On November 4, 2020 Protagonist Therapeutics, Inc. (NASDAQ: PTGX) reported the acceptance of one oral and four poster presentations at the American Society for Hematology (ASH) (Free ASH Whitepaper) annual meeting, taking place in a virtual format December 5-8, 2020 (Press release, Protagonist, NOV 4, 2020, View Source [SID1234569903]). The abstract data includes results as of early August 2020 from the ongoing Phase 2 study of PTG-300 in the treatment of polycythemia vera. Additional updated data from the study will be available during presentations at the conference.

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"This year’s ASH (Free ASH Whitepaper) meeting provides an opportunity for Protagonist to share detailed findings of its PTG-300 hepcidin mimetic program for polycythemia vera (PV) at a major medical conference for the first time," commented Dinesh V. Patel, Ph.D., Protagonist President and Chief Executive Officer. "We look forward to presenting updated results from our ongoing Phase 2 PTG-300 proof-of-concept PV study at the conference. We will also present an analysis of real world patient data and potential unmet need in PV, as well as promising preclinical findings with a new oral hepcidin mimetic peptide. As a non-cytoreductive treatment option based on the activity of a natural hormone, PTG-300 has truly transformative potential for PV patients and we look forward to advancing PTG-300 on the path toward regulatory approval as efficiently as possible."

Oral presentation:

1) Title: PTG-300 Eliminates the Need for Therapeutic Phlebotomy in Both Low and High-Risk Polycythemia Vera Patients (Abstract #482)
Session: 634. Myeloproliferative Syndromes: Clinical: Clinical Trials in Polycythemia Vera
Session Date: Sunday, December 6, 2020
Presentation Time: 2:45 p.m. PST
Presenter: Marina Kremyanskaya, M.D., Ph.D., Icahn School of Medicine at Mount Sinai

Poster presentations:

2) Title: Hepcidin Mimetic (PTG-300) Reverses Iron Deficiency While Controlling Hematocrit in Polycythemia Vera Patients (Abstract #1689)
Session: 102. Regulation of Iron Metabolism: Poster II
Date: Sunday, December 6, 2020
Presenter: Yelena Ginzburg, M.D., Icahn School of Medicine at Mount Sinai

3) Title: Real-World Treatments and Thrombotic Events in Polycythemia Vera Patients: A Retrospective Analysis between 2018-2019 in US Population (Abstract #2998)
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster III
Date: Monday, December 7, 2020
Presenter: Srdan Verstovsek, M.D., Ph.D., MD Anderson Cancer Center

4) Title: Mechanism of Systemic Iron Regulation and Hematocrit Control by Hepcidin Peptidomimetics in Pre-Clinical Models (Abstract #2594)
Session: 102. Regulation of Iron Metabolism: Poster III
Date: Monday, December 7, 2020
Presenter: Roopa Taranath, Ph.D., Protagonist Therapeutics

5) Title: Hepcidin Peptidomimetics – Oral Efficacy in Pre-Clinical Disease Model of Iron Overload (Abstract #2592)
Session: 102. Regulation of Iron Metabolism: Poster III
Date: Monday, December 7, 2020
Presenter: Roopa Taranath, Ph.D., Protagonist Therapeutics

Abstracts are available via the ASH (Free ASH Whitepaper) meeting website at View Source

On November 4, 2020 CTI BioPharma Corp. (Nasdaq: CTIC) reported an oral presentation supporting the Company’s pacritinib development program in graft versus host disease (GVHD) at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held virtually December 5- 8, 2020 (Press release, CTI BioPharma, NOV 4, 2020, View Source [SID1234569902]).

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The details of the presentation are as follows:

Abstract Title: Biological and Clinical Impact of JAK2/mTOR Blockade in GVHD Prevention: Preclinical and Phase I Trial Results
Session Name: Clinical Allogeneic Transplantation; Acute and Chronic GVHD, Immune Reconstitution Phase I and II Trials
Session Number: 722
Session Date: Sunday, December 6, 2020
Session Time: 9:30 a.m. – 11:00 a.m. PT
Presentation Time: 10:00 a.m. PT
Presenter: Dr. Joseph Pidala

On November 4, 2020 Avidea Technologies, Inc., a private biotechnology company developing immunotherapies through innovations in polymer-drug conjugate technologies, reported the publication of preclinical studies in Nature Immunology showing how route of vaccine administration imprints on the quality of anticancer T cell responses that affect treatment efficacy (Press release, Avidea Technologies, NOV 4, 2020, View Source [SID1234569901]). The results showed that SNAP Cancer Vaccine (SNAP CV) induced a higher proportion of stem-like (TCF1+) tumor antigen-specific CD8+ T cell responses associated with improved tumor clearance when administered intravenously (IV) as compared with more conventional routes of vaccination (for example, subcutaneous). Ahmed and colleagues (Im SJ, et al. Nature, 2016) reported that TCF1+ CD8 T cells provide a proliferative burst in response to checkpoint inhibitor (CPI) treatment. Thus, SNAP CV delivered IV provides a means to generating a key CD8 T cell population that works synergistically with CPIs.

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Avidea’s SNAP CV platform was developed for reliable, on-demand manufacturing of vaccines targeting patient-specific neoantigens by enabling precise, programmable loading of antigens and immunostimulants in self-assembling nanoparticles which target innate immune cells that prime anticancer T cell immunity. SNAP CV was previously shown to improve personalized cancer vaccine manufacturing and significantly increase neoantigen-specific CD8+ T cell responses in mice and primates when delivered subcutaneously (See Lynn GM, et al. Nature Biotechnology, 2020).

Intravenous SNAP Cancer Vaccine Generates Stem-Like (TCF1+) antigen-Specific CD8+ T cells Resulting in Improved Efficacy

"Recent discoveries in cancer immunology have demonstrated the importance of TCF1+ CD8 T cells, which have stem-like properties and show enhanced proliferation in response to checkpoint inhibitors," said Dr. Andrew Ishizuka, Avidea’s Chief Scientific Officer. "Our findings reported in Nature Immunology show how the design and route of administration of the SNAP Cancer Vaccine allows for control over the proportion of TCF1+ CD8 T cells generated in vivo."

"Many vaccines can only be given by the intramuscular or subcutaneous route. By design, SNAP CV can be administered by any route, including IV, which provides maximal flexibility to control the differentiation of anti-tumor T cells as we pursue SNAP CV monotherapy and combination immunotherapies to combat cancer," said Dr. Geoffrey Lynn, Avidea’s Chief Executive Officer. "These results provide further insight as to how SNAP CV can be best utilized to improve outcomes for cancer patients and are fueling our team’s efforts to advance this promising therapy to clinic."

Phase 1 clinical trials of SNAP CV are planned for 2021.

On November 4, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that two abstracts on the Company’s Antibody Radiation Conjugate (ARC) Iomab-B were accepted for oral presentations at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held virtually December 5-8, 2020 (Press release, Actinium Pharmaceuticals, NOV 4, 2020, View Source [SID1234569900]).

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"This is an exciting fourth quarter for the company and we are honored to have multiple oral presentations at this year’s ASH (Free ASH Whitepaper) conference. Our 3 oral presentations and one poster presentation demonstrate the clinical progress we have seen not only with Iomab-B, but our other programs including Actimab-A in combination with novel and approved therapeutic agents," stated Sandesh Seth, Actinium’s Chairman and CEO. "We look forward to presenting the Iomab-B data in further detail during the two oral presentations on the Iomab-B SIERRA study at ASH (Free ASH Whitepaper) in December. The company remains on track to report safety and feasibility data from 75% of the patients to be enrolled in SIERRA, as well as to complete the ad hoc interim analysis in the fourth quarter."

Mark Berger, Actinium’s Chief Medical officer, said, "We are encouraged that we continue to see positive ongoing results from our Phase 3 pivotal SIERRA trial in relapsed or refractory Acute Myeloid Leukemia (R/R AML) patients. In the Iomab-B Phase 3 trial we continue to see 100% engraftment in patients receiving a therapeutic dose of Iomab-B in the treatment arm whereas 83% of control arm patients failed salvage therapy, which includes the recently approved targeting agents such as venetoclax. This high failure rate demonstrates the significant need that exists in R/R AML and represents the paradigm shift we are looking to initiate with Iomab-B. The strong safety and feasibility data we have seen thus far gives us confidence that these older patients with active AML may benefit by undergoing a potentially curative bone marrow transplant which they could not receive otherwise."

Details & Highlights for Oral Presentations

Note: The two abstracts include SIERRA Phase 3 trial data available to the company from its CRO prior to August 10, 2020, the ASH (Free ASH Whitepaper) submission cutoff date. Per ASH (Free ASH Whitepaper) rules, updated data sets are permitted to be included in the live presentations.

Oral Presentation Title:

Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered

Publication Number:

193

Session Name:

721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities

Session Date:

Saturday, December 5, 2020

Presentation Time:

1:00 PM PT / 4:00 PM ET

53 patients (median age 64) were randomized to Iomab-B. 87% (46/53) received allogeneic transplant. 100% (46/46) Iomab-B transplanted patients engrafted, despite a pre-therapy median of 26% marrow blasts.
After randomization, 83% (44/53) of Conventional Care (CC) patients failed salvage therapy, including 45% (24/53) who received targeted agents. 44 CC patients were evaluated for crossover, with a median 33% marrow blasts, 59% (26/44) crossed over to Iomab-B followed by allogeneic HCT and 100% (26/26) of those patients engrafted.
Median time to neutrophil and platelet engraftment were 14 days (range 9-22) and 17 days (range 4-39) respectively, with 91% of evaluable patients achieving full donor chimerism (>95% by day 100). Neither the radiation dose delivered to the marrow (median 14.7 Gy; range, 4.6-32 Gy) nor the total administered activity (median 632 mCi; range, 354-1027 mCi) showed correlation with the time to neutrophil (p value=0.525) or platelet engraftment (p value=0.952).
Regression analyses, considering all of the variables individually, did not indicate a statistically significant correlation (p > 0.1) between days to engraftment and radiation dose delivered to the marrow.
Phase 3 SIERRA – Preliminary Results

Baseline Characteristics

Randomized to Iomab-B
(N=53)

Randomized to Conventional Care (CC)
(N=53)

Age (yrs, median, range)

64 (55-77)

65 (55-77)

Molecular & Cytogenetic Risk

Favorable: 2%
Intermediate: 33%

Adverse: 65%

Favorable: 4%

Intermediate: 30%

Adverse: 66%

% Transplanted
Intent-to-Treat Group

87% (46/53)

17% (9/53)

59% (26/44)

Results

Received Therapeutic dose of Iomab-B & Transplanted (N=46)****

Eligible to Receive Std. of Care Transplant Post-Salvage (N=9)

Evaluated for Crossover (N=44)*****

Cross-over Rate

n/a

n/a

Received Therapeutic Dose of Iomab-B (N=26)

Transplanted (N=26)

59% (26/44)

% Transplanted

100% (46/46)

17% (9/53)

100% (26/26)

BM Blast % @ baseline (median, range)

26 (4-95)

14 (5-97)

30 (6-87)

BM Blast % pre-HCT (median, range)

26 (4-95)

1 (0-3)*

32.5 (2-75)

Days to ANC Engraftment

14 (9-22)***

17 (13-83)#

14 (10-37)**

Days to Platelet Engraftment

17 (4-39)***

22 (8-35)#

19 (1-38)**

Days to HCT (Post Randomization)

30 (23-60)

66 (51-86)

65 (36-161)^

Myeloablative Dose Delivered to Bone Marrow

14.7 (4.6-32) Gv

n/a

14.4 (6.3-30) Gv

540 (313-1008) mCi

632 (354-1027) mCi

Chimerism >/= 95% by D100

91% (39/43^ Evaluable)

67% (4/6^^ Evaluable)

87% (20/23^^^ Evaluable)

100-day non-Relapse Transplant-Related Mortality

5% (2/40 Evaluable)

25% (2/8 Evaluable)

8% (2/24 Evaluable)

*1 pt with 8% BM blasts on D42 with CRp on D50, ** ANC engraftment data not available (N=3), platelet engraftment data not available (N=4); *** ANC engraftment data not available (N=4), platelet engraftment data not available (N=9), ^ 1 patient at 161 days had delayed transplant due to infection and respiratory failure, received Iomab & transplant when stable, # ANC and platelet engraftment data not available (N=2)

**** No Therapy Dose (7) due to: Declining KPS (4), Infusion Reaction (1), Unfavorable Biodistribution (1), Post-Randomization Eligibility (1); 1 Pending Treatment.

*****Ineligible for Iomab-B HCT after crossover evaluation – 13: due to Hospice Care/Progression (4), Declined/Ineligible for HCT (5), Died Pre-Crossover (4). 4 Received Dosimetry but No Therapy Dose due to Declining KPS; 2 Pending Evaluation for Crossover.

^ Did not achieve ≥95% chimerism (4); Data pending (2); Died (1); ^^ Did not achieve ≥95% chimerism (4); Data pending (1); ^^^Did not achieve ≥95% chimerism (4); Data pending (2);

Oral Presentation Title:

High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Publication Number:

135

Session Name:

721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities

Session Date:

Saturday, December 5, 2020

Presentation Time:

9:30 AM PT / 12:30 PM ET

The median dose of Iomab-B administered was 603 mCi (range 313-1027 mCi) and the median radiation dose delivered to the marrow in the Iomab-B group was 14.7 Gy (range 4.6 – 32 Gy).
All patients (n=45, median age 64) treated with a therapeutic dose of Iomab-B achieved neutrophil engraftment after a median of 14 days post-HCT (range 9-22), despite presenting with a median 26% marrow blasts prior to initiation of therapy.
No correlation between adverse events (AE) (FN, mucositis, sepsis) and administered Iomab-B activity (p=0.08), nor with dose delivered to GI tract (p=0.09) was observed. Furthermore, these AEs were not related to the dose of radiation received by the small intestine (median 2.7 Gy range 1.1-6.8 Gy) large intestine (median 2.6 Gy range 0.9-6.5 Gy), nor an average of 4 GI sites (median 2.8 Gy range 1.6-6.8 Gy).
About Iomab-B

Iomab-B via the monoclonal antibody BC8, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. BC8 is linked to the radioisotope iodine-131 and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells.

Iomab-B is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on the Company’s Phase 3 clinical trial in R/R AML can be found at sierratrial.com.

On November 4, 2020 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that twenty-one abstracts have been selected for virtual presentation, including two oral presentations, at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting taking place December 5-8, 2020 (Press release, Karyopharm, NOV 4, 2020, View Source [SID1234569899]). Key abstracts to be presented at the meeting will feature clinical data for XPOVIO (selinexor), the Company’s first in class, oral SINE compound, including: (i) updated data from the Pomalyst (pomalidomide), Kyprolis (carfilzomib) and Revlimid (lenalidomide) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; (ii) several new subgroup analyses from the pivotal Phase 3 BOSTON study evaluating once weekly XPOVIO in combination with once weekly Velcade (bortezomib) and low-dose dexamethasone against standard twice weekly Velcade in adult patients with multiple myeloma who had received one to three prior lines of therapy; and (iii) new subgroup analyses from the Phase 2b SADAL study evaluating XPOVIO in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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"Our tradition of having a strong presence at the ASH (Free ASH Whitepaper) annual meeting continues this year and we are excited to share important clinical data from a variety of our XPOVIO clinical studies," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "In total, twenty-one abstracts have been selected, including an oral presentation highlighting the all-oral regimen of XPOVIO and Pomalyst from the ongoing STOMP study. Additionally, updated data from two other arms of the STOMP study will also be presented, including the arm investigating XPOVIO and Kyprolis as well as the arm investigating XPOVIO and Revlimid. In all three arms, the response rates and safety profile continue to be encouraging. In addition, we look forward to several poster presentations describing a variety of subanalyses from the Phase 3 BOSTON study in important subgroups such as older, frail patients, patients previously treated with proteasome inhibitors, and patients with high risk cytogenetics, among others."

Karyopharm plans to host a virtual investor and analyst event to discuss the Company’s pipeline of clinical programs and highlights from the ASH (Free ASH Whitepaper) 2020 data presentations. Details for this event, including date, time, and log-in information will be announced in the coming weeks. A live webcast of the presentation will be accessed under "Events & Presentations" in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days following the event.

Details for the ASH (Free ASH Whitepaper) 2020 presentations are as follows:

XPOVIO (selinexor) – Company-Sponsored Studies – Oral Presentation – Multiple Myeloma

Title: Selinexor in combination with pomalidomide and dexamethasone (SPd) for treatment of patients with relapsed refractory multiple myeloma (RRMM).
Presenter: Christine Chen, Princess Margaret Cancer Centre
Abstract #: 726
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation; Novel Approaches for Relapsed/Refractory Myeloma and Amyloidosis
Date and Time: Monday, December 7, 2020, 1:30 p.m. to 3:00 p.m. ET
Location: Channel 10 (Virtual Meeting)

XPOVIO (selinexor) – Company-Sponsored Studies – Poster Presentations – Multiple Myeloma

Title: Selinexor in combination with carfilzomib and dexamethasone, all once weekly (SKd), for patients with relapsed/refractory multiple myeloma
Presenter: Cristina Gasparetto, Duke University Medical Center
Abstract #: 1366
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Selinexor, lenalidomide and dexamethasone (SRd) for patients with relapsed/refractory and newly diagnosed multiple myeloma
Presenter: Darrell White, Dalhousie University
Abstract #: 1393
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Effect of prior treatment with proteasome inhibitors on the efficacy and safety of once-weekly selinexor, bortezomib, and dexamethasone in comparison with twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis from the BOSTON study
Presenter: Maria Mateos, University Hospital of Salamanca
Abstract #: 2297
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Impact of prior therapies on the safety and efficacy of once-weekly selinexor, bortezomib, and dexamethasone compared with twice-weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: results from the BOSTON study
Presenter: Maria Mateos, University Hospital of Salamanca
Abstract #: 3245
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III
Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: age and frailty subgroup analyses from the phase 3 BOSTON study
Presenter: Harold Auner, Imperial College London
Abstract #: 3215
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III
Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Once weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma: high-risk cytogenetic risk planned subgroup analyses from the phase 3 BOSTON study
Presenter: Shambavi Richard, Mount Sanai Hospital
Abstract #: 1385
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Peripheral neuropathy symptoms, pain and functioning in relapsed or refractory MM patients treated with selinexor, bortezomib, and dexamethasone
Presenter: Larysa Sanchez, Icahn School of Medicine at Mount Sinai
Abstract #: 3489
Session: 906. Outcomes Research—Malignant Conditions (Myeloid Disease): Poster III
Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

XPOVIO (selinexor) – Company-Sponsored – Poster Presentations – Lymphoma

Title: Effect of age on the efficacy and safety of single agent oral selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the SADAL pivotal study
Presenter: Marie Maerevoet, Institut Jules Bordet
Abstract #: 1201
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Selinexor efficacy and safety are independent of renal function in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the pivotal phase 2b SADAL study
Presenter: Jason Westin, The University of Texas MD Anderson Cancer Center
Abstract #: 1384
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: A six-protein activity signature defines favorable response to selinexor treatment for patients with diffuse large B-cell lymphoma (DLBCL)
Presenter: Christopher Walker, Karyopharm Therapeutics
Abstract #: 2125
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

XPOVIO (selinexor) – Investigator-Sponsored – Oral Presentations – Lymphoma

Title: Inhibiting the Nuclear Exporter XPO1 and the Antiapoptotic Factor BCL2 Is Synergistic in XPO1 Mutant and Wildtype Lymphoma
Presenter: Justin Taylor, University of Miami
Abstract #: 526
Session: 605. Molecular Pharmacology, Drug Resistance—Lymphoid and Other Diseases: Molecular pharmacology and drug resistance mechanisms in lymphoproliferative disorders
Date and Time: Monday, December 7, 2020 ; 7:00 a.m. to 8:30 a.m.
Location: Channel 8 (Virtual Meeting)

XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Lymphoma

Title: Selinexor in combination with R-CHOP for frontline treatment of non-Hodgkin lymphoma: results of a phase 1b study
Presenter: Erlene Seymour, Wayne State University
Abstract #: 2109
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: A Phase I Investigator Sponsored Trial of Selinexor (KPT-330) and Rituximab, Ifosfamide, Carboplatin and Etoposide in Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas
Presenter: Sarah Rutherford, Weill Cornell Medicine
Abstract #: 2104
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: XPO1 Relieves MYC-Induced Replication Stress Limiting the Immunogenicity of DLBCL Cells
Presenter: Rossella Marullo, Weill Cornell Medicine
Abstract #: 2018
Session: 621. Lymphoma—Genetic/Epigenetic Biology: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: The Expression of Chromosome Region Maintenance Protein 1 (CRM1) in Large Cell Lymphoma
Presenter: Jithma Abeykoon, Mayo Clinic
Abstract #: 2132
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster II
Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Leukemia

Title: Frontline selinexor and chemotherapy is highly active in older adults with AML
Presenter: Timothy Pardee, Wake Forest School of Medicine
Abstract #: 633
Session: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Commercially Available Therapy, excluding Transplantation II
Date and Time: Monday, December 7, 2020, 11:45 a.m. ET
Location: Channel 12 (Virtual Meeting)

Title: Exportin-1 (XPO1) Inhibition Sequesters p53 from MDM2 and MDM4 and Is Highly Synergistic with MDM2 Inhibition in Inducing Apoptosis in Wild-Type p53 Acute Myeloid Leukemias
Presenter: Yuki Nishida, MD Anderson Cancer Center
Abstract #: 2775
Session: 603. Oncogenes and Tumor Suppressors: Poster III
Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Other

Title: CRISPR/Cas9 Chemogenetic Profiling Identifies Candidate Biomarker Genes That Modulate Sensitivity to Selinexor
Presenter: Bert Kwanten, KU Leuven
Abstract #: 965
Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster I
Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

Title: Salicylates Potentiate and Broaden CRM1 Inhibitor Anti-Tumor Activity Via S-Phase Arrest and Impaired DNA-Damage Repair
Presenter: Jithma Abeykoon, Mayo Clinic
Abstract #: 171
Session: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Novel Approaches to Overcome Resistance
Date and Time: Saturday, December 5, 2020, 12:00 p.m. ET
Location: Channel 7 (Virtual Meeting)

KPT-9274 – Investigator-Sponsored – Poster Presentations – Other

Title: Nicotinamide Phosphoribosyltransferase Inhibitors Induce Apoptosis of AML Stem Cells through Dysregulation of Lipid Metabolism
Presenter: Amit Subedi, Princess Margaret Cancer Center
Abstract #: 2777
Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III
Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET
Location: Poster Hall (Virtual Meeting)

About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and 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.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

Monitor for signs and symptoms of infection, and evaluate and treat promptly.

Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

USE IN SPECIFIC POPULATIONS

In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.