On December 3, 2018 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that Professor Paul G. Richardson presented updated interim data with melflufen (Ygalo) from the ongoing HORIZON trial at the 60th ASH (Free ASH Whitepaper) meeting in San Diego, California, USA (Press release, Oncopeptides, DEC 3, 2018, View Source [SID1234531865]).

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Overall conclusions

The updated phase II data with melflufen in late-stage relapsed-refractory multiple myeloma patients refractory to pomalidomide and/or daratumumab after failing on immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) shows:

An Overall Response Rate (ORR) of 33%, in patients where 46% had received 3+ regimens of treatments over the last 12 months
A vast majority of patients, 84%, achieved disease stabilization (SD or better)
The first evaluation of Progression Free Survival (PFS) shows a median of 4.0 months in the ongoing trial with a median of 6.4 months for responding patients
Activity was observed regardless of underlying refractory status and the traditional prognostic factor albumin was a strong predictor of ORR
The treatment was well tolerated with mainly reversible and manageable hematological adverse events. The incidence of non-hematological toxicity was low
Professor Paul G. Richardson comments

"Over the last decade, initial treatments in myeloma have been radically improved, and in particular with the advent of the widespread adoption of novel agent combination approaches as well as continuous therapy. However, the number of patients who become resistant to immunomodulatory agents, proteasome inhibitors and anti-CD38 monoclonal antibodies is increasing, and there is thus a clear need for effective treatment options with new mechanisms of action. Melflufen is a first in class peptidase-enhanced compound that does not share resistance pathways seen with currently used treatments and has general manageable toxicity with favorable tolerability. Melflufen is showing considerable promise in the relapsed and refractory setting, with clinical development ongoing" said Paul Richardson MD, the RJ Corman Professor of Medicine at Harvard Medical School and Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, USA.

About the HORIZON study

Patient recruitment to the study is ongoing. The interim data presented at the ASH (Free ASH Whitepaper) meeting is based on a data cut-off dated October 22ed 2018 with 83 patients treated and 82 patients included in the response analysis. The patients in the study are refractory to pomalidomide and/or daratumumab after failing on IMiDs and PIs.

Summary of the HORIZON interim data

The study continues to develop positively in this heavily pretreated patient group that is refractory to pomalidomide and/or daratumumab after failing on IMiDs and PIs with few remaining treatment options.

61% of patients in the study had high-risk cytogenetics, 36% of patients were ISS stage III, the median number of prior lines of therapy was 5 and the median time since initial diagnosis was 6.5 years.
All patients in the study were investigator assessed as non-responsive or non-tolerant to IMiDs and PIs, 100% of patients were also refractory to pomalidomide or daratumumab, 60% were refractory to IMiDs, PIs and anti-CD38, 55% were alkylator refractory and 93% had disease progression on or within 60 days of completion of the last therapy.
Analysis of the preliminary efficacy results showed an ORR of 32,9% and that 84,1% of the patients achieved disease stabilization (SD or better).
Overall response rate (N=82)
ORR sCR VGPR PR MR SD PD NE
total, N=82 32,9% 1,2% 11% 20,7% 6,1% 45,1% 14,6% 1,2%
Subgroup analysis suggests that response does not vary across refractory subsets but rather with the underlying disease and health status of the patient (confirming the observation made in Oncopeptides phase II study O-12-M1).
This study confirms earlier results from the O-12-M1 study in a more resistant patient population. The efficacy results in this interim analysis are encouraging with an ORR of 32,9%.

Melflufen showed a manageable safety and tolerability profile. Treatment-related grade 3/4 AEs were reported in 62 (75%) patients with the majority being hematological. Treatment-related non-hematological grade 3/4 AEs were rare with infections in only 7% of patients. 13% of the patients discontinued treatment due to AEs.

About melflufen

Melflufen (Ygalo), a peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Melflufen selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Melflufen in clinical development

Melflufen (Ygalo) has been used to treat late-stage RRMM patients in both phase I and phase II clinical studies (O-12-M1) with favorable results. Currently, melflufen is being studied in four clinical trials for the treatment of multiple myeloma. The current studies are OCEAN, HORIZON, ANCHOR and BRIDGE.

The current clinical study program is intended to demonstrate better results from treatment with melflufen compared to established alternative drugs for patients with late-stage multiple myeloma. Melflufen could potentially provide physicians with a new treatment option for patients suffering from this serious disease.

Melflufen has been investigated in the treatment of late-stage relapsed refractory multiple myeloma (RRMM) patients. This was done in the clinical study O-12-M1 where strong final results were reported in December 2017. Currently, four clinical studies are ongoing with melflufen.

OCEAN is Oncopeptides´ pivotal Phase III study where melflufen is compared directly with current standard of care, pomalidomide, in late-stage RRMM patients.

HORIZON is a Phase II study that studies the effect of melflufen in late-stage RRMM patients with few or no remaining established treatment options. Updated interim data from this study were presented at ASH (Free ASH Whitepaper) in December 2018.

ANCHOR is a phase I/II study where melflufen is administered in combination with either bortezomib or daratumumab in RRMM patients. The results of this study aim to create understanding and knowledge among treating physicians for how melflufen can be used in combination with these drugs. In addition, the results could open up for the use of melflufen in earlier lines of treatment. The first interim data from the study was presented in a poster presentation on December 1, 2018 at ASH (Free ASH Whitepaper).

BRIDGE is a phase II study, where melflufen is used in RRMM patients with impaired renal function. This is a positioning study to show melflufen’s treatment profile in these patients.

On December 3, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported results presented by collaborators at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. One study presents details of a next-generation CAR T technology that increases T cell persistence and decreases T cell exhaustion (Press release, Atara Biotherapeutics, DEC 3, 2018, View Source [SID1234531881]). Another important study presents positive Phase 2 clinical results in patients with EBV+ PTLD involving the CNS. PTLD patient treatment patterns and health outcomes are described in additional ASH (Free ASH Whitepaper) presentations.

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"Our highlighted ASH (Free ASH Whitepaper) presentations this year demonstrate the promise of Atara’s next-generation CAR T and off-the-shelf, allogeneic T-cell immunotherapy pipeline," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Cutting-edge CAR T discoveries by our Moffitt Cancer Center collaborators may have wide applications including as a component of our CAR T programs in acute myeloid leukemia (AML) and B-cell malignancies. Our collaborating investigators at Memorial Sloan Kettering also showed promising Phase 2 clinical results for patients with EBV+ PTLD involving the CNS, a difficult-to-treat and often lethal complication of bone marrow and organ transplantation. We are encouraged by these robust results and the broad potential of our CAR T technologies and T cell immunotherapy platform."

60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting Summary:

Abstract 966: Mutation of the CD28 Costimulatory Domain Confers Increased CAR T Cell Persistence and Decreased Exhaustion
Session: 703. Adoptive Immunotherapy: Preclinical Studies to Improve Safety and Efficacy of CAR-T Cells
Oral Presentation Date and Time: Monday, December 3, 2018 at 5:45 pm PST
Location: Marriott Marquis San Diego Marina, San Diego Ballroom B
Authors: Justin C Boucher, Gongbo Li, Bishwas Shrestha, Maria L Cabral, Dylan Morrissey, Lawrence Guan, Marco L Davila
Affiliations:Moffitt Cancer Center

Abstract 4590: Adoptive Therapy with EBV-Specific T Cells for Treatment of CNS EBV Post-Transplant Lymphoproliferative Disease Arising after Hematopoietic Stem Cell Transplant or Solid Organ Transplant
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Susan Prockop, MD, Stephanie Suser, Ekaterina Doubrovina, MD, PhD, Hugo R. Castro-Malaspina, MD, Esperanza B. Papadopoulos, MD, James W. Young, MD, Victoria Szenes, PNP, Alison Slocum, MA, Karim Baroudy, MS and Richard J. O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center
Overview:

This poster presentation evaluated EBV-specific T-cells generated from primary and third party (tab-cel) donors.
Patients with EBV+ PTLD involving the CNS following allogeneic hematopoietic stem cell transplant (HCT) or solid organ transplant (SOT) who failed prior rituximab from the Phase 2 studies 95-024 (NCT00002663) and 11-130 (NCT01498484) were included in the analysis.
Abstract 4777: Treatment Patterns for Patients with Post-Transplant Lymphoproliferative Disorder Who Fail Rituximab after Allogeneic Hematopoietic Stem Cell Transplantation: Findings from a Systematic Literature Review
Session: 902. Health Services Research—Malignant Diseases: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Hairong Xu, MD, PhD, Crystal Watson, MS, Shan Ashton Garib, MA, Anna Forsythe, PharmD, MSc, MBA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 3556: Estimating Long-Term Survival in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients
Session: 902. Health Services Research—Malignant Diseases: Poster II
Poster Presentation Date & Time: Sunday, December 2, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Stephen Palmer, MSc, Casey Quinn, PhD, MPhil, Crystal Watson, MS and Arie Barlev, PharmD
Affiliations:Centre for Health Economics, University of York, PRMA Consulting Ltd., Atara Biotherapeutics

Abstract 4596: Dual-Sensitized T-Cells Responding to EBV Blcl and Either CMVpp65 or WT-1 Peptide Pools Have Distinct or Shared HLA Restrictions That May Depend on the Presenting HLA Alleles
Session: 723. Clinical Allogeneic and Autologous Transplantation
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: San Diego Convention Center, Hall GH
Authors: Ekaterina Doubrovina, MD, PhD, Aisha N. Hasan, MD, Susan Prockop, MD, Karim Baroudy, MS, and Richard O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center

Abstract 5839: A Systematic Literature Review of Real-World Evidence in Post-Transplant Lymphoproliferative Disorder
Authors: Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Arie Barlev, PharmD, Nazia Rashid, PharmD and Crystal Watson, MS
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5841: Younger Patients Are Impacted By Post-Transplant Lymphoproliferative Disorder: Findings from a Systematic Literature Review of Real-World Evidence
Authors: Crystal Watson, MS, Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Shan Ashton Garib, MA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5840: Risk of Patients Developing Post-Transplant Lymphoproliferative Disorder within the First Year after an Allogeneic Hemopoietic Stem Cell Transplant, 2011 to 2016: A US Claims Database Analysis
Authors: Arie Barlev, PharmD, Hairong Xu, MD, PhD, Nicole Fulcher, MA, Crystal Watson, MS, Ila Sruti, MPH and Akshay Sudhindra, MD
Affiliations:Atara Biotherapeutics, IBM Watson Health

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab are considered to have increased risk for chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is estimated to be 36% and 0%, respectively.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, the FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC.

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]).

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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.

On December 3, 2018 NantKwest Inc. (Nasdaq:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, reported an abstract/poster presentations will be given at the upcoming 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA, which runs from December 1-4, 2018 (Press release, NantKwest, DEC 3, 2018, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-present-updated-preclinical-data-60th-annual-meeting [SID1234531832]).

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Presentation Title: Providing a Homing Receptor for CAR Engineered NK Cells – Improving Cellular Immunotherapy for B-Cell Lymphoma

Abstract: #4547

Presenter:Nathan Thomas Schomer, Laurent Boissel, Karen Jiang, Hans Klingemann, John Lee, and Patrick Soon-Shiong, NantKwest, Inc., Culver City, CA

Date:Monday, December 3, 2018, 6:00-8:00pm

Location:San Diego Convention Center, Hall GH

Presentation Highlights

NantKwest’s proprietary natural killer (NK) therapy is based on an activated natural killer cell platform (aNK) derived from a novel cell line with potent cytotoxicity. With over 400 doses safely administered to over 80 patients across multiple Phase I/II clinical trials, NantKwest’s off-the-shelf therapies have demonstrated encouraging clinical responses across a broad range of cancer cell types.

The company’s haNK cells, currently in multiple human clinical trials, have been engineered to carry a high-affinity version of the CD16/FcγRIII receptor that binds to the Fc portion of a monoclonal antibody to enhance the cancer cell killing effect when used in combination with haNK cell therapy.

As part of our next-generation NK cell therapy program, we further enhanced the potential targeting and homing efficiency of haNK cell therapy by incorporating both a CD19-targeting CAR, together with the chemokine-homing receptor, C-C Chemokine Receptor Type 7 (CCR7), which targets both Chemokine (C-C motif) ligand CCL19 (CCL19) and Chemokine (C-C motif) ligand 21 (CCL21), key signaling molecules expressed in lymph nodes to guide homing to these tissues. This tri-targeting NK cell therapy is designed to maximize NK cell activity by increasing NK cell migration to tumor sites and enhance cancer cell killing activity through both CD19-targeted, CAR-mediated killing, together with antibody mediated killing when combined with monoclonal clonal antibodies such as Rituximab.

Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest commented, "We look forward to reporting preclinical data on this novel tri-specific, off-the-shelf, homing CD19.t-haNK cell therapy. By engineering a novel chemokine-based CAR, into our off-the-shelf NK cell platform, we show that we can increase NK cell migration to target cancer cells and this enhanced homing can potentially maximize NK cell-driven immunogenic cell death. Representing what we believe will be an attractive treatment option, we are now focused on transitioning this next-generation NK cell therapy program to human clinical trials as rapidly as possible."

On December 3, 2018 Kite, a Gilead Company (Nasdaq: GILD), reported its updated results from ZUMA-3, a single-arm Phase 1/2 study evaluating KTE-X19 (formerly KTE-C19), an investigational CD19 chimeric antigen receptor T (CAR T) cell therapy, in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) (Press release, Kite Pharma, DEC 3, 2018, View Source [SID1234531849]). With a median follow-up of 15.1 months (range 3.7 – 28.6 months) following a single infusion of KTE-X19, 69 percent of evaluable patients (n=25/36) achieved complete tumor remission, defined as complete remission (CR) or CR with incomplete hematological recovery (CRi). The rate of undetectable minimal residual disease (MRD) in patients who achieved complete tumor remission was 100 percent. Detailed results from this ongoing study were presented today at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH; Abstract #897).

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"We are encouraged by the high number of patients who achieved complete leukemia remission following a single KTE-X19 infusion on this trial," said William G. Wierda, MD, PhD, Executive Medical Director and Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. "In relapsed and refractory ALL, where the majority of adult patients have poor response to treatment and short remissions and survival, these findings give optimism for improving outcomes and potentially showing clinical benefit for those affected by ALL."

Adverse events were consistent with the known toxicities of CD19 CAR T treatment, including Grade 3 or higher cytokine release syndrome (CRS) and neurologic events in 23 percent (n=10/44) and 39 percent (n=17/44) of patients, respectively. The majority of these adverse events were resolved, with the exception of two patients who had ongoing neurological events at the time of death from other causes. Two patients died from adverse events deemed by the treating investigator to be related to KTE-X19.

"These updated results from ZUMA-3 provide continued support for the potential of our CD19-directed CAR T therapies in new types of cancers and reinforce our leadership in cell therapy," said Alessandro Riva, MD, Executive Vice President, Oncology Therapeutics and Head, Cell Therapy, Gilead Sciences. "Based on these findings, we have initiated Phase 2 of the study evaluating KTE-X19 in a larger set of adult patients with ALL who are in need of new treatment options."

KTE-X19 is an investigational agent that has not been approved for any uses. Efficacy and safety have not been established.

About ALL

ALL is an aggressive type of blood cancer which can also involve the lymph nodes, spleen, liver, central nervous system and other organs.

About ZUMA-3

ZUMA-3 is an ongoing multicenter, registrational Phase 1/2 study in adult patients (≥18) with ALL whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation. The objectives of the study are to evaluate the safety and efficacy of KTE-X19 in this patient population.