1stOncology™: Cancer Intelligence Service – Page 14508 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Astellas Presents Updated Results from Phase 1 Study of Gilteritinib Plus Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)

On December 3, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported updated results from a Phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in patients newly diagnosed with FLT3 mutation-positive (FLT3mut+) Acute Myeloid Leukemia (AML) (Press release, Astellas, DEC 3, 2018, View Source [SID1234531821]). The data were presented today in an oral presentation (Abstract 564) at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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!

"A diagnosis of AML can be devastating for patients. It is a life-threatening disease and treatment usually needs to start as quickly as possible," said Keith W. Pratz, M.D., of John Hopkins Sidney Kimmel Comprehensive Cancer Center, who presented the data at the ASH (Free ASH Whitepaper) Annual Meeting. "Typical treatment for AML consists of induction and consolidation therapy. However, treatment options targeted for specific mutations may be important tools in physicians’ armamentarium of therapies for patients with AML. These results help advance our scientific understanding of how to potentially address these mutations in first-line treatment of AML."

The purpose of this ongoing, open-label dose escalation/expansion Phase 1 clinical study (NCT02236013) is to assess the safety, tolerability and antitumor effects of gilteritinib when combined with induction and consolidation chemotherapy, and as single-agent maintenance therapy, in adult patients with newly diagnosed AML.1

The two-part trial first enrolled patients to successive cohorts to determine the Maximum Tolerated Dose. Patients in the dose expansion cohort received gilteritinib at the recommended expansion dose established during dose escalation.

As of October 11, 2018, 68 subjects had been enrolled in the study; 66 are included in the safety analysis set. Of these patients, 36 (54.5%) had FLT3 mutations (FLT3-ITD, n=26). During dose-escalation, two patients in the 40 mg/day cohort who had received gilteritinib on days 1-14 experienced dose-limiting toxicities (DLTs; neutropenia, thrombocytopenia, decreased ejection fraction). After the gilteritinib induction schedule change, no more DLTs occurred at this dose. Two patients in the 200 mg/day cohort experienced DLTs (neutropenia, neutropenic enterocolitis). The maximum tolerated dose and the recommended expansion dose were established at 120 mg/day.

Additional key findings include:

The end-of-treatment investigator-reported rate of composite complete remission (CRc) for response evaluable FLT3mut+ subjects receiving gilteritinib 120 mg on Schedule 1 (n=17) was 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with daunorubicin was also 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with idarubicin was 66.7%.
Among subjects who received ≥80 mg/day gilteritinib (n=52), the CRc rate for FLT3mut+ subjects was 90.3% (n=28/31).
Median overall survival has not been reached. Median disease-free survival was 430 days (95% CI: 155, 630).
Grade ≥3 adverse events (AEs) in ≥10% of subjects were febrile neutropenia (63.6%), thrombocytopenia (19.7%), decreased platelet count (19.7%), decreased white blood cell count (19.7%), neutropenia (19.7%), decreased neutrophil count (16.7%), anemia (13.6%), and sepsis (10.6%).
Serious drug-related AEs in >1 subject were febrile neutropenia (n=11), sepsis (n=4), small intestinal obstruction, and decreased ejection fraction (both n=2).
Gilteritinib, under the brand name XOSPATA, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test.2 Gilteritinib is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a cancer that impacts the blood and bone marrow, and its incidence increases with age. The American Cancer Society estimates that in 2018, approximately 19,000 new patients will be diagnosed with AML in the U.S.3

About XOSPATA
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.2 XOSPATA is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize XOSPATA.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions

Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure, which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

ArQule Announces Clinical Data from Ongoing Phase 1 Study of Reversible BTK Inhibitor, ARQ 531, in Patients with Relapsed/Refractory Hematologic Malignancies at the 2018 ASH Annual Meeting

On December 3, 2018 ArQule, Inc. (Nasdaq: ARQL) reported its presented preliminary results from the Company’s Phase 1 dose escalation study for ARQ 531, an orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or refractory hematologic malignancies at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, ArQule, DEC 3, 2018, View Source [SID1234531820]).

Dr. Brian Schwartz, Chief Medical Officer of ArQule commented, "We are encouraged by the pace at which this trial is progressing and by the level of target engagement we are observing as we continue to dose escalate. Four out of the five heavily pretreated CLL patients enrolled in the last two cohorts with the BTK-C481S mutation have experienced tumor shrinkage."

"These data provide further evidence of ARQ 531’s potential to become a new therapeutic option for patients with B cell malignancies," commented Paolo Pucci, Chief Executive Officer of ArQule. "There is significant unmet need for patients with relapsed or refractory B-cell malignancies in particular those with the C481S-mediated resistance to irreversible BTK inhibitors such as ibrutinib."

The reported data are from the ongoing Phase 1, open label, single arm dose escalation 3+3 study and include the first six cohorts (n=20) at dose levels of 5, 10, 15, 20, 30 and 45 mg once a day in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Waldenstrom’s macroglobinemia and B-cell Non-Hodgkin lymphomas.

Key findings presented include the following:

ARQ 531 has demonstrated a manageable safety profile with no dose-limiting toxicities observed to date
Pharmacokinetic data are nearly dose proportional with a mean plasma half-life that supports QD dosing
Pharmacodynamic biomarkers for cohorts 4 through 6 showed profound pBTK inhibition
Anti-tumor activity, with reduction of tumor burden, was observed in 9 out of 20 patients
At the first assessment of tumor response, 80% of the ibrutinib refractory, heavily pretreated CLL patients (4 out of 5) in the highest dose cohorts (30 and 45 mg) experienced tumor shrinkages
Four out of 5 lymphoma patients derived benefit with shrinkages between 27 and 58%, including 1 PR in a Follicular Lymphoma patient who began at 5 mg, was dose escalated to 15 and then 45 mg, and remains on therapy after 70 weeks
The study is on-going and dose escalation continues
The presented poster, A Phase 1 Dose Escalation Study of ARQ 531 in Selected Patients with Relapsed or Refractory Hematologic Malignancies, is available on the company’s website at View Source

The Company will hold a conference call and webcast today at 9:00 a.m. ET to discuss these results. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events & Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events and Presentations."

About BTK and ARQ 531

Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers. ARQ 531 is an orally bioavailable, potent and reversible BTK inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S-mutation is a known resistance mechanism for first generation irreversible BTK inhibitors. In preclinical studies, ARQ 531 has demonstrated good oral bioavailability as well as favorable pharmacokinetic, pharmacodynamic and metabolic properties.

Onconova Highlights Results from Phase 2 Trial of Oral Rigosertib In Combination with Azacitidine (Vidaza®) in Myelodysplastic Syndromes (MDS) at the 2018 ASH Annual Meeting

On December 3, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the presentation of the efficacy and safety results of oral rigosertib in combination with azacitidine (Vidaza) in patients with HR-MDS reported at an oral presentation during the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego (Press release, Onconova, DEC 3, 2018, View Source [SID1234531818]). Rigosertib, the Company’s lead compound, is being evaluated in both intravenous and oral forms.

ORAL PRESENTATION:

Phase 2 Expansion Study of Oral Rigosertib Combined with Azacitidine treatment in Patients with Higher-Risk (HR) Myelodysplastic Syndromes (MDS): Efficacy and Safety Results in HMA Treatment Naïve & Relapsed (Rel)/Refractory (Ref) Patients

Session Name: 637. Myelodysplastic Syndromes — Clinical Studies: Novel Therapeutics I

Date: Saturday, December 1, 2018

Presentation Time: 4:15 PM PST

Seventy-four (74) patients were treated with a median age of 69 years (range 42-90) at 9 clinical sites, and received either 840 mg or 1,120 mg of oral rigosertib daily divided into two doses, in combination with a standard dose of injectable azacitidine. Of the 55 evaluable patients, 29 patients were treated with a daily dose of 1,120 mg of oral rigosertib, either 560 mg twice daily (12 patients) or 840 mg in the a.m. and 280 mg in the afternoon (17 patients). Twenty-six patients were treated with 560 mg in the AM and 280 mg in the PM (daily dose of 840 mg) for the first three weeks of a four-week cycle. All patients also received 75 mg/m2/day SC or IV azacitidine during the second week of the four-week cycle. The median duration of treatment for the HMA naïve and HMA failed patients was 7.8 and 4.9 months respectively. The median duration of response in these groups was 12.2 and 10.8 months, respectively.

The overall response rate (ORR) using the IWG 2006 criteria, in 29 HMA naïve patients, was 90%; including 10 patients (34%) with Complete Remission (CR). Among the 26 evaluable HMA-

failed patients the ORR was 54% including 8% CR or PR. The median time to initial and best response were 1 and 4 cycles in the HMA naïve group and 2 and 5 cycles in the HMA failed group.

The safety population (n = 74) received at least 1 dose of oral rigosertib. The combination was well tolerated. Other than genitourinary adverse events (AEs), the AE profile was similar to those described for azacitidine alone in this patient population. Genitourinary AEs, including hematuria (45% incidence of all grades, including 9% grade 3, and dysuria (38% all grades and 9% grade 3) were observed. A Safety Optimization Strategy was implemented for the higher dose cohort of 1,120 mg of oral rigosertib. These strategies included earlier in the day administration of the PM dose, oral hydration, monitoring of urinary pH and mandatory bladder emptying at night. Collectively these strategies resulted in mitigation of the target genitourinary AEs, including reduction of genitourinary grade 3 AEs reported from an earlier cohort despite receiving a higher dose of oral rigosertib.

In conclusion, oral rigosertib in combination with azacitidine was well tolerated in HMA naïve and HMA failed HR-MDS patients. The combination produced an encouraging rate of overall response and complete remission in both groups. The safety optimization strategies and increased dose exploration of oral rigosertib in the combination is leading to the development of a pivotal Phase 3 trial in HMA and chemotherapy naïve patients.

Drs. Lewis Silverman and Guillermo Garcia Manero, the lead investigators of the study at Mount Sinai Medical Center and MD Anderson Cancer Center, respectively, commented, "This multi-institutional collaborative study based on earlier laboratory research showing synergistic activity of rigosertib in combination with azacitidine led to a clinical trial of this combination in higher-risk MDS patients for both HMA naive and failed patients. The high overall response rate reported today is impressive, as is the durability and rate of achieving complete remission. We are excited about progressing these studies to a randomized pivotal placebo-controlled Phase 3 trial. The overall tolerability of the combination and convenience of administration of oral rigosertib could be key advantages for these future studies."

Dr. Steve Fruchtman, President of Onconova Therapeutics, Inc, sponsor of this study and developer of rigosertib commented, "We are most grateful to the patients, their families and our dedicated collaborating investigators for their participation in this study. The impressive results presented here have led to our plan for a pivotal trial for these patients ultimately hoping to improve upon their current therapeutic options. Based on End of Phase 2 Meetings with the Health Authorities, we have developed a randomized controlled pivotal trial. We expect to start the regulatory process for the approval of this trial plan very shortly. We are hopeful that both intravenous and oral formulations of rigosertib will be useful in serving the needs of higher risk MDS patients".

This oral presentation was delivered by Shyamala Navada, MD, Mount Sinai Medical Center on Saturday, December 1, 2018.

A copy of the presentation is available by visiting the Scientific Presentations section of Onconova’s website.

Onconova plans to meet with the FDA to discuss the results of the Phase 2 trial and the planned Phase 3 trial, and to seek a Special Protocol Assessment. The Company has partnered rigosertib with SymBio Pharmaceuticals, for Japan and Korea, and with Pint Pharma for Latin American countries. Both partners have indicated their interest in participating in the proposed new pivotal Phase 3 trial by enrolling patients in their respective territories. SymBio is currently conducting Phase 1 studies with oral rigosertib in Japan and also participating in the Phase 3 global INSPIRE trial. The Company is also actively seeking additional collaborations for rigosertib in other geographies.

Oncolytics Biotech® Announces Increased PD-L1 Expression When Combining Pelareorep with a Proteasome Inhibitor in Poster Presentation at the 60th American Society of Hematology Annual Meeting & Exposition

On December 3, 2018 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported a poster presentation made at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition taking place December 1-4 in San Diego, California (Press release, Oncolytics Biotech, DEC 3, 2018, View Source [SID1234531817]). The poster highlights pelareorep’s ability to increase PD-L1 expression on tumor cells in patients with relapsed myeloma.

The poster, authored by Craig C. Hofmeister, Acting Associate Professor, Department of Hematology and Medical Oncology Emory University School of Medicine, et al., is titled "Oncolytics Virus Replication Using Pelareorep and Carfilzomib in Relapsed Myeloma Patients Increases PD-L1 Expression with Clinical Responses", was presented yesterday. This phase 1 study enrolled 15 patients with relapsed myeloma.

"There is a growing effort to identify agents that can upregulate PD-L1 to increase the potential number of patients that can be treated with immune checkpoint blockade," said Dr. Hofmeister. "The data in this poster clearly demonstrate an increase in viral infection and viral replication, as well as pelareorep-dependent PD-L1 increased expression on the surface of myeloma cells, among patients undergoing treatment with pelareorep in combination with carfilzomib."

Highlights from the Poster:

Responses include:

Three very good partial responses (at least 90% reduction in monoclonal protein)

Three partial remissions (at least 50% reduction in monoclonal protein)

Three minimal responses (between 25% and 50% response to a drug or regimen in a clinical trial

Three stable disease

In patients receiving pelareorep with a clinical response, there was simultaneous CD8, PD-L1, and NK cell response, as well as activated caspase-3 expression

In patients treated with pelareorep, PD-L1 expression increased significantly more in patients with clinical response

"This presentation adds to the growing body of clinical evidence that pelareorep can boost PD-L1 expression and has the potential to be a backbone for immune checkpoint inhibition," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech. "We appreciate the continued support of Dr. Hofmeister and look forward to collecting additional data from his subsequent study combining pelareorep with Bristol Myers Squibb’s immune checkpoint inhibitor, Opdivo, which should begin enrollment before the end of the year."

The poster can be found at View Source

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia

On December 3, 2018 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported that it will share the detailed data from its Phase 2 clinical trial of efgartigimod (ARGX-113) in immune thrombocytopenia (ITP) and the Phase 1 portion of its Phase 1/2 clinical trial of cusatuzumab (ARGX-110) in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) during a workshop being held in conjunction with the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, argenx, DEC 3, 2018, View Source [SID1234531816]).

The workshop is being held on Monday, December 3, 2018 at 12:00 p.m. PT. A live webcast of the workshop will be available on argenx’s website at www.argenx.com. A replay of the webcast will be available for 90 days following the presentation.

"These datasets highlight the power of the collaborations we’ve forged with leading academic institutions. As part of these collaborations, we combine our antibody discovery capabilities with our collaborators’ deep disease biology insights to together unravel the functions of novel targets. We have built our broad pipeline in this way and have demonstrated strong execution with each new product candidate we bring forward. Based on the clinically meaningful results and clean tolerability profiles we have observed to date, we believe we have two antibody molecules with efgartigimod and cusatuzumab that are both first-in-class and potentially best-in-class," commented Tim Van Hauwermeiren, Chief Executive Officer of argenx.

"We established strong proof-of-concept with efgartigimod in a second autoimmune indication showing a clear correlation between IgG reductions, platelet count increases and reduced bleeding events. The improvements in platelet counts were clinically meaningful in the treatment arms after a short drug exposure in a truly refractory ITP patient population. With these results and the drug candidate’s continued favorable tolerability, we look forward to advancing into a potential pivotal trial next year," commented Nicolas Leupin, Chief Medical Officer of argenx.

Key ITP Clinical Results

This trial evaluated 38 adult patients with primary ITP who were inadequately controlled on standard of care (platelet count < 30 x109/L at screening) in a Phase 2 proof-of-concept trial of efgartigimod. Patients received 4 doses over 3 weeks of either 5 mg/kg or 10 mg/kg of intravenous (IV) efgartigimod, or placebo. The Phase 2 trial was amended in December 2017 to extend the patient follow-up period to 21 weeks and to include the option to enter an open-label extension (OLE) trial. Data being presented today are the full data set.

The primary endpoint was safety and tolerability; efgartigimod was well-tolerated in all patients, with most adverse events (AEs) characterized as mild and deemed unrelated to trial drug.

Clinically meaningful improvements in platelet counts were seen across ITP classifications and standard of care and included:

46% of patients improved platelet count to > 50×109/L during two or more visits in each of the 5 mg/kg and 10 mg/kg dosing cohorts compared to 25% in the placebo cohort.

Updated data show that 67% of patients in the OLE trial improved platelet count to > 50×109/L during two or more visits following the first dosing cycle. Responders from the 10 mg/kg arm in the primary trial all responded again upon retreatment in the OLE trial.

Onset of platelet count reaching 50×109/L for the first time ranged from week 1 to week 10, consistent with disease heterogeneity.

For efgartigimod-treated patients with clinically meaningful platelet responses (> 50×109/L during two or more visits), the mean duration of platelet response was 40 days versus 16 days for placebo treated patients, with responses lasting the trial duration.

38% of efgartigimod-treated patients showed durable platelet count improvements to clinically meaningful and statistically significant levels of > 50×109/L for at least 10 cumulative days, compared to 0% of placebo patients (p=0.03).

Lasting IgG reductions consistent with levels achieved in previous studies (updated results) included:

All efgartigimod-treated patients showed a rapid and deep reduction of total IgG levels, consistent with the pharmacodynamic effects observed in previous clinical trials. Reduction of IgG levels was consistent across IgG subtypes.

Reduction in platelet-associated autoantibodies observed in the majority of patients with clinically meaningful platelet increase.

Low titer of anti-drug antibodies was detected in 16.7% of placebo patients and 30.8% of treated patients in the 10 mg/kg arm with no apparent effect on pharmacokinetics or pharmacodynamics.

Bleeding events were assessed using three metrics—adverse event reporting, the WHO scale and the ITP-BAT scale—and showed that efgartigimod reduced bleeding events (updated results) across each scale including:

AE reporting showed no severe bleeding events in any patient, mild bleeding events only were reported in the 10 mg/kg arm and mild and moderate in the 5 mg/kg and placebo arm.

Incidence of bleeding events was reduced by efgartigimod treatment as assessed by the WHO bleeding scale, with separation from placebo as early as the third dose in the 10 mg/kg arm.

Incidence of bleeding events in the skin was reduced by efgartigimod treatment as assessed by the ITP-BAT bleeding scale, with no clear signal of bleeding events in the mucosa or organs in either treatment arm.

Efgartigimod treatment resulted in clear correlation between IgG reduction, platelet count improvement and bleeding event reduction.

Based on these data, argenx plans to advance efgartigimod (IV) to Phase 3 development in ITP. argenx also expects to initiate a Phase 2 trial in ITP using a subcutaneous formulation of efgartigimod.

Key AML Clinical Results

argenx evaluated 12 newly diagnosed AML patients unfit for intensive chemotherapy in the Phase 1 dose escalation part of the open-label Phase 1/2 clinical trial. Patients received cusatuzumab in combination with Vidaza. Data being presented today are updated as of the new cut-off date of October 15, 2018.

Cusatuzumab continued to be well-tolerated in AML patients on all four doses (1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg).

The data show an overall response rate (ORR) across the 12 patients of 92% (11/12 patients), including 10 patients (91%) with a complete remission with or without hematologic recovery (CR/CRi) and 1 (9%) partial remission (PR).

Responses were seen in patients across age and risk category, including IDH2 and TP53 mutations.

The median duration on trial as of data cut-off was 8.1 months, ranging from 2 to 17.4 months, with 6 patients still on trial.

Five patients (42%) achieved minimal residual disease (MRD) negativity as measured by flow cytometry and molecular genetics in the bone marrow.

Translational data demonstrated that cusatuzumab monotherapy and in combination with Vidaza significantly reduced leukemic stem cells in the bone marrow of AML patients.

argenx is currently enrolling an initial 21 AML patients in the Phase 2 part of its Phase 1/2 clinical trial using the 10 mg/kg dose of cusatuzumab.

"We continue to be excited by the encouraging dataset from our Phase 1/2 trial of cusatuzumab in AML and MDS. This agent targets the CD70/CD27 pathway which has the potential to be a novel and selective mechanism in treating newly diagnosed AML patents regardless of age or cytogenetic profile. Today we are seeing a growing depth of responses from patients on cusatuzumab, with 10 out of 12 patients reaching complete response and 8 of these 10 with hematologic recovery, which patients tolerated well. Six patients remain on trial, and we will watch as these data mature, including the durability of responses," added Nicolas Leupin, Chief Medical Officer of argenx.

About Efgartigimod

Efgartigimod (ARGX-113) is an investigational therapy for IgG-mediated autoimmune diseases and was designed to exploit the natural interaction between IgG antibodies and the recycling receptor FcRn. Efgartigimod is the Fc-portion of an IgG1 antibody that has been modified by the argenx proprietary ABDEG technology to increase its affinity for FcRn beyond that of normal IgG antibodies. As a result, efgartigimod blocks antibody recycling through FcRn binding and leads to fast depletion of the autoimmune disease-causing IgG autoantibodies. The development work on efgartigimod is conducted in close collaboration with Prof. E. Sally Ward (University of Texas Southwestern Medical and Texas A&M University Health Science Center, a part of Texas A&M University (TAMHSC)).

About Cusatuzumab

Cusatuzumab (ARGX-110) is an investigational SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. Cusatuzumab is designed to: block CD70, kill cancer cells expressing CD70 through complement dependent cytotoxicity, enhanced antibody-dependent cell-mediated phagocytosis and enhanced antibody-dependent cell-mediated cytotoxicity, and restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). Cusatuzumab is currently being evaluated in patients with hematological malignancies, including a Phase 1/2 trial in combination with Vidaza in patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes and the Phase 2 part of a Phase 1/2 trial in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Preclinical work on cusatuzumab in AML was performed in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won, together with Prof. Manz at the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.