 71%; tumor shrinkage was observed in 41% of patients; median PFS is 5.6 months and 5 patients (29%) are on treatment for over 10 months Both cohorts demonstrated a well-manageable side effect profile with no new safety signals identified A post hoc analysis demonstrated that patients who achieve higher exposure of AFM24 had significantly higher response rates and improved PFS and survival compared to patients with lower exposure Company to review results on a webcast today at 8:30 am EST / 14:30 CET Dec. 17, 2024 -- Affimed N.V. (Nasdaq: AFMD) (“Affimed,” or the “Company”), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today announced updated clinical data from the ongoing AFM24-102 trial of AFM24/atezolizumab combination therapy in heavily pretreated NSCLC patients. Results continue to demonstrate meaningful clinical activity in both NSCLC EGFRwt and EGFRmut patients with good tolerability. In addition, the Company reported findings from a post-hoc exposure-response analysis in patients treated with 480 mg AFM24 showing higher AFM24 exposure is associated with significantly better response rates, improved PFS and overall survival (OS). Based on these data, the future development program for AFM24 will use a dose of 720 mg weekly, a dose that has already been successfully tested in the phase 1 study of AFM24 showing a manageable safety profile. “With the compelling data from both EGFR wild-type and mutant cohorts, along with the exposure-response analysis we are unlocking the possibilities for the AFM24/atezolizumab combination in treating heavily pretreated NSCLC patients,” said Dr. Shawn Leland, PharmD, RPh, Chief Executive Officer of Affimed. “These findings highlight our opportunity to further refine and advance this treatment with a clear focus on patients who stand to benefit the most. We are excited about the path ahead and are committed to exploring innovative strategies to bring this promising therapy to those in need.” Patient population: As of the November 14, 2024 data cut, there were 43 patients in the full analysis set (FAS) and 33 patients in the per protocol set (PPS), defined as having one post baseline scan according to RECIST. Reasons for non-evaluability were early symptomatic deterioration (6), non-related AEs (2), too early (2). Patients had a median of 2 prior lines of therapy (range: 1–7). All patients had received platinum-based combinations and PD(L) 1 targeting checkpoint inhibitors (CPIs), and two-thirds had received taxanes. Importantly, all but one patient discontinued their previous CPI because of progression. Safety: The AFM24 and atezolizumab combination therapy was well tolerated with no unexpected safety findings. Infusion related reactions (IRRs) were the most common adverse event (AE) reported, in 54% of patients; IRRs were manageable, mostly present during the first infusion, and fully resolved. Elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), a known side effect of atezolizumab, were reported in 21% and 16% of patients respectively. Anti-tumor activity and durability (N=33, PPS): The combination demonstrated an ORR of 21% (7 responses: 1 complete response (CR), 5 partial responses (PR) and 1 additional not yet confirmed PR), tumor shrinkage in 48% of patients (16/33 patients) and a DCR of 76%. In the 7 responders, 5 had never achieved an objective response on prior CPIs and only 2 patients had a PR on previous CPI containing treatment (both to a triplet of platinum, pemetrexed and CPI). The preliminary median PFS is 5.6 months, and 36% of patients are currently on treatment. Patient population: As of the November 14, 2024 data cut, 28 patients were in the FAS (reasons for non-evaluability at the cut-off were: ongoing with no scan yet 5, early deterioration 4, non-related AEs 2), with updated results presented for the first 17 patients in the PPS. All patients had received prior EGFR specific TKI therapy, and 77% had received platinum-based chemotherapy. Anti-tumor activity and durability (N=17, PPS): AFM24 combined with atezolizumab showed promising activity in refractory NSCLC EGFRmut patients achieving an ORR of 24% (4 confirmed responses: 1 CR, 3 PRs), a DCR of 71% and tumor shrinkage in 41% of patients. With a median follow-up of 9 months, the median PFS was 5.6 months. Five (29%) patients are on treatment for over 10 months, demonstrating long term tumor control. Analysis process: A post-hoc exposure-response analysis was conducted including NSCLC EGFRwt and EGFRmut subjects (n= 44) treated with 480 mg AFM24 in both the AFM24-101 monotherapy study or the AFM24-102 AFM24 combination with atezolizumab study. Low and high exposure groups were calculated using a median cut-point of patient`s mean trough values. Safety, anti-tumor activity and durability: Baseline characteristics were balanced between the high and low exposure groups and there were no differences in body mass index or percentage of administered dose that would explain differences in exposure. The high exposure group showed an ORR of 46% and a PFS of 7.4. A sensitivity analysis using quartiles of exposure supported a clear relationship between exposure and outcome indicating that higher doses of AFM24 will likely result in improved efficacy. The PK profile of 720 mg AFM24 weekly, as tested successfully in the phase 1 trial and further pharmacokinetic modelling indicate that 720 mg will achieve exposure levels that are equal or above the plasma concentrations observed for the high exposure group. “Advanced-stage NSCLC remains one of the most challenging cancers to treat, and our findings bring new hope,” said Dr. Andreas Harstrick, MD, Chief Medical Officer of Affimed. “We see compelling efficacy results with the AFM24/atezolizumab combination in heavily pretreated NSCLC patients, independent from the mutational status. The results are remarkable as we achieve this with a purely immunotherapy-based approach in patients that are often not able or not willing to take additional toxic therapies. The insights in the relation of exposure and efficacy will allow us to further improve on the efficacy and provide a clear path forward as we strive to unlock new possibilities for EGFR NSCLC patients.” AFM24 is a tetravalent, bispecific ICE® that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK® platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The Company’s innate cell engagers (ICE®) enable a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors. ICE® are generated on the Company’s proprietary ROCK® platform which predictably generates customized molecules that leverage the power of innate immune cells to destroy tumor cells. A number of ICE® molecules are in clinical development, being studied as mono- or combination therapy. Headquartered in Mannheim, Germany, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by the bold vision to stop cancer from ever derailing patients’ lives. For more about the Company’s people, pipeline and partners, please visit: www.affimed.com. The content above comes from the network. if any infringement, please contact us to modify.

Announces preliminary Phase 1 data for XTX301, a tumor-activated IL-12, demonstrating an improved tolerability profile over historical data for rhIL-12, with no dose-limiting toxicities Completed additional private placement with Gilead for purchase of remaining equity investment in connection with XTX301 partnership WALTHAM, Mass., Dec. 19, 2024 (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 plans to present initial data from its ongoing Phase 2 trial for 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) at the ASCO Gastrointestinal (ASCO GI) Cancers Symposium in San Francisco, California from January 23-25, 2025. In addition, today the company announced preliminary data from Phase 1 dose escalation for XTX301, an investigational tumor-activated IL-12. “We are encouraged by the early evidence of responses in patients with cold tumors, including MSS colorectal cancer, reported for the combination of vilastobart and atezolizumab in Phase 1C dose escalation earlier this year, and we look forward to sharing initial Phase 2 data for the combination in MSS CRC at ASCO GI in January,” said Katarina Luptakova, M.D., chief medical officer of Xilio. “In addition, the preliminary Phase 1 data we reported today for XTX301, our tumor-activated IL-12, highlight its promising clinical profile, including no dose-limiting toxicities reported to date and consistent interferon gamma signaling observed throughout treatment cycles.” ASCO GI Presentation Details for Vilastobart (anti-CTLA-4) Xilio will present initial data from its ongoing Phase 2 trial for vilastobart (XTX101), a tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, in combination with atezolizumab (Tecentriq®) in patients with metastatic MSS CRC: Title: Phase 1/2 study of XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with advanced solid tumors and in MSS CRC Abstract Number: 206 Presentation Date: Saturday, January 25, 2025 Poster Session C: Cancers of the Colon, Rectum, and Anus Time: 7:00 AM-7:55 AM PST Location: Moscone West, San Francisco, CA In November 2024, Xilio presented encouraging initial data from the ongoing Phase 1C dose escalation trial for the combination of vilastobart and atezolizumab in patients with advanced solid tumors. For more information, read the press release here. Preliminary Data from Ongoing Phase 1 Trial for XTX301 (IL-12) As of the data cutoff date of November 25, 2024, 34 patients with advanced solid tumors had been treated with XTX301 at doses ranging from 5 µg/kg to 60 µg/kg administered once every three weeks (Q3W) or once every six weeks (Q6W). Patients were generally heavily pre-treated, and approximately 68% of patients received three or more prior lines of anti-cancer therapy. A maximum tolerated dose has not yet been established. Xilio continues to enroll patients in Phase 1A monotherapy dose escalation and Phase 1B monotherapy dose expansion of its ongoing Phase 1 clinical trial of XTX301 in patients with advanced solid tumors. In addition, preliminary results as of the data cutoff date showed: Sustained interferon gamma (IFNɣ) signaling without evidence of tachyphylaxis throughout treatment cycles. Tachyphylaxis has historically limited other IL-12 agents. Evidence of dose-dependent pharmacology with T cell, natural killer (NK) cell and NKT cell proliferation. Consistent with the tumor-activated design of XTX301, no measurable activated XTX301 was detected in peripheral circulation across all dose levels and schedules. Across all dose levels and schedules, no Grade 4 or Grade 5 treatment-related adverse events (AEs) were reported by investigators and no patients experienced a dose limiting toxicity or a dose reduction due to a treatment-related AE. In addition, across all dose levels and schedules, the majority of treatment-related AEs were Grade 1 or 2 and most commonly consisted of flu-like symptoms, cytokine release syndrome, increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased blood cell counts. Additional Private Placement with Gilead On December 18, 2024, Xilio issued and sold an aggregate of approximately $8.2 million in common stock and prefunded warrants to Gilead Sciences, Inc. (Gilead) in an additional private placement pursuant to the stock purchase agreement Xilio entered into with Gilead in March 2024. Upon the closing of the additional private placement, Xilio has issued and sold an aggregate of $25.0 million in common stock and prefunded warrants to Gilead, representing the maximum aggregate investment under the March 2024 stock purchase agreement. After giving effect to the proceeds from the additional private placement with Gilead together with Xilio’s existing cash and cash equivalents, Xilio now anticipates that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the third quarter of 2025. 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 XTX301 and the Phase 1 Clinical Trial XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic “cold” tumors towards an inflamed or “hot” state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio’s tumor-activated IL-12 program, including XTX301. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 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 to present initial data from the ongoing Phase 2 trial for vilastobart in combination with atezolizumab in patients with advanced MSS CRC; expectations regarding the clinical profile of XTX301; the period in which Xilio expects to have cash to fund its operations; and Xilio’s strategy, goals, 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; interim or preliminary preclinical or clinical data or results, 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