On December 3, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported presentations highlighting updated data from the Phase 2b STORM study evaluating selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with penta-refractory multiple myeloma, and from two arms of the Phase 1b/2 STOMP study evaluating selinexor and dexamethasone in combination with standard approved therapies, Pomalyst (pomalidomide) or Darzalex (daratumumab), in patients with previously treated multiple myeloma (Press release, Karyopharm, DEC 3, 2018, View Source [SID1234531833]). The data were featured in oral and poster presentations at American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting taking place December 1-4, 2018 in San Diego. A New Drug Application (NDA) seeking accelerated approval for oral selinexor with low dose dexamethasone as a treatment for patients with penta-refractory multiple myeloma is under Priority Review by the U.S. Food and Drug Administration (FDA) with an action date of April 6, 2019, under the Prescription Drug User-Fee Act (PDUFA).

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"As an increasing number of myeloma patients experience progressive disease despite treatment with combination regimens, there is a growing need for new therapies, particularly those with novel mechanisms, to help treat patients with relapsed and/or refractory myeloma. The 26.2% ORR determined by the Independent Review Committee (IRC) in the STORM study is highly compelling and reinforces the potential of selinexor in this difficult to treat patient population," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "Additionally, the Phase 1b/2 STOMP study continues to generate encouraging efficacy and safety data from multiple ongoing arms evaluating once weekly oral selinexor and dexamethasone (dex) in combination with the standard approved therapies in patients with newly diagnosed and relapsed/refractory multiple myeloma. The data presented at this year’s ASH (Free ASH Whitepaper) annual meeting show impressive response rates across several high unmet need patient subgroups, including Darzalex-naïve or Pomalyst-naïve and Revlimid (lenalidomide)-relapsed or -refractory myeloma. Given the synergistic activity observed to date with once weekly oral selinexor plus these approved myeloma therapies, we continue to believe that selinexor holds tremendous potential as a future combination backbone therapy in myeloma."

Updated Phase 2b STORM Results

These clinical results are from Part 2 of the international, multi-center, single-arm Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) study, which enrolled 122 heavily pretreated patients (median of seven prior treatment regiments) with penta-refractory myeloma. Patients with penta-refractory myeloma have previously received the two proteasome inhibitors (PIs), Velcade (bortezomib) and Kyprolis (carfilzomib), the two immunomodulatory drugs (IMiDs), Revlimid and Pomalyst, and the anti-CD38 monoclonal antibody Darzalex, as well as alkylating agents, and their disease is refractory to glucocorticoids, at least one PI, at least one IMiD, Darzalex and their most recent therapy. Each patient started 80mg oral selinexor twice weekly in combination with low-dose dexamethasone (dex; 20mg twice weekly).

For the STORM study’s primary objective, oral selinexor achieved a 26.2% ORR, which included two stringent complete responses (sCRs), six very good partial responses (VGPRs) and 24 partial responses (PRs). The two sCRs were negative for minimal residual disease, one at the level of 1×10-6 and one at 1×10-4; this is particularly significant in this penta-refractory population. Both patients who had relapsed after CAR-T therapy achieved PRs. The ORR in patients who had previously received Darzalex combination therapy (n=86) was 29.1%. The disease control rate for patients who had achieved stable disease or better was 78.7%. All responses were confirmed by an IRC. Median progression-free survival (PFS) was 3.7 months and the median duration of response (DOR) was 4.4 months. Median overall survival (OS) across the study was 8.6 months. Median OS in the approximately 40% of patients with at least a minimum response (MR) on selinexor + dex was 15.6 months compared to a median OS of 1.7 months in patients whose disease progressed or where response was not evaluable (p<0.0001). The short median OS of patients with no response to selinexor is consistent with the lack of available effective therapies for the very heavily pretreated population who entered the study. Real world OS data were also obtained from the Flatiron Health Analytic Database (FHAD). These results further highlight the limited life-expectancy in patients with highly refractory multiple myeloma. OS data from the FHAD indicate that patients with triple-class refractory myeloma (n=69) had a median OS of 3.5 months, also consistent with previously reported data from the literature.

The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from Part 1 of this study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies. Most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (69%), fatigue (56%), anorexia (52%), and weight loss (47%) and mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 treatment-related AEs were thrombocytopenia (54%), anemia (29%), neutropenia (19%) and fatigue (19%). No significant major organ toxicities were observed, and bleeding and infection rates were low.

Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. A NDA seeking accelerated approval for oral selinexor with low dose dexamethasone as a new treatment for patients with penta-refractory multiple myeloma was accepted and filed with Priority Review by the U.S. FDA. The FDA assigned an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA). Provided marketing approval is granted by the FDA, Karyopharm plans to commercialize selinexor in the U.S. in the first half of 2019. The Company also plans to submit a Marketing Authorization Application to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval.

Updated Phase 1b/2 STOMP Study (Selinexor plus Darzalex and Low-dose Dexamethasone (SDd))

In this arm of the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study, oral selinexor (dose escalated using either 100mg once weekly or 60mg twice weekly) is being evaluated in combination with Darzalex (16mg/kg intravenously once weekly) and low dose dexamethasone (dex; orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory multiple myeloma who received at least three prior lines of therapy, including a PI and an IMiD, or patients with myeloma refractory to both a PI and an IMiD. The following table is a summary of the efficacy results:

Best Responses1 in Evaluable SDd Patients as of 15-Nov-20182
Category N3 ORR VGPR PR4
Darzalex naïve 24 19 (79%) 7 (29%) 12 (50%)
All 26 19 (73%) 7 (27%) 12 (46%)
Key: ORR=Overall Response Rate (VGPR+PR)
1 Responses were adjudicated according to the International Myeloma Working Group criteria
2 Based on interim unaudited data
3 Two patients were not evaluable for response withdrew consent prior to disease follow up
4 Two unconfirmed PR

Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID) refractory disease, only 19% of patients did not respond (≤stable disease). Median PFS and DOR have not been reached. Based on published data the expected ORR for Darzalex therapy without selinexor in the Darzalex-naïve population is ~30%. Thus, the ORR of 79% provides a basis for further evaluation of the SDd combination.

Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (60%), fatigue (48%), diarrhea (32%), vomiting (24%) and anorexia (28%) and mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 treatment-related AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%) and neutropenia (24%). No Grade 5 AEs were reported. The maximum tolerated dose was not reached. Two dose-limiting toxicities (DLTs) (Grade 3 thrombocytopenia and Grade 2 fatigue) were observed in patients receiving selinexor 60mg twice weekly. No DLTs were reported in the 100mg once weekly cohort. The longest duration of therapy is over 60 weeks. Based on these preliminary tolerability and efficacy data, the RP2D of SDd is selinexor (100mg orally, once weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, weekly).

Updated Phase 1b/2 STOMP Study (Selinexor plus Pomalyst and Low-dose Dexamethasone (SPd))

In this arm of the Phase 1b/2 STOMP study, oral selinexor is being evaluated in combination with Pomalyst (3 or 4mg orally, once daily) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory multiple myeloma who received at least three prior lines of therapy, including a PI and an IMiD, or patients with myeloma refractory to both a PI and an IMiD. The following table is a summary of the efficacy results:

Best Responses1 in Evaluable SPd Patients as of 15-Nov-20182
Prior Therapy Status N3 ORR VGPR PR4 Median PFS
Pomalyst-naïve and Revlimid refractory or relapsed 26 14 (54%) 5 (19%) 9 (35%) 12.2 months
Pomalyst and Revlimid refractory 8 3 (38%) - 3 (38%) 5.5 months
All 34 17 (50%) 5 (15%) 12 (35%) 12.2 months
Key: ORR=Overall Response Rate (VGPR+PR)
1 Responses were adjudicated according to the International Myeloma Working Group criteria
2 Based on interim unaudited data
3 Four patients not evaluable for response: one death unrelated to myeloma, one non-compliance with study procedures, two withdrawal of consent before disease follow up
4 One unconfirmed PR

Responses tended to occur rapidly with a median of one month to onset. Median PFS among all evaluable patients was 12.2 months, with a follow up of 9.4 months. Median PFS in Pomalyst and Revlimid-refractory myeloma was 5.5 months. Among patients with a PR or better (n=17), the median time on treatment was 9.4 months.

Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (53%), fatigue (50%) and weight decreased (34%). As expected, the most common treatment-related Grade 3 and 4 AEs were neutropenia (55%), thrombocytopenia (34%), anemia (29%) and leukopenia (18%). There were three Grade 5 treatment-related events (febrile neutropenia, intracranial hemorrhage and pneumonia). Based on these tolerability and efficacy data, doses of oral selinexor 60-80mg once weekly are being evaluated in combination with Pomalyst (3mg orally, once daily) and low dose dex to determine the RP2D for this combination regimen.

In parallel with the ongoing Phase 1b/2 STOMP study, Karyopharm is conducting the pivotal, randomized Phase 3 BOSTON study evaluating once weekly selinexor in combination with the proteasome inhibitor Velcade and dex (SVd) for the treatment of patients with multiple myeloma who have had one to three prior lines of therapy. The Company expects to complete enrollment in the BOSTON study by the end of 2018, with top-line data anticipated at the end of 2019. Assuming a positive outcome, Karyopharm plans to use the results from the BOSTON study to support an application for full approval of selinexor in relapsed/refractory multiple myeloma.

Details for the ASH (Free ASH Whitepaper) 2018 presentations highlighting the STORM and STOMP studies are as follows:

Title: Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory MM
Presenter: Ajai Chari, Icahn School of Medicine at Mount Sinai, New York, New York
Abstract Number/Publication ID: 598
Session: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies
Date and Time: Monday, December 3, 2018; 7:45 AM PT
Location: San Diego Convention Center, Room 6F

Title: Deep and Durable Responses with Selinexor, Daratumumab, and Dexamethasone (SDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs: Results of Phase 1b Study of SDd
Presenter: Cristina Gasparetto, Duke University Cancer Center, Durham, North Carolina
Abstract Number/Publication ID: 599
Session: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies
Date and Time: Monday, December 3, 2018; 8:00 AM PT
Location: San Diego Convention Center, Room 6F

Title: Selinexor Plus Pomalidomide and Low Dose Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma
Presenter: Christine Chen, Princess Margaret Cancer Center, Toronto, Ontario
Abstract Number/Publication ID: 1993
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Date and Time: Saturday, December 1, 2018; 6:15-8:15 PM PT
Location: San Diego Convention Center, Hall GH

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,800 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

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 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the presentation of preclinical data from the Company’s Menin-Mixed Lineage Leukemia (MLL) inhibitor program at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Syndax, DEC 3, 2018, View Source [SID1234531831]).

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"Acute leukemias characterized by MLL-rearrangements (MLL-r) and nucleophosmin (NPM1) mutations represent areas of high unmet medical need, with 5-year survival rates falling below 50%," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Data presented on VTP-50469, a Syndax Menin-MLL inhibitor, provides further support for developing this class of molecules for specific, genetically-defined acute leukemias. The robustness and consistency of the accumulated preclinical data seen with our Menin-MLL inhibitors provide support for an anticipated IND filing on our lead compound, SNDX-5613, in the second quarter of 2019."

In an oral presentation at ASH (Free ASH Whitepaper), Hannah Uckelmann, Ph.D., Dana-Farber Cancer Institute, presented new preclinical data demonstrating that NPM1 mutant progenitor cells can act as drivers of leukemic transformation, and that VTP-50469 can block their pathological capacity by disrupting the menin-MLL interaction. In addition, data generated using a mouse PDX model of NPM1 mutant acute myeloid leukemia (AML) demonstrated that single agent treatment with VTP-50469 eradicated pre-leukemic NPM1 mutant cells and prevented leukemia development, resulting in a marked survival benefit. These data lend further support to the potential therapeutic utility of menin inhibitors in the setting of NPM1 mutant AML.

Furthermore, during a Scientific Spotlight Session at ASH (Free ASH Whitepaper), Scott Armstrong, M.D., Ph.D., Dana-Farber Cancer Institute, provided an overview of the multiple complexes that influence gene expression in MLL-r leukemias and NPM1 AML. Additional preclinical data generated in his laboratory further substantiate that inhibition of the Menin-MLL interaction can decrease leukemic burden and prolong survival in mouse PDX models of both MLL-r and NPM1 mutant leukemias. These data build on prior encouraging preclinical results presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, and further underscore the potential therapeutic utility of menin inhibitors as modulators of critical epigenetic mechanisms in acute human leukemias, including subsets of both acute lymphoblastic leukemia (ALL) and AML.

Oral Presentation:

Title: MLL-Menin Inhibition Reverses Pre-Leukemic Progenitor Self-Renewal Induced By NPM1 Mutations and Prevents AML Development
Presenter: Hannah Uckelmann, Ph.D., Research Fellow at the Dana-Farber Cancer Institute
Publication Number: 546

Scientific Spotlight Session:

Title: Targeting Chromatin Complexes in MLL Rearranged Leukemia
Presenter: Scott Armstrong, M.D., Ph.D., Chairman of the Department of Pediatric Oncology at the Dana-Farber Cancer Institute, Associate Chief of the Division Hematology/Oncology at Boston Children’s Hospital, and the David G. Nathan Professor of Pediatrics at Harvard Medical School

Both presentations are available in the Publications section of the Company’s website, www.syndax.com.

About MLL Rearranged Leukemias

Rearrangements of the MLL gene give rise to an acute leukemia, MLL-r. MLL-r occurs in ~80% of infant acute leukemias and up to 10% of adult acute leukemias. It is associated with a poor prognosis, with less than 50% of infants with MLL-r surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with a protein called Menin in order to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias are routinely diagnosed through currently available cytogenetic screening techniques in leukemic cells, but there are currently no approved therapies indicated for MLL-r leukemias.

About NPM1c Acute Myeloid Leukemia

NPM1c represents another discrete form of acute myeloid leukemia (AML) distinguished by point mutations in the NPM1 gene that drives the leukemic phenotype. NPM1c is the most common type of cytogenetically normal AML and represents ~30% of all diagnosed AML. This subtype of AML has a poor prognosis, with a 5-year overall survival rate of ~50%. Similar to MLL-r leukemias, NPM1c AML is highly dependent on the expression of specific developmental genes, shown to be negatively impacted by inhibitors of the menin-MLL1 interaction. NPM1c AML is routinely diagnosed through currently available screening techniques in leukemic cells, but there are currently no approved therapies indicated for NPM1c AML.

On December 3, 2018 TRACON Pharmaceuticals (Nasdaq: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, and I-Mab Biopharma ("I-Mab"), a China-based clinical stage biopharmaceutical company exclusively focused on the development of innovative biologics in immuno-oncology and autoimmune diseases, will host a conference call and webcast on Wednesday, December 5, 2018, to discuss the recently announced series of strategic collaborative partnerships for developing multiple immuno-oncology programs (Press release, Tracon Pharmaceuticals, DEC 3, 2018, http://ir.traconpharma.com/news-releases/news-release-details/tracon-pharmaceuticals-and-i-mab-biopharma-host-conference-call [SID1234531830]).

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Wednesday, December 5th @ 4:30pm Eastern Time
US Investors: 877-407-9039
International: 201-689-8470
Passcode: 13685586
Webcast: View Source

Replays, Available through December 19th:
Domestic: 844-512-2921
International: 412-317-6671
Replay PIN: 13685586
About TRACON
TRACON develops targeted therapies for cancer and ophthalmic diseases. The Company’s clinical-stage pipeline includes: TRC105, an endoglin antibody that is being developed for the treatment of multiple cancers; DE-122, the ophthalmic formulation of TRC105 that is being developed in wet AMD by corporate partner Santen Pharmaceutical Company Ltd.; TRC102, a small molecule being developed for the treatment of lung cancer and solid tumors; and TRC253, a small molecule being developed for the treatment of prostate cancer. To learn more about TRACON and its product candidates, visit TRACON’s website at www.traconpharma.com.

About I-Mab
I-Mab is a dynamic and fast-growing global company exclusively focused on developing first-in-class and best-in-class biologics in the areas of immuno-oncology and autoimmune diseases through internal R&D capabilities and global partnerships. I-Mab’s pipeline is driven by the company’s development strategy to address unmet needs in China and to bring innovative assets to the world. The company is prepared to submit additional INDs in order to initiate clinical trials in China and the U.S., including multiple Phase II and Phase III studies. I-Mab is on a fast track towards becoming an end-to-end fully integrated biopharma company. The company has been well-recognized by capital markets with the recent $220 million Series C financing representing one of the largest amounts ever raised by an innovative biotech company in China. www.i-mabbiopharma.com

On December 3, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or "the Company"), reported that updated data from its Phase 2 trial of Actimab-A was highlighted in a poster presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, DEC 3, 2018, View Source [SID1234531829]). The Actimab-A Phase 2 trial studied the ARC or Antibody Radiation Conjugate Actinium-225 – lintuzumab, which delivers potent alpha particle radiation to CD33 expressing cells, in patients with untreated AML over the age of 60 that are unfit for induction chemotherapy. Patients received fractionated doses of Ac-225 – lintuzumab on days 1 and day 8. The poster presented at ASH (Free ASH Whitepaper) highlighted data from a second cohort of 27 patients that received 1.5 µCi/kg/fraction.

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Dr. Mark Berger, Actinium’s Chief Medical Officer said, "In this difficult to treat patient population, we are pleased to have observed this level of single-agent activity from Actimab-A with the benefit of minimal extramedullary toxicities. These results strongly support continued development and we have prioritized highly attractive areas that can leverage the strengths of our ARC approach. A major initiative is our Actimab-MDS trial where we have a clear pathway to a pivotal trial established with the FDA for high-risk patients with myelodysplastic syndromes. Another exciting opportunity is via combination trials with agents like venetoclax in the relapsed, refractory AML setting where the apparent synergy of mechanisms can translate to a therapeutic advantage. In addition, we are pursuing other highly-differentiated opportunities for Actimab-A as a single-agent in patients with high unmet needs where the extremely high-potency of an ARC can be used safely at low doses. An example is our novel trial in AML patients with minimal residual disease post-remission."

Overall response rate in this dosing cohort was 22% (6/27) with 3 CRps and 3 CRis. Among responding patients, 2 had adverse cytogenetics and 1 had previous MDS. This data is in addition to previously reported data from 13 patients that were treated at an original dose cohort of 2.0 µCi/kg/fraction where a 69% overall response rate was reported. The dose was lowered to 1.5 µCi/kg/fraction due to myelosuppression lasting longer than 6 weeks, which resulted in a reduction in the incidence of prolonged thrombocytopenia from 46% to 30%.

The median age of patients in this cohort of the Phase 2 trial was 75 (60 -87) with 81% of patients having ECOG performance status of 1 (13/27) or 2 (9/27). Although patients had untreated acute myeloid leukemia (AML), 52% (14/27) of patients had prior hematologic disease with 79% (11/14) having myelodysplastic syndrome (MDS), 14% (2/14) having chromic myelomonocytic leukemia (CMML) and 7% (1/14) having myelofibrosis. A majority of patients had unfavorable cytogenetics with 56% (15/27) having intermediate-risk and 26% (7/27) having high-risk cytogenetics. In addition, patients were evaluated for CD33 splicing polymorphism and responses occurred irrespective of cytogenetic risk category or splicing genotype.

Actinium also highlighted that preliminary preclinical data from its Iomab-ACT program was highlighted in the ASH (Free ASH Whitepaper) supplemental edition of blood. Actinium’s preclinical studies showed a considerable reduction in both lymphocyte and myeloid cell counts, inclusive of immune suppressive regulatory T cells and myeloid derived suppressor cells. Further, the cytoreduction by CD45-RIT was shown to induce the expression of immune homeostatic cytokines including IL-15.The abstract can be accessed he View Source

Sandesh Seth, Actinium’s Chairman and CEO said, "Given the recent and increasing competition in AML, we believe the future development pathways selected by our team strategically differentiate Actinium’s CD33 program in a manner that can maximize value creation. We have done this by focusing on an area with limited or no competition via Actimab-MDS in targeted conditioning. We have also leveraged our AWE or Antibody Radiation Conjugate technology platform to add a different modality, namely targeted radiation, to other areas of unmet or underserved needs as evidenced by our Actimab-A plus Venetoclax combinations and Actimab-A MRD trials. With our lead asset, Iomab-B progressing well in its pivotal trial, the near-pivotal Actimab-MDS program and the Iomab-ACT program for lymphodepletion prior to CAR-T, our multi-asset pipeline will enable our company to build a franchise opportunity in targeted conditioning which is almost singular in the industry."