On November 15, 2021 ImmunoGenesis, a clinical-stage biotechnology company developing science-driven immune therapies, reported that preclinical data from its lead development programs were presented in six scientific posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (SITC 2021), which was held November 10-14, 2021, in Washington, DC. The preclinical results presented advance the development of ImmunoGenesis’ immunotherapy programs (Press release, ImmunoGenesis, NOV 15, 2021, View Source [SID1234595649]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased to have data from our programs presented at SITC (Free SITC Whitepaper)," said James Barlow, ImmunoGenesis President and CEO. "These strong study findings support our development programs focused on creating therapies that target cold cancers—including pancreatic cancers—refractory to currently available immunotherapy. We look forward to further building upon these successful results with the advancement of our drug candidates as we look to enter clinical trials next year."

Posters Related to IMGS-001: PD-L1/PD-L2 Dual-Specific Antibody with Effector Function

Human PD-L2 triggers a unique T cell inhibitory program through PD-1 engagement distinct from that of PD-L1

Using a T cell line with an NFAT reporter, this study validated that human PD-L2, unlike murine PD-L2, generates a purely co-inhibitory signal in human T cells, albeit with a reduced inhibitory potential relative to PD-L1. Further, preliminary data in a syngeneic murine model of EL4 showed that antibody dependent cellular cytotoxicity capable PD-L2 blocking antibodies are therapeutically superior to PD-L1 or PD-L2 blockade alone. The study was the first demonstration of T cell immunoregulatory functions of PD-L2, which are distinct from those of PD-L1, and demonstrate that the more tumor-selective expression pattern of PD-L2 relative to PD-L1 provides a therapeutic advantage to effector-function capable PD-L2 antibodies.

Dual-specific antibodies blocking both PD-L1 and PD-L2 engagement of PD-1 restore anti-tumor immunity

This study investigated the capacity of monoclonal antibodies capable of bivalent binding to both PD-L1 and PD-L2 to restore the function of PD-1-suppressed T cells in vitro. The study also evaluated whether enhancing the cytotoxic effector function of these bispecific antibodies might further enhance their efficacy through the depletion of tumor cells and supportive stroma. Results indicated that these bispecific antibodies restore the function of PD-1-suppressed T cells with equivalent efficiency to pembrolizumab. ADCC-capable PD-Ligand bispecific antibodies suppress the growth of U2940 lymphoma in immunodeficient mice more efficiently than Rituximab, and in a syngeneic model of PD-L1/PD-L2 double positive colon carcinoma, these antibodies demonstrate superiority to PD-1 blocking antibodies to limit tumor growth and increase survival. This study showed that ADCC-capable PD-Ligand bispecific antibodies display higher therapeutic potential than existing anti-PD-1 antibodies and represent a new class of PD-1 pathway therapeutics with significant potential for the treatment of a variety of human cancers.

Posters Related to IMGS-501: STING Immune Stimulating Antibody Conjugate (STING-ISAC)

High-potency synthetic STING agonists rewire the myeloid stroma in the tumor microenvironment to amplify immune checkpoint blockade efficacy in refractory pancreatic ductal adenocarcinoma

This study profiled myeloid-derived suppressor cell (MDSC) and M2 macrophage function following stimulation with cyclic dinucleotides (CDNs) of ascending potency using RNA sequencing and protein arrays to uncover molecular and cellular mechanisms by which stimulator of interferon genes (STING) agonists reprogram the suppressive myeloid stroma to drive proinflammatory conversion of tumor myeloid stroma to sensitize tumors to immune checkpoint blockade. For the first time, this study concluded that synthetic CDN STING agonists affect MDSC and M2 macrophage repolarization, in part through altering metabolism and c-Myc signaling. Lastly, the study demonstrated the potential for high-potency STING agonists to overcome resistance to checkpoint blockade in an aggressive orthotopic tumor model of pancreatic ductal adenocarcinoma.

Intratumoral delivery of high potency STING agonists modulates the immunosuppressive myeloid compartment and induces curative responses in checkpoint-refractory glioblastoma models

This study utilized the synthetic cyclic di-nucleotide STING agonists IACS-8803 (8803) and ML-RR-S2-CDA (MLRR) to assess survival and tumor immune infiltrate functional reprogramming in two orthotopic transplantable human and murine glioblastoma tumor models, U87 and the recently developed QPP8 (QKi-/- Pten-/- P53-/-). The study concluded that STING agonists prolong survival in human and murine orthotopic models of glioblastoma. This prolonged survival is associated with a decrease in immunosuppressive M2 functional markers in human tumor infiltrating myeloid populations. Additionally, M2-polarized microglia demonstrated a reduction in M2 functional markers and upregulation of proinflammatory M1 markers following treatment with STING agonists. Together these results indicate that delivery of STING agonists can induce proinflammatory repolarization of the glioblastoma myeloid stroma, including both infiltrating myeloid populations and brain-resident microglia, to drive prolonged survival in refractory models of glioblastoma.

Posters Related to Evofosfamide Hypoxia-Reversal Agent in Combination with Checkpoint Inhibitors

Disrupted oxygen supply and tumor hyper-oxygen consumption contribute independently to prostate cancer immune privilege

This study investigated the capacity of two mitochondrial complex I inhibitors to reduce tumor oxidative metabolism, diminish myeloid suppressive capacity, and improve anti-tumor T cell immunity, alone and in combination with evofosfamide and checkpoint blockade to sensitize unresponsive tumors to immunotherapy. This study found that while evofosfamide or inhibition of oxidative metabolism alone did not significantly impact tumor regression, dual combination and triple combination with checkpoint blockade led to a significant reduction in tumor burden. Conclusions indicate that tumor hypoxia and associated immune suppressive programming can be reduced through both local tissue remodeling and limitation of tumor oxygen metabolism. Complex I inhibition selectively inhibits tumor and myeloid cell function, while sparing T cells. This provides opportunities to craft synergistic immuno-metabolic therapies with the potential to treat cold tumor patients refractory to current FDA approved immunotherapeutics.

Hypoxia reduction in tandem with anti-angiogenic therapy remodels the PDAC microenvironment and potentiates CD40 agonist therapy

In this study, evofosfamide (TH-302, IMGS-101) and a vascular endothelial growth factor receptor-2 (VEGFR-2) blocking antibody were used to treat several syngeneic murine models, including orthotopic pancreatic cancer and a transplantable model of prostate cancer. The researchers concluded that evofosfamide and DC101 utilize unique yet complementary mechanisms to improve the survival of mice challenged with pancreatic or prostate tumors. This combination relieves hypoxic stress and simultaneously reinvigorates T cell function and reduces macrophage mediated immunosuppression. In this setting, CD40 agonist therapy provides an additive benefit in prolonging mouse survival. Put together, these data indicate that targeted reduction of hypoxia with anti-angiogenic therapy remodels the tumor microenvironment and enhances immunotherapy responses in PDAC.

About IMGS-001 PD-L1/PD-L2
ImmunoGenesis’ lead program is IMGS–001, a PD-L1/PD-L2 dual-specific inhibitor with an engineered cytotoxic effector function. As the first molecule to target PD-L2 in addition to PD-L1, IMGS-001 has the potential to shut down the entire PD-1 pathway, potentially providing superior blockade compared to other PD-1 or PD-L1 inhibitors. The built-in engineered effector function allows IMGS-001 to kill immunosuppressive cells that express PD-L1 and/or PD-L2. Preclinical data showed that IMGS–001 offered five times the response rate in cold tumors than currently available immunotherapies. Additionally, IMGS–001 can provide a foundation for add-on therapies.

About IMGS-501 STING-ISAC
STING-ISAC builds on ImmunoGenesis’ novel platform PD-L1/PD-L2 inhibitor by conjugating a STING agonist to the antibody, combining an optimal PD-1 pathway blockade with a powerful immune agonist. ImmunoGenesis is developing this agent to effectively and systemically transport the intravenously delivered STING agonist to all tumor sites and targets within the tumor microenvironment. This therapeutic advance pushes through an important barrier seen with traditional STING agonists, which consistently produce an effect only at the site of the intratumoral injection. ImmunoGenesis’ STING-ISAC, delivered intravenously, could precisely target where it is most effective across tumor sites.

About Evofosfamide
ImmunoGenesis has extended its program to include the hypoxia-reversal agent evofosfamide. Hypoxia predicts poor outcomes in patients across tumor types, as it suppresses T-cell immunity in the tumor microenvironment. Evofosfamide reduces hypoxia by a tissue-remodeling process that includes replacement of disrupted tumor vasculature with fully functional new vessels, allowing for restoration of T-cell infiltration into previously hypoxic zones. Prior Phase 1 data of evofosfamide in combination with ipilimumab resulted in an overall response rate of 17% and a disease control rate of 83% across four dose levels in 21 heavily pre-treated patients with advanced cancer. While not the primary target, this hypoxia-reversal agent sensitizes tumors for checkpoint inhibition and is on target to be in clinic in combination with immune checkpoint blockades in 2022.

On November 14, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, and NewBridge Pharmaceuticals, a specialty company in the Middle East and North Africa (MENA) regions established to bridge the access gap by partnering with global pharma and biotech companies, reported that BRUKINSA (zanubrutinib) has received approval from the Saudi Food and Drug Authority (SFDA) for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (Press release, BeiGene, NOV 14, 2021, View Source [SID1234595524]). BeiGene and NewBridge Pharmaceuticals are working together to bring BRUKINSA to healthcare providers and people living with MCL in Saudi Arabia and other MENA markets following regulatory approvals.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Non-Hodgkin’s lymphoma is a leading cause of cancer incidence and mortality in Saudi Arabia, representing a significantly unmet need for those living with diseases, such as MCL. BRUKINSA is a next-generation BTK inhibitor designed to improve tolerability issues often associated with the class and has demonstrated efficacy in clinical trials for patients with relapsed or refractory MCL," said Dr. Ahmad Absi, Hematology Section Head at the National Guard Health Affairs in Jeddah, Kingdom of Saudi Arabia.

"We are delighted that MCL patients in Saudi Arabia will now have access to BRUKINSA, a potentially best-in-class BTK inhibitor. Driven by our belief—Cancer has no borders. Neither do we, BeiGene is committed to expanding access to high-impact medicines for all patients who need them. With approval in Saudi Arabia and in the United Arab Emirates earlier this year, we are working with NewBridge Pharmaceuticals to bring BRUKINSA to more patients in the MENA region," commented Mohammed Al-Kapany, Senior Director of New Markets in MENA at BeiGene.

"The approval of BRUKINSA in Saudi Arabia represents an important milestone in our ongoing collaboration with BeiGene. With this differentiated BTK inhibitor now approved in two markets in the MENA region, we are one step closer to reaching patients living with MCL with new treatment options," remarked Joe Henein, President and CEO of NewBridge Pharmaceuticals.

The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions.

About Mantle Cell Lymphoma (MCL)

Non-Hodgkin’s lymphoma (NHL) is the third most common cancer in Saudi Arabia,1 with approximately 1,700 new cases in 2020.2 MCL is rare form of NHL, accounting for five percent of all cases. It develops in the outer edge of a lymph node called the mantle zone. Mantle cell lymphoma occurs more often in men than in women. It is usually diagnosed in people in their early 60s.3 MCL has a poor prognosis, with a median survival of three to four years, and is often diagnosed at a later stage of disease.4

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);
For the treatment of adult patients with WM (United States, August 2021);
For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*;
For the treatment of adult patients with MCL who have received at least one previous therapy (Singapore, October 2021);
For the treatment of MCL in patients who have received at least one prior therapy (Israel, October 2021);
For the treatment of adult patients with WM who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one prior therapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Russia, October 2021); and
For the treatment of adult patients with MCL who have received at least one previous therapy (Saudi Arabia, November 2021).
To date, more than 20 marketing authorization applications have been submitted for BRUKINSA for various indications.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.

BeiGene Oncology

BeiGene is committed to advancing hematology, immuno-oncology and targeted therapies in order to bring impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy subjects. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries or regions. We currently market three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, Australia and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China. BeiGene has a high quality, innovative science and medicine organization and is a leader in China with a large oncology focused commercial team.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

On November 14, 2021 InnoCare Pharma (HKEX: 09969), a commercial-stage biotech company, reported the Investigational New Drug (IND) clearance of its SHP2 (Src Homology 2 domain containing protein tyrosine phosphatase) allosteric inhibitor ICP-189 by the US Food and Drug Administration (FDA) for starting clinical trial in the United States (Press release, InnoCare Pharma, NOV 14, 2021, View Source [SID1234595528]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This open, single-arm, multicenter study aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ICP-189 as a monotherapy and combined treatment in patients with advanced solid tumors.

ICP-189 is being developed for the treatment of solid tumors as a single agent and/or in combinations with other antitumor agents.

Preclinical study shows that ICP-189 is a potent oral allosteric inhibitor of SHP2 with excellent selectivity over other phosphatases. SHP2 is a non-receptor protein tyrosine phosphatase involved in mediating MAPK signaling pathway and immune checkpoint pathway for the regulation of cellular proliferation and survival.

Dr. Jasmine Cui, Co-Founder, Chairwoman and CEO of InnoCare, said, "In less than a month after clinical approval of ICP-189 in China, our ICP-189 got clinical approval in the U.S. This is our fourth innovative drug entering clinical stage in the U.S. This year, our innovative drug candidates have been continuously recognized by the FDA: Orphan Drug Designation to pan-FGFR inhibitor gunagratinib for the treatment of cholangiocarcinoma; Breakthrough Therapy Designation to orelabrutinib for the treatment of relapsed or refractory mantle cell lymphoma; clinical approval of the second-generation pan-TRK inhibitor ICP-723… InnoCare will continue to innovate to meet the unmet clinical needs of the entire world. "

On November 14, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported the presentation of three posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington D.C. (View Source) (Press release, Antengene, NOV 14, 2021, View Source [SID1234595529]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Antengene is very pleased to present preclinical data on two of our Phase I programs, for ATG-101 and ATG-017, at the 2021 SITC (Free SITC Whitepaper) meeting on November 12, 2021. The unique mechanisms, promising preclinical safety and activity of these exciting new compounds are very much in keeping with Antengene’s mission to develop first-in-class, best-in-class medicines for cancer," said Jay Mei, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Antengene.

Dr. Mei continued, "These presentations also highlight the breadth and depth of Antengene’s drug development capabilities. The Antengene management team and I look forward to reviewing these posters, detailed below, and the Company’s exciting portfolio at our upcoming R&D Day, planned for November 16th (virtual, details below) and November 18th (in person, details below)."

Summary of Poster Presentations

Poster #893: ATG-101: Active in "Cold" tumors, No Preclinical Liver Toxicity

ATG-101 is a PD-L1 / 4-1BB bi-specific antibody that was designed to activate tumor infiltrating lymphocytes and inhibit immune checkpoints, without inducing liver toxicity. Antengene presented data from in vitro and in vivo studies that evaluated ATG-101 activity in several T-cell activation assays and multiple in vivo models, including those resistant to anti-PD(L)1 therapies.

Data in the poster showed that ATG-101 was active in anti-PD-L1 resistant and relapsed tumor models. In addition, ATG-101 increased the activation of T-cells and exhausted T-cells upon PD-L1 crosslinking (required for ATG-101 activity), rendering "cold" tumors "hot". Importantly, ATG-101 showed no liver toxicity in a GLP toxicity study (differentiating the drug vs other 4-1BB targeted monoclonals/bi-specifics) and did not induce cytokine release syndrome in an in vitro assay. ATG-101’s unique safety and efficacy properties make it a promising potential therapy for solid tumors and non-Hodgkins lymphoma.

Poster #608: Promising ATG-017 in vivo Combination Study Add to Clinical Strategy

ATG-017 is a potent small molecule kinase inhibitor targeting the extracellular signal-related kinases 1 and 2 (ERK1/2). Antengene presented data on an in vivo study that evaluated ATG-017 in combination with an anti-PD-L1 monoclonal antibody (atezolizumab), in an aggressive, immune checkpoint inhibitor resistant mouse cancer model.

Data in the poster showed that the combination enhanced the antitumor efficacy as well as increasing the percentage of infiltrating CD8+ T cells, NK cells, CD8:CD4 ratio and M1:M2 macrophage ratio in the tumor microenvironment, rendering a "cold" tumor "hot". These results demonstrated that ATG-017 has potential synergy with immune checkpoint inhibitors, providing a rationale for exploring combination therapy in the clinic in the pursuit of improved efficacy in solid tumors, including those resistant to checkpoint inhibitions.

Poster# 227: Computational Analysis Tool Enables ATG-101 Clinical Dose Selection

Bispecific antibody ATG-101 acts by forming a trimer (comprised of ATG-101 bound to PD-L1 and 4-1BB expressing cells) that activates tumor infiltrating lymphocytes and inhibits immune checkpoints. Measuring trimeric complexes is important in defining optimal clinical doses but is very challenging to do in the clinic.

Antengene and its collaborators at Applied BioMath, LLC reported on the development of a computational semi-mechanistic pharmacology model that could be used to define the clinical dose of ATG-101. It works by simulating in vivo tumor growth inhibition and predicting trimer formation, free drug levels and receptor occupancy over time. This work has enabled Antengene to define a clinically effective dose range of ATG-101 that induces >90% PD-L1 receptor occupancy, a key metric of drug activity. This valuable pharmacology tool, which may also be applied across other compounds in Antengene’s pipeline, reflects the Company’s enthusiasm to utilize novel technologies and partnerships to enhance drug development capabilities.

Details on the posters, published on the SITC (Free SITC Whitepaper) website, are shown below:

Abstract Number: 227
Title: A computational semi-mechanistic pharmacology model of ATG-101, a PD-L1/4-1BB bispecific antibody for treatment of solid tumors and NHL
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. David C. Flowers, Applied BioMath, LLC
First Author: Dr. David C. Flowers, Applied BioMath, LLC

Abstract Number: 608
Title: Synergistic effect of the combination of ATG-017, an ERK1/2 inhibitor, and immune checkpoint inhibitor in preclinical cancer models
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Peng Chen, Antengene Corporation Limited

Abstract Number: 893
Title: ATG-101, a novel PD-L1/4-1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4-1BB activation
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Hui Yuwen, Antengene Corporation Limited

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of multiple kinds of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking the binding of PD-L1/PD-1 and inducing 4-1BB stimulation. In PD-L1 over-expressed cancer cells, ATG-101 has shown potent PD-L1 crosslinking-dependent 4-1BB agonist activity, thus potentially enhancing therapeutic efficacy, whilst mitigating risk of hepatoxicity. Antengene has received U.S. FDA approval for the IND for a Phase I trial of ATG-101 in solid tumors and non-Hodgkins lymphoma and is currently conducting a Phase I study of ATG-101 in Australia for the treatment of patients with metastatic/advanced solid tumors and non-Hodgkin lymphoma.

About ATG-017

ATG-017 is a potent and selective small molecule extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. ERK1/2 are related protein-serine/threonine kinases that function as terminal kinases in the RAS-MAPK signal transduction cascade. This cascade regulates a large variety of cellular processes, including proliferation. The RAS-MAPK pathway is dysregulated in more than 30% of human cancers with the most frequent alterations being observed in RAS or BRAF genes across multiple tumor types. An ERK inhibitor enables the targeting of both RAS and BRAF mutant diseases. In nonclinical pharmacology studies, ATG-017 has demonstrated potent inhibition of ERK1/2 enzyme activity and tumor growth in vitro and in vivo. Antengene is conducting an open-label Phase I, dose-escalation study of ATG-017 in Australia for the treatment of patients with advanced solid tumors and hematologic malignancies.

About Antengene’s R&D Day

Antengene’s R&D Day will include presentations from Dr. Jay Mei, Founder, Chairman and CEO; Mr. John Chin, Chief Business Officer; Dr. Kevin Lynch, Chief Medical Officer; Dr. Bo Shan, Chief Scientific Officer, and other Company management.

The meetings will be held virtually in English on November 16, 2021, and on-site in Mandarin on November 18, 2021. A live webcast will be available on the Antengene website under "Investor Relations", on the Event Calendar page.

To attend the event, please register in advance at links below:

R&D Day English Session – Virtual Conference
Date: Tuesday, November 16, 2021
Time: 8:30 am – 11: 30 am, Eastern Time / 9:30 pm – 12: 30 am, Beijing Time
Register at: View Source
R&D Day Mandarin Session – Live Webcast of On-Site Meeting

Date: Thursday, November 18, 2021
Time: 1:30 pm – 5:30 pm, Beijing Time
Register at: View Source

On November 13, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported clinical data for lifileucel in combination with pembrolizumab in patients with advanced cancers were presented in an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Iovance Biotherapeutics, NOV 13, 2021, View Source [SID1234595521]). A slide presentation is also available on the Iovance website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Clinical data in the presentation show encouraging response rates after lifileucel plus pembrolizumab in patients with immune checkpoint inhibitor (ICI)-naïve cervical cancer, advanced melanoma, and head and neck squamous cell carcinoma (HNSCC). The clinical data also demonstrated that lifileucel can be safely combined with pembrolizumab and warrant continued investigation of tumor infiltrating lymphocyte (TIL) cell therapy combinations as early-line treatment in advanced solid tumor cancers.

David M. O’Malley, M.D., Professor, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Director of the Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC – James) and investigator in the C-145-04 study, stated, "Immune checkpoint inhibitors are standard-of-care in the treatment of several types of advanced cancer, including cervical cancer, melanoma, and head and neck cancer. Unmet needs remain to help more patients respond and to enhance the depth and durability of responses. I was impressed by the increase in overall response rate for lifileucel in combination with pembrolizumab in cervical cancer patients, which was consistent with higher response rates in head and neck cancer and melanoma patients. Taken together the clinical data show great promise for TIL in combination with pembrolizumab across multiple solid tumors."

Early-line treatment with single-agent pembrolizumab achieves an overall response rate (ORR) of 33% in patients with advanced melanoma1 and 17% in patients with HNSCC.2 Cervical cancer patients previously treated with standard-of-care systemic therapy achieve an ORR of 11%-14% with pembrolizumab monotherapy.3 Novel early-line combination therapies are needed to improve the rate and depth of responses with manageable long-term safety. Clinical data in the SITC (Free SITC Whitepaper) oral presentation included cervical cancer patients who were ICI- and chemotherapy-naïve as well as patients with ICI-naïve advanced melanoma and HNSCC. Patients across all three cohorts had high tumor burden at baseline. The ORR in all cohorts was assessed by investigator using RECIST 1.1 as follows (September 22, 2021 data cutoff):

57.1% ORR in cervical cancer (Cohort 3 in C-145-04 cervical cancer study, n=14): Eight out of 14 patients had an objective response, including one complete response (CR), six partial responses (PR), one unconfirmed PR (uPR), and five best responses of stable disease (SD). 71.4% (5/7 patients) have ongoing confirmed responses at a median study follow up of 7.6 months.
60.0% ORR in melanoma (Cohort 1A in IOV-COM-202 study, n=10): Six out of 10 patients had a confirmed objective response, including three CRs (30% CR rate) and three PRs. Three patients achieved best response of SD. One prior unconfirmed CR (uCR) and two complete metabolic responses previously reported at ASCO (Free ASCO Whitepaper) 2021 converted to confirmed CRs per RECIST 1.1 as presented at SITC (Free SITC Whitepaper) 2021. 66.7% (4/6 patients) have ongoing confirmed responses at a median study follow up of 11.5 months. These results compare to a 33% ORR (6% CR rate) for pembrolizumab monotherapy in metastatic melanoma.1 Iovance plans to expand enrollment in this cohort.
38.9% ORR in HNSCC (Cohort 2A in IOV-COM-202 study, n=18): Seven out of 18 patients had an objective response, including one CR, one uCR, four PRs, one uPR, and seven best responses of SD. 50.0% (3/6 patients) have ongoing confirmed responses at a median study follow up of 7.8 months.
Safety: The treatment-emergent adverse event (TEAE) profile across all three cohorts was consistent with the underlying disease and known adverse event (AE) profiles of pembrolizumab, nonmyeloablative lymphodepletion (NMA-LD), and IL-2.
Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "The encouraging results for Iovance TIL plus pembrolizumab across several tumor types validate the combination of checkpoint inhibition and TIL cell therapy as a potential platform approach in solid tumors. We observed response rates that are approximately double compared to what was seen with single-agent pembrolizumab in early-line melanoma and head and neck cancers as well as second-line cervical cancer. We are eager to continue our investigation of TIL combinations in melanoma, head and neck, cervical and non-small cell lung cancer patients in need of treatment options that provide higher response rates, and deeper responses with more complete responses."

Iovance Posters and Presentations at SITC (Free SITC Whitepaper) Annual Meeting (November 12-14, 2021)

Title: Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers
Authors: D O’Malley, et al.
Presentation Type: Oral Presentation
Date and Time: Saturday, November 13, 2021 at 4:30 p.m. ET
Abstract ID: 492

Title: First phase 2 results of autologous tumor-infiltrating lymphocyte (TIL; LN-145) monotherapy in patients with advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer (NSCLC)
Authors: A Schoenfeld, et al.
Presentation Type: Poster
Abstract ID: 458

Title: Successful generation of tumor-infiltrating lymphocyte (TIL) product from renal cell carcinoma (RCC) tumors for adoptive cell therapy
Authors: B Halbert, et al.
Presentation Type: Poster
Abstract ID: 176

Title: Expansion of tumor-infiltrating lymphocytes (TIL) using static bag for the clinical manufacturing rapid expansion protocol (REP) process
Authors: K Onimus, et al.
Presentation Type: Poster
Abstract ID: 101

Conference Call and Webcast on Saturday, November 13, 2021 at 5:30 p.m. ET
Iovance will host a webcast and conference call on Saturday, November 13, at 5:30 p.m. ET to discuss SITC (Free SITC Whitepaper) clinical data updates for Iovance TIL in advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer as well as Iovance TIL in combination with pembrolizumab in patients with advanced cancers.

Iovance senior leadership will be joined by the following key opinion leaders and principal investigators in Iovance clinical studies:

Omid Hamid, M.D., Chief of Research/ImmunoOncology, The Angeles Clinic and Research Institute; Co-Director, Cutaneous Malignancy Program, Cedars Sinai CANCER
David M. O’Malley, M.D., Professor of Obstetrics and Gynecology at The Ohio State University College of Medicine; Director of the Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)
Adam J. Schoenfeld, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center
The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 3263399. The live webcast can be accessed in the Investors section of the company’s website at www.iovance.com. The archived webcast will be available for one year following the event.