Indolent B-Cell Non-Hodgkin Lymphoma

– Twenty patients with indolent (n=18) and aggressive (n=2) R/R B-NHL received evorpacept plus standard rituximab and lenalidomide (“R2”) – Evorpacept plus R2 was well tolerated with a safety profile similar to historical R2 – The combination achieved promising initial activity with a best overall response rate (“ORR”) of 94% and a complete response rate (“CRR”) of 83% in patients with indolent R/R B-NHL (R2 historical CRR benchmark is 34%) April 09, 2024 -- ALX Oncology Holdings Inc., (“ALX Oncology” or “the Company”) (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, today reported encouraging clinical data from the ongoing Phase 1/2 investigator-sponsored trial (“IST”) of evorpacept in combination with R2 in patients with indolent and aggressive R/R B-NHL. The new data were presented in an oral presentation at the 2024 American Association for Cancer Research (“AACR”) Annual Meeting. The clinical trial enrolled a total of 20 patients with indolent (n=18) and aggressive (n=2) R/R B-NHL where all patients had received prior rituximab and 72% had received prior chemoimmunotherapy. Patients received evorpacept 30 mg/kg Q2W (n=3) or 60 mg/kg Q4W (n=17) in combination with standard R2 treatment. The regimen was well tolerated, and there were no dose-limiting toxicities. The maximum administered dose for evorpacept was 60 mg/kg Q4W. The most common adverse events due to any cause were fatigue, ALT increase, anemia, and AST increase, all of which were mostly low grade. There were no reported treatment-related deaths on study. Patients with indolent R/R B-NHL (n=18) had a best ORR of 94% and a CRR of 83%. The median duration of response was not reached. The AUGMENT Phase 3 clinical trial1, a benchmark study in a similar patient population, reported an ORR of 78% and a CRR of 34% with R2 alone. “While standard frontline treatments have shown benefit in the indolent B-NHL setting, many patients are likely to see their disease progress after initial treatment,” said Paolo Strati, M.D., the trial’s lead investigator and Assistant Professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center. “We are pleased evorpacept in combination with R2 demonstrated a favorable safety profile and encouraging response in this patient population. These data further illustrate the importance of exploring novel combinations with evorpacept to elicit anti-tumor activity by way of the innate immune response. We are excited to build upon these preliminary results as we evaluate the evorpacept-R2 combination in the ongoing Phase 2 portion of this clinical trial in patients with previously untreated indolent B-NHL.” “These initial results reinforce evorpacept’s differentiated drug design that has resulted in anti-cancer activity while minimizing hematologic toxicities inherent to other CD47 blocking agents,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. “Furthermore, the findings presented today build upon the promising data reported from the ASPEN-01 Phase 1 clinical trial of evorpacept in combination with rituximab in R/R NHL2. We look forward to applying these and other clinical trial data to inform new evorpacept combinations in our expanding pipeline. We would like to thank the patients and research team for conducting this important clinical trial.” A Phase 1 investigator-initiated trial of evorpacept (ALX148), lenalidomide and rituximab for patients with relapsed or refractory B-cell non-Hodgkin lymphoma Session Title: Clinical Trials Minisymposium / Novel Agents and Emerging Therapeutic Strategies Presentation Date and Time: Tuesday, April 9, 2024, 2:50 PM – 3:00 PM PT Abstract: CT037 (full abstract is available online here) The presentation is available on the publications page of the ALX Oncology website here. The Phase 1/2 IST is an ongoing, open-label, single arm clinical trial designed to evaluate the safety, tolerability, and efficacy of evorpacept, otherwise known as ALX148, in combination with R2 in patients with R/R B-cell NHL (both indolent and aggressive) histology. Patient enrollment is currently open to the Phase 2 portion of the study evaluating patients with previously untreated indolent B-NHL (NCT05025800). The study is sponsored and conducted by MD Anderson Cancer Center. Approximately 500,000 people worldwide are diagnosed with NHL each year. In the U.S., NHL is the seventh most common type of cancer, and over 80,000 newly cases of NHL were estimated in 20233. NHL can be divided into two groups according to how the disease progresses: indolent and aggressive lymphomas. The most prevalent form of NHL, accounting for about 32% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma. Follicular lymphoma is the most common subtype of indolent NHL and accounts for about 17% of newly diagnosed NHL cases. Indolent B-cell lymphomas tend to grow more slowly and may have fewer signs and symptoms than aggressive lymphomas when first diagnosed. For patients with indolent B-cell lymphoma, current first-line treatments include radiotherapy, anti-CD20 monoclonal antibodies, and chemoimmunotherapy. Despite advances in treatment, follicular lymphoma remains a significant cause of death. ALX Oncology is a publicly traded, clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 immune checkpoint inhibitor and bridge the innate and adaptive immune system. ALX Oncology’s lead product candidate, evorpacept, is a next generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain. To date, evorpacept has been dosed in over 500 subjects and has demonstrated promising activity and favorable tolerability profile across a range of hematologic and solid malignancies in combination with various leading anti-cancer antibodies. ALX Oncology is currently focusing on combining evorpacept with anti-cancer antibodies, antibody-drug conjugates (“ADCs”), and PD-1/PD-L1 immune checkpoint inhibitors. Rationally engineered with an inactive Fc effector function, evorpacept’s clinical data to date has demonstrated a substantially improved safety profile over other anti-CD47 molecules in the clinic with an active Fc (i.e., binding the Fc gamma receptor on macrophages). This best-in-class safety profile allows for higher dosage with minimal overlapping toxicity in the combination treatment setting. CD47 expressed on cancer cells binds to its receptor SIRP alpha, which is predominantly expressed on two cell types: macrophages and dendritic cells. The Company’s pipeline of therapeutic candidates with standard-of-care agents include: Anti-cancer antibodies (the “don’t eat me” signal): evorpacept enables Fc-mediated antibody-dependent phagocytosis by macrophages in combination with anti-cancer antibodies (e.g., Herceptin®) with an active Fc domain, which is otherwise impaired by CD47 expression on cancer cells binding to SIRP alpha on macrophages. This same mechanism of action applies to ADCs. PD-1/PD-L1 immune checkpoint inhibitors (the “don’t activate T-cells” signal): evorpacept enables T-cell activation by dendritic cells that are constitutively inhibited by CD47 expression on cancer cells binding to SIRP alpha on dendritic cells. Activated dendritic cells present neoantigens to T-cells that once activated will kill cancer cells when the PD-1/PD-L1 inhibitory interaction is blocked by T-cell checkpoint inhibitors. References 1 Leonard J.P., et al. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. doi: 10.1200/JCO.19.00010. Epub 2019 Mar 21. PMID: 30897038; PMCID: PMC7035866. 2 Kim T., et al. ALX148, A CD47 Blocker, in Combination with Rituximab in Patients with R/R Non-Hodgkin Lymphoma. EHA Library. 06/12/2020 293736; EP1247. 3 American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. The content above comes from the network. if any infringement, please contact us to modify.

LLS TAP is a strategic funding initiative to accelerate innovative blood cancer therapeutics Strategic equity investment of €3 million to support clinical advancement of EO2463 in Non-Hodgkin’s Lymphoma PARIS, Oct. 30, 2023 (GLOBE NEWSWIRE) -- Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, today announced that it received a €3 million investment from The Leukemia & Lymphoma Society’s Therapy Acceleration Program® (LLS TAP). The funding will propel the Company’s ongoing Phase 2 SIDNEY study of EO2463 in indolent non-Hodgkin B-cell lymphoma (iNHL). “We are excited to support the clinical development of Enterome’s innovative OncoMimics™ platform to the benefit of blood cancer patients,” said Lore Gruenbaum, Ph.D., Vice President, LLS TAP. “The observed good safety pro EO2463 together with its unique mechanism of immune activation may create a substantial benefit for blood cancer patients and open the door to treatment at earlier stages of disease. Moreover, it could provide a key building block for the next generation of combination and maintenance therapies.” “We are honored to be recognized and supported by LLS’s Therapy Acceleration Program,” said Dr. Pierre Belichard, Chief Executive Officer of Enterome. “This investment represents a significant vote of confidence in our OncoMimics™-based immunotherapies. It also provides us with immediate capital and access to guidance from the most renowned scientists and experts in the field of liquid tumors, facilitating the acceleration of our ongoing Phase 2 SIDNEY study of EO2463 in iNHL. With LLS’s support, we are poised to bring this potentially transformative therapy to patients battling iNHL.” “EO2463 was designed to mimic certain proteins on B lymphocytes, activate pre-existing memory T cells, and drive anti-tumor activity against B-cell malignancies,” said Dr. Jan Fagerberg, Chief Medical Officer of Enterome. “This unique, OncoMimics™-based approach specifically targets and reduces malignant B cells in iNHL. Initial results have shown promising efficacy and tolerability in iNHL B-cell lymphomas. We look forward to our collaboration with LLS and to the continued advancement of our clinical program.” SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent non-Hodgkin lymphoma (iNHL). The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). For more information on the study, refer to Clinicaltrials.gov identifier: NCT04669171. About EO2463 EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic™ peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37 and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). About OncoMimics™ OncoMimics™ immunotherapies are designed to activate pre-existing effector memory T cells that target bacterial (non-self) peptides, which are strongly cross-reactive against selected Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid, targeted cytotoxic response against cancer. About The Leukemia & Lymphoma Society and Therapy Acceleration Program® (TAP) The Leukemia & Lymphoma Society® (LLS) is a global leader in the fight against cancer. The LLS mission is to cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Founded in 1949 and headquartered in Rye Brook, NY, LLS has regions throughout the United States and Canada. To learn more, visit . Patients should contact the Information Resource Center at (800) 955-4572, Monday through Friday, 9 a.m. to 9 p.m. ET. LLS is the only organization featured in the nonprofit category on both Fast Company’s 2022 Brands That Matter list and the 2023 Best Workplaces for Innovators list. LLS stands out among brands around the world for its relevancy, cultural impact, ingenuity, and mission impact. LLS TAP is a Mission-driven, strategic venture philanthropy initiative that seeks to accelerate the development of innovative blood cancer therapeutics and change the standard of care. LLS TAP collaborates with biotech companies to support the development of novel platforms, first-in-class assets addressing unmet medical needs, emerging patient populations and even rare blood cancers. LLS TAP accepts funding applications on a rolling basis from companies with innovative science that has a high potential to improve patient lives. To learn more, visit . Follow LLS on Facebook, Twitter, and Instagram. Contacts ENTEROME MEDIA RELATIONS Guillaume Bayre Head of External Communications Tel: +33 (0)1 76 21 58 15 communication@enterome.com LifeSci Advisors LLC Ashley R. Robinson (US) +1 617 430 7577 arr@lifesciadvisors.com Sandya von der Weid (Europe) +41 78 680 05 38 svonderweid@lifesciadvisors.com About Enterome Enterome is a clinical-stage biopharmaceutical company developing breakthrough immunomodulatory drugs for the treatment of cancer and immune diseases. Enterome’s pioneering approach to drug discovery is based on its unique and powerful bacterial Mimicry drug discovery platform, which allows it to analyze and uncover new biological insights from the millions of gut bacterial proteins in constant cross-talk with the human body. Enterome’s first-in-class small protein and peptide drug candidates modulate the immune system by closely mimicking the structure, effect or actions of specific antigens, hormones, or cytokines. The company’s two pipelines of drug candidates include: OncoMimics™ peptides, a pipeline of peptide-based immunotherapies. Lead candidate, EO2401, is in Phase 2 clinical trials in patients with glioblastoma and adrenal tumors and has demonstrated clinical proof of concept. EO2463 is in a Phase 1/2 clinical trial for indolent non-Hodgkin lymphomas, and has demonstrated a good safety pro first signs of efficacy. EO2040, a new immune therapy, is expected to start a Phase 2 trial in 2023 in patients suffering from colorectal cancer with ctDNA-defined, minimal residual disease. EO4010 is in development for third-line colorectal cancer and targeted to enter clinical trials in 2023. EndoMimics™ peptides, a pipeline of next generation bioactives acting like human hormones or cytokines, are being developed in collaboration with Nestlé Health Science, for food allergies and inflammatory bowel disease (IBD). Lead candidate, EB1010, is expected to enter the clinic in 2024. Enterome employs 70 people and is headquartered in Paris, France. Since its inception, the company has raised a total of €118 million from Europe- and U.S.-based life science investors and more than €100 million from pharmaceutical partnerships. For more information, please visit the company’s website at:

EO2463 uniquely targets four distinct B cell markers to maximize tumor killing and prevent immune escape, generating fast, strong and durable CD8+ T cell activation against malignant B cells Initial data from EONHL1-20/SIDNEY study presented at the 17th International Conference on Malignant Lymphoma (ICML) in Lugano Beneficial clinical responses observed following 6 weeks of treatment with EO2463 as monotherapy; preliminary complete response rate of 50% in evaluable patients for EO2463 in combination with lenalidomide + rituximab EO2463 is well tolerated as monotherapy, without additional safety signals when combined with lenalidomide + rituximab PARIS, France I June 14, 2023 I Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, today announces first clinical results from the Phase 1/2 (EONHL1-20/SIDNEY) trial of EO2463, an experimental treatment for indolent non-Hodgkin B cell lymphoma (iNHL). The initial data, presented at the 17 th International Conference on Malignant Lymphoma (ICML), show that EO2463, as monotherapy and in combination with the standard of care (lenalidomide and rituximab), is well tolerated and generates strong immune responses associated with early clinical activity. ICML is taking place June 13-17, 2023 in Lugano, Switzerland. EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic™ peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37 and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes that are abundant in iNHL. By ensuring broad target coverage across malignant B cells while avoiding a detrimental impact on normal peripheral B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms. Dr. Jan Fagerberg, Chief Medical Officer of Enterome said, “ EO2463 was designed to expand pre-existing memory cytotoxic T cells recognizing specific protein sequences from gut bacteria that cross-react with B cell specific proteins to drive targeted anti-tumor activity against B cell malignancies. We are very encouraged that EO2463 is showing promising efficacy with a good safety profile in indolent non-Hodgkin B cell lymphomas, confirming the validity of our approach and the ability of OncoMimics™ -based immunotherapies to target liquid tumors. We now look forward to continuing the trial with multiple expansion cohorts.” Key highlights from the EONHL1-20/SIDNEY trial poster presentation, entitled ‘ Phase 1 trial of EO2463 peptide-based immunotherapy as monotherapy and in combination with lenalidomide and rituximab in indolent non-Hodgkin lymphoma ’ : Pierre Belichard, CEO of Enterome added, “ These very promising data from the SIDNEY trial as well as the positive data from our lead OncoMimics™ candidate, EO2401, being evaluated in recurrent glioblastoma and in adrenal tumors, continue to provide strong support for the potential of Enterome’s Mimicry platform to transform cancer immunotherapy, in particular its unique ability to enable a multi-targeting approach. This growing set of clinical data gives us confidence in our ability to generate OncoMimics™-based immunotherapies targeting unmet needs across a wide range of solid and liquid tumors. Alongside EO2401 and EO2463, we have initiated enrollment for a new clinical study to evaluate EO2040 in patients with colorectal cancer with ctDNA-defined, minimal residual disease. We are also preparing to enter another new OncoMimics™ candidate, EO4010, for the treatment of metastatic colorectal cancer, into clinical development.” The abstract #435 is available here and the presentation will be available on Enterome’s website . About OncoMimics™ OncoMimics™ immunotherapies are designed to activate pre-existing effector memory T cells that target bacterial (non-self) peptides, which are strongly cross-reactive against selected Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid targeted cytotoxic response against cancer. About EO2463 EO2463 is Enterome’s second, clinical-stage off-the-shelf OncoMimics™ peptide-based immunotherapy. It combines four microbial-derived OncoMimics™ peptides that closely mimic specific cytotoxic T cell (CD8+ T cell) epitopes in B cell Tumor-Associated Antigens CD20, CD22, CD37, and CD268 (BAFF receptor), as well as a helper CD4 peptide, UCP2. The EO2463 mimic peptides are non-self, high affinity and stable MHC class I binders. About SIDNEY SIDNEY (EONHL1-20/, NCT04669171) is a multicenter, open-label, non-randomized Phase 1/2 trial investigating EO2463 in monotherapy and in combination with standard of care - rituximab and rituximab in combination with lenalidomide – for treatment of patients with indolent Non-Hodgkin's Lymphoma. The trial is assessing safety, tolerability, immunogenicity and preliminary efficacy in 60 patients at centers in the US and Europe. Patient enrollment is ongoing. About iNHL Non-Hodgkin lymphoma is the seventh most common cause of new cancer cases among both men and women, accounting for 4% to 5% of new cancer cases, and 3% to 4% of cancer-related deaths. Indolent non-Hodgkin lymphoma (iNHL) constitutes a distinct subset where, even though currently available treatments are efficacious, the main disease subtypes, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL), are considered non-curable in most patients. Thus, novel therapeutic approaches are still needed to enhance treatment outcomes and limit or delay the use of potentially more toxic therapies. About Enterome Enterome is a clinical-stage biopharmaceutical company developing breakthrough immunomodulatory drugs for the treatment of cancer and immune diseases. Enterome’s pioneering approach to drug discovery is based on its unique and powerful bacterial Mimicry drug discovery platform, allowing it to analyze and uncover new biological insights from the millions of gut bacterial proteins in constant cross-talk with the human body. Its first-in-class small protein and peptide drug candidates modulate the immune system by closely mimicking the structure, effect or actions of specific antigens, hormones, or cytokines. The company’s two pipelines of drug candidates include: Enterome employs 70 people and is headquartered in Paris, France. Since its inception, the company has raised a total of €116 million from Europe- and US-based life science investors and more than €100 million from pharmaceutical partnerships. For more information, please visit the company’s website at: www.enterome.com SOURCE: Enterome