On May 29, 2020 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported details of its AFM13 REDIRECT clinical trial design and rationale at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Annual Meeting, being held in virtual format on May 29-31, 2020 (Press release, Affimed, MAY 29, 2020, View Source [SID1234558707]).

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AFM13 is a first-in-class innate cell engager that induces specific and selective killing of CD30-positive tumor cells by engaging and activating NK cells and macrophages thereby leveraging the power of the innate immune system. As detailed in the poster at ASCO (Free ASCO Whitepaper), REDIRECT is a registration-directed trial with AFM13 as monotherapy in patients with relapsed/refractory peripheral T cell lymphoma or transformed mycosis fungoides. The study is actively recruiting.

"We recognize that we target difficult to treat malignancies and we are committed to advancing AFM13 in the clinic for patients who currently have limited treatment options," said Dr. Andreas Harstrick, Affimed’s Chief Medical Officer. "Having received the U.S. FDA orphan drug designation for AFM13 last month further reinforced our commitment to this area with high unmet medical need and the importance of developing new therapies."

The REDIRECT poster presented at ASCO (Free ASCO Whitepaper) is available online at View Source

About AFM13

AFM13 is a first-in-class tetravalent, bispecific innate cell engager that specifically binds to CD30 on tumor cells and to CD16A on NK cells and macrophages. AFM13 is being developed in peripheral T cell lymphoma (pTCL) and in other CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy as a monotherapy in CD30-positive non-Hodgkin lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD-1 antibody Keytruda (pembrolizumab) in Hodgkin lymphoma (HL) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition. AFM13 has been granted orphan drug designation by the U.S. Food and Drug Administration for HL.

On May 29, 2020 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for IO-202, an antibody targeting an immune inhibitory receptor LILRB4 (Press release, Immune-Onc Therapeutics, MAY 29, 2020, View Source [SID1234558724]). IO-202 is the first T-cell activator for acute myeloid leukemia (AML). In preclinical studies, IO-202 has shown evidence of activating T cell cytotoxicity against leukemia cells and blocking tumor infiltration. Immune-Onc’s first Phase 1 trial with IO-202 will evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity in AML patients with monocytic differentiation and in chronic myelomonocytic leukemia (CMML) patients.

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"The FDA clearance to proceed with the first-in-human trial of IO-202 in AML and CMML is an important milestone for our company," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "Acute myeloid leukemia is a devastating disease that needs new approaches and better treatment options. We look forward to working with investigators as we advance the first anti-LILRB4 antibody into the clinic."

The Phase 1 trial will begin with a dose-escalation phase to identify the optimal dose of IO-202. Once the recommended dose of IO-202 is selected, the trial will enroll patients in an expansion cohort to evaluate IO-202 as monotherapy. There is potential to evaluate IO-202 in combination with other agents with a protocol amendment. Biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials.

ABOUT AML and CMML

AML, the most common acute leukemia (blood and bone marrow cancer) in adults, is characterized by the proliferation of abnormal myeloblasts (a type of white blood cell) in the bone marrow. Nearly 20,000 new cases are expected in the U.S. in 2020. Despite advances in treatment, less than 30 percent of acute myeloid leukemia patients are alive five years after initial diagnosis.

CMML is a cancer that starts in blood-forming cells in the bone marrow and invades the blood. The condition is rare, with about 1,100 cases in the U.S. each year.

ABOUT IO-202

IO-202 is a first-in-class monoclonal antibody that blocks signaling of leukocyte immunoglobulin-like receptor B4 (LILRB4), an immune inhibitory receptor, with high binding affinity and specificity. In October 2018, Immune-Onc and The University of Texas announced the publication of pioneering research in Nature (DOI: 10.1038/s41586-018-0615-z) illuminating the roles of LILRB4 in immune suppression and tumor infiltration in AML. IO-202 is the first T-cell activator for AML. Preclinical studies showed that IO-202 can convert a "don’t kill me" to "kill me" signal by activating T cell killing of AML cells and a "don’t find me" to "find me" signal by inhibiting leukemia infiltration. IO-202 will be evaluated in AML and CMML in a Phase 1 trial, and Immune-Onc plans to explore its potential in other hematologic malignancies and solid tumors in future trials.

On May 29, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that new and updated analyses on the ongoing studies of savolitinib and surufatinib at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, May 29-31, 2020 (Press release, Hutchison China MediTech, MAY 29, 2020, https://www.chi-med.com/chi-med-to-discuss-select-global-clinical-trial-data-presented-at-asco20/ [SID1234558740]). Chi-Med will hold a conference call and audio webcast on Monday, June 1, 2020, at 1 p.m. GMT / 8 a.m. EDT / 8 p.m. HKT to review select clinical data and discuss development plan next steps.

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A live audio webcast of the call will be broadcast via Chi-Med’s website at www.chi-med.com/event. Investors may participate in the call using one of the following dial-in numbers: 1‑866‑213‑0992 (U.S. toll-free) / 0800‑032‑2849 (U.K. toll-free) / +852-2112-1888 (Hong Kong). Additional dial-in numbers are also available at Chi-Med’s website. Please use participant access code "6929001#."

Savolitinib, a potent, highly selective oral inhibitor of mesenchymal epithelial transition receptor ("MET")

In clinical studies to date, involving over 1,000 patients, savolitinib has shown promising clinical efficacy in patients with MET gene alterations in multiple tumor types with an acceptable safety profile.

Presentation Title: Phase II study of savolitinib in patients with pulmonary sarcomatoid carcinoma ("PSC") and other types of non-small cell lung cancer ("NSCLC") harboring MET exon 14 skipping
Authors: S Lu, J Fang, X Li, L Cao, J Zhou, Q Guo, Z Liang, Y Cheng, L Jiang, N Yang, Z Han, J Shi, Y Chen, H Xu, H Zhang, D Zhang, J Li, L Wang, Y Ren, W Su
Abstract Link: 9519
This is an ongoing China Phase II study of savolitinib monotherapy in NSCLC patients with MET exon 14 skipping mutations who have failed prior systemic therapy or are unable to receive chemotherapy (clinicaltrials.gov number NCT02897479), in which savolitinib demonstrated promising anti-tumor activity and acceptable tolerability. Approximately 35% of patients in the study have an aggressive subtype of NSCLC, PSC).[i] Treatment naïve patients accounted for approximately 40% of the treated patients while the remainder received prior treatments.

As of March 31, 2020, confirmed responses were seen in 49.2% of efficacy evaluable patients and disease control were seen in 93.4% of efficacy evaluable patients.

Data were not mature for Duration of Response ("DoR"), Progression Free Survival ("PFS") and Overall Survival ("OS"). Median DoR was 9.6 months (95% confidence interval ["CI"] 5.5–not reached ["NR"]) with maturity of 40%. Median PFS was 6.9 months (95% CI 4.2–19.3) with maturity of 50%. Median OS was 14.0 months (95% CI: 9.7–NR) with maturity of 46%. Efficacy observations were consistent across subgroups in this analysis.

Clinical data indicate an acceptable safety profile of savolitinib in patients with locally advanced or metastatic NSCLC who had MET exon 14 skipping mutations, with a low rate of adverse event ("AE") related discontinuations of 14.3%.

On May 29, 2020, a new drug application ("NDA") for savolitinib in this setting was accepted for review by the China National Medical Products Administration.

Presentation Title: SAVOIR: A phase III study of savolitinib versus sunitinib in patients with MET-driven papillary renal cell carcinoma ("PRCC")
Authors: TK Choueiri, DYC Heng, JL Lee, M Cancel, RB Verheijen, A Mellemgaard, L Ottesen, MM Frigault, A L’Hernault, Z Szijgyarto, S Signoretti, L Albiges
Abstract Link: 5002
In this global study of savolitinib monotherapy compared with sunitinib in patients with MET-driven, locally advanced or metastatic PRCC, savolitinib demonstrated encouraging efficacy and an improved safety profile versus sunitinib (NCT03091192). This Phase III study was stopped in late 2018 due to confounding results from a separate, external, retrospective observational study. 60 randomized patients (33 savolitinib, 27 sunitinib) were followed through August 19, 2019. Although patient numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy versus sunitinib, with fewer grade ≥3 AEs and fewer dose modifications. Based on these data, AstraZeneca and Chi-Med are actively evaluating the opportunity to restart clinical work in PRCC for monotherapy savolitinib.

Savolitinib patients had not reached median OS at data cut-off, compared to 13.2 months for sunitinib patients (hazard ratio ["HR"] 0.51; 95% CI: 0.21–1.17; p=0.110). Median PFS was 7.0 months for savolitinib patients, compared to 5.6 for sunitinib patients (HR 0.71; 95% CI 0.37–1.36; p=0.313).

Responses were observed in 27% and 7% of savolitinib and sunitinib patients, respectively. This difference did not reach statistical significance due to the small sample size. None of the 9 responders on savolitinib treatment experienced disease progression as of data cut-off, compared to 1 of 2 responders on sunitinib treatment. Sunitinib response rate was in range with previous studies.[ii],[iii]

Grade ≥3 AEs were reported in 42% of savolitinib patients versus 81% of sunitinib patients, with AEs leading to dose modification in 30% and 74% of savolitinib and sunitinib patients, respectively.

Surufatinib, an oral selective inhibitor of vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), and colony stimulating factor-1 receptor (CSF-1R)

In clinical studies to date, involving over 900 patients, surufatinib has demonstrated robust efficacy and safety profile, including in two randomized, double-blind, placebo controlled, multi-center Phase III studies in pancreatic neuroendocrine tumor ("pNET") and non-pancreatic (extra-pancreatic) neuroendocrine tumor patients ("epNET"). In the U.S. surufatinib was granted Fast Track Designations for development in pNET and epNET, and Orphan Drug Designation for pancreatic NET. In China a New Drug Application ("NDA") is under review and a second is in preparation.

Presentation Title: Efficacy and safety of surufatinib in U.S. patients with neuroendocrine tumors ("NET")
Authors: A Dasari, D Li, MW Sung, C Tucci, JS Kauh, MK Kania, AS Paulson
Abstract Link: 4610
Preliminary data from the two NET cohorts in the ongoing US Phase Ib trial for surufatinib demonstrated promising efficacy irrespective of prior lines of therapy, with a manageable safety profile comparable with the larger pool of surufatinib safety data (NCT02549937).

As of April 21, 2020, 16 patients with pNET were treated for a median of 7.1 months (range 2.0-17.5) and 16 patients with epNET were treated for a median of 4.9 months (range of 1.0-10.2). All 32 patients have pretreated progressive NETs (median prior lines of treatment: 3; range 1-8).

Confirmed response was observed in 18.8% of pNET patients; all remaining patients have stable disease (including 1 unconfirmed response), for disease control rate ("DCR") of 100%. In the epNET cohort all patients had stable disease (including 1 unconfirmed response).

On May 29, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it has completed the secondary offering of 13,014,646 shares of its common stock held by Sanofi, which includes the exercise in full of the underwriters’ option to purchase additional shares from Sanofi, at a public offering price of $515.00 per share (Press release, Regeneron, MAY 29, 2020, View Source [SID1234558757]). The Company also announced the completion of its repurchase of 9,806,805 shares directly from Sanofi at a price of $509.85 per share (representing the price paid by the underwriters in the offering), for an aggregate purchase amount of $5 billion. Pursuant to the offering and repurchase, Sanofi has disposed of all of its shares of common stock in Regeneron, other than 400,000 shares that it is retaining.

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Regeneron did not receive any of the proceeds from the sale of shares of its common stock by Sanofi. The public offering occurred simultaneously in the United States and internationally through underwriters led by BofA Securities and Goldman Sachs & Co. LLC, together with Barclays, BNP Paribas, Citigroup, J.P. Morgan, Morgan Stanley as joint book-running managers.

Regeneron has filed a registration statement (including a prospectus) with the SEC for the offering. Before you invest, you should read the prospectus in that registration statement and other documents Regeneron has filed and will file with the SEC, including the final prospectus supplement dated May 26, 2020, for more complete information about Regeneron and this offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, any underwriter or any dealer participating in the offering will arrange to send you the prospectus and the prospectus supplement, if you request them by contacting BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at [email protected]; or Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, via telephone: 1-866-471-2526, or via email: [email protected].

On May 29, 2020 The University of Texas MD Anderson Cancer Center reported that results from a Phase I clinical trial led by researchers the adoptive T-cell therapy ADP-A2M4, which is engineered to express a T-cell receptor (TCR) directed against the MAGE-A4 cancer antigen, achieved responses in patients with multiple solid tumor types, including #102synovial sarcoma, head and neck cancer and lung cancer (Press release, MD Anderson, MAY 29, 2020, View Source [SID1234558773]).

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Among 38 patients treated on the trial, the ADP-A2M4 T cells resulted in overall response (OR), or tumor shrinkage, in 9 patients (23.7%) and stable disease in 18 patients (47.4%). Trial data were shared in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by principal investigator David Hong, M.D., professor of Investigational Cancer Therapeutics.

"Thus far, we haven’t seen strong responses in treating solid tumors with available cellular therapies, in large part because antigens expressed are not restricted to the tumors," said Hong. "In this trial, I’ve been encouraged to see durable responses in several patients, and the results suggest there is potential for this emerging TCR-based technology for treating solid tumors."

Adoptive cellular therapy is a form of immunotherapy that modifies immune cells to be more effective in mounting an immune response against cancer. For ADP-A2M4, T cells are isolated from patients and engineered to express a TCR targeting MAGE-A4, a protein normally expressed only in the testis but present in certain cancers.

Unlike chimeric antigen receptor (CAR)-modified T cells, which target surface proteins on cancer cells, TCR T-cell therapies are able to target proteins normally found inside the cell by recognizing protein fragments bound to immune-related proteins on the cell surface.

The Phase I trial was designed as a dose-escalation study to assess the safety, tolerability and antitumor activity of ADP-A2M4 in patients with advanced solid tumors with expression of the MAGE-A4 protein. Patients on the trial included those with synovial sarcoma, ovarian cancer, head and neck cancer, gastric cancer, myxoid/round cell liposarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer and melanoma. Participants had a median of three prior lines of systemic therapy.

The therapy achieved strong responses in particular groups of patients in the trial. Patients with synovial sarcoma saw a 43.8% OR rate and a disease control rate of more than 90%. There also was an additional patient with an unconfirmed response after the data cut-off. Median duration of response in these patients was 28 weeks and median progression-free survival was 20 weeks. Confirmed responses were also seen in patients with lung cancer and head and neck cancer.

Most patients (97.4%) experienced some treatment-related adverse events, with the most common being low blood cell counts (lymphopenia, leukopenia, neutropenia, anemia and thrombocytopenia). Half of patients experienced cytokine release syndrome. Two patients had trial-related deaths, which led to modification of the lymphodepletion regimen and eligibility criteria.

"The side effects seen on the trial were largely consistent with those typically experienced by cancer patients undergoing lymphodepleting chemotherapy and cellular therapy," said Hong. "This study is a nice proof of concept for treating solid tumors and suggests there could be a role for cellular therapies in these indications going forward."

This research is part of an ongoing strategic alliance between MD Anderson and Adaptimmune, designed to expedite the development of novel T-cell therapies for multiple cancer types. Translational research and analyses of related biomarkers continues. Results from this study led to a low-dose radiation sub-study, a Phase II trial of ADP-A2M4 in sarcoma and a Phase I trial of Adaptimmune’s next-generation T-cell therapy targeting MAGE-A4, ADP-A2M4CD8.