BeiGene Announces Clinical Results from Three Posters on Zanubrutinib Presented at the 24th Congress of European Hematology Association (EHA)

On June 14, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the first presentation of clinical results from the ASPEN trial, a global randomized Phase 3 open‑label trial of its investigational BTK inhibitor zanubrutinib in patients with Waldenström’s Macroglobulinemia (WM) (Press release, BeiGene, JUN 14, 2019, View Sourcenews-releases/news-release-details/beigene-announces-clinical-results-three-posters-zanubrutinib" target="_blank" title="View Sourcenews-releases/news-release-details/beigene-announces-clinical-results-three-posters-zanubrutinib" rel="nofollow">View Source [SID1234537091]). The poster presentation included clinical results from a nonrandomized exploratory cohort of patients with the MYD88WT genotype of WM. In addition, BeiGene announced updated results from the ongoing Phase 1/2 trial of patients with WM; and a pooled safety data analysis of zanubrutinib from six ongoing monotherapy studies in patients with B-cell malignancies. These data were presented in three posters at the 24thEuropean Hematology Association (EHA) (Free EHA Whitepaper) Congress, taking place June 13-16 in Amsterdam.

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"We are excited to announce new data from ongoing zanubrutinib clinical studies at EHA (Free EHA Whitepaper), including the first results of the Phase 3 ASPEN trial from a non-randomized cohort of patients who have WM with the MYD88WT genotype. For these patients, who typically have poorer prognoses with lower response rates, we recognize the real need for a highly potent and selective BTK inhibitor that can sustain BTK inhibition and reduce off-target effects. We are excited that these data have echoed what we saw in earlier trials, with an overall response rate of 81 percent and a major response rate that includes patients with a partial response or better, of 54% including 23% with a very good partial response (VGPR)," said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene. "We will continue to follow these patients to further assess outcomes. Full results from the trial are planned for presentation at a medical congress later this year."

Dr. Huang continued, "In addition, with longer follow-up from the global Phase 1/2 trial of zanubrutinib in patients with WM, we’re seeing high rates of CR/VGPR (42%) that are proving to be durable responses. Separately, the pooled safety data analysis of zanubrutinib continues to affirm its tolerability as a selective BTK inhibitor, in patients with B-cell malignancies. We believe that these data further support zanubrutinib’s potential to become a meaningful treatment option for patients with B-cell malignancies around the world."

Major Responses in Patients with MYD88 Wildtype WM Treated with Zanubrutinib

Abstract Number: PF487

The ASPEN trial, a randomized open-label, multicenter Phase 3 trial (clinicaltrials.gov Identifier: NCT03053440) of zanubrutinib vs. ibrutinib in patients with WM, has enrolled 26 patients who were centrally determined at study entry to have the MYD88WT genotype. These patients were enrolled in the non-randomized cohort and assigned to receive zanubrutinib 160mg twice daily (BID). Responses were assessed using modified IWWM-6 criteria with endpoints of combined rate of complete response (CR) and very good partial response (VGPR), overall response rate (ORR), major response rate (MRR) and safety.

This exploratory analysis included five patients with treatment-naïve (TN) disease and 21 patients with relapsed/refractory (R/R) WM.

As of February 28, 2019, the median follow-up was 12.2 months (range 2.3 – 21.7 months) and 17 patients remained on study. Results included:

The ORR was 80.8%. MRR (partial response or better) was 53.8% and the VGPR rate was 23.1%. One patient achieved a complete response by IgM criteria with normal IgM levels and negative immunofixation;

Median time to first major response (partial response or better) was 2.9 months;

Median progression‑free survival (PFS) and overall survival (OS) have not yet been reached;

Zanubrutinib tolerability was generally consistent with previous reports. Discontinuation due to adverse events (AEs) occurred in 7.7% of patients (n=2). The primary reason for discontinuation was progressive disease;

The most common AEs (in >15% pts) were diarrhea (19%), hypertension (19%), contusion (15%), constipation (15%), muscle spasm (15%), pneumonia (15%), and upper respiratory tract infection (15%);

There were no fatal AEs or atrial fibrillation/flutter events reported; and

Among adverse events of special interest for BTK inhibitors, bleeding was observed in nine patients (34.6%), hypertension was observed in five patients (19.2%), Grade 3 or 4 cytopenias were observed in four patients (15.4%), Grade 3 or 4 infections were observed in three patients (11.5%), and secondary malignancy in three patients (11.5%). Two patients had major hemorrhage (7.7%).
"Zanubrutinib is a highly potent and selective BTK inhibitor with good bioavailability that was generally well-tolerated in this exploratory cohort from the Phase 3 ASPEN trial, said Meletios A. Dimopoulos, M.D., Professor of Hematology and Medical Oncology, Chairman of the Department of Clinical Therapeutics, Rector of the National and Kapodistrian University of Athens, Greece and first author on the poster. "For the patients with wildtype MYD88 genotype, we are excited by these data that support the results we’ve seen previously from Phase 1/2 studies."

Summary of Updated Clinical Results From the Global Phase 1/2 Trial

Abstract Number PF481

This global, open-label Phase 1/2 trial (clinicaltrials.gov identifier: NCT02343120) of zanubrutinib as monotherapy in patients with B-cell malignancies, including a cohort of patients with WM, is being conducted in Australia, New Zealand, the United States, Italy, the United Kingdom and South Korea. As of September 16, 2018, 77 patients with TN (n=24) or R/R (n=53) WM without prior BTK exposure have been enrolled in the trial; the median follow-up time was 23.9 months (4.4-45.7). Seventy-three patients including 24 with TN and 49 with R/R WM, were evaluable for efficacy in this analysis, per modified IWWM-6 criteria. At the time of the data cutoff, 61 patients remained on study treatment. Updated results included:

The ORR by independent review committee (IRC) was 92% (67/73) including MRR of 82% (60/73) and CR / VGPR rate of 42% (31/73).

The estimated PFS rate at 12 and 24 months was 90% and 81%, respectively;

Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and AEs were predominantly grade 1 or 2 in severity. The most frequent AEs were upper respiratory tract infection (46%), contusion (30%), cough (20%), headache (18%) and diarrhea (17%);

Grade 3-4 AEs occurred in 51.9% of patients. Grade 3-4 AEs of any attribution reported in > 3 patients included neutropenia (10%); anemia (7.8%), basal cell carcinoma (5%) and hypertension (5%); and

With a median follow up 24 months, discontinuation due to AEs occurred in 10.4% of patients, with five fatal events.
"As we continue to follow the Phase 1/2 trial of zanubrutinib, now for more than four years, we are impressed by the tolerability and efficacy of this BTK inhibitor for patients with WM who had not received prior BTK inhibition therapy," said Judith Trotman, MBChB, FRACP, FRCPA, Clinical Professor of Medicine at Concord Repatriation General Hospital, Concord, New South Wales, Australia and first author on the poster.

Pooled Analysis of Safety Data from Monotherapy Studies of Zanubrutinib in B-cell Malignancies

Abstract Number PS1159

Safety results from six ongoing, Phase 1 and Phase 2 clinical trials of zanubrutinib monotherapy, including collectively 682 patients with non-Hodgkin’s lymphoma (NHL), WM, or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), were included in this comprehensive analysis. The majority of patients had R/R disease; almost all patients received zanubrutinib at a dose of 320mg once daily or 160mg twice daily. The median duration of zanubrutinib exposure was 13.4 months (0.1-49.7).

This analysis included an evaluation of the frequency and severity of AEs, AEs of Special Interest (AESIs), and AEs leading to death, dose reduction or treatment discontinuation (d/c).

Ninety-seven percent of patients reported at least one AE, which were primarily grade 1 or 2. The most common AEs of all grades included upper respiratory tract infection (32.4%), neutrophil count decreased (25.2%), diarrhea (19.4%), cough (19.1%), contusion (18.6%), and rash (18%). The most common grade ≥3 AEs included neutrophil count decreased (14.4%), anemia (7.6%), neutropenia (6.6%), pneumonia (4.5%), platelet count decreased (4.3%), and lung infection (4.1%). Serious AEs (SAEs) consisting primarily of infectious complications such as pneumonia/lung infection were reported in 36% of patients.

AESIs such as atrial fibrillation/flutter (1.9%), major hemorrhage (2.5%), and grade ≥3 hypertension (3.4%) were infrequent, and treatment discontinuation due to AEs was uncommon (9.1% overall, including 3.5% for whom the event(s) were treatment-related).

"Zanubrutinib was generally well-tolerated, with less than five percent discontinuation for treatment-related adverse events. These data also demonstrated low safety-related treatment failure rates at doses of zanubrutinib associated with complete and sustained BTK inhibition," commented Constantine S. Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia, and lead author of the poster presentation.

Mid-2019 Clinical Data Update Conference Call and Webcast Information:

BeiGene will host a conference call and webcast on Thursday, June 20 at 8:00 a.m. EDT. Investors and analysts are invited to join the conference call using the following dial-in information:

U.S. Toll-Free: +1 (844) 461-9930
U.S. Toll: +1 (478) 219-0535
Hong Kong Toll-Free: +852 800 279 19250
China Toll-Free: +86 800 914 686
Conference ID: 1790069

A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at View Source or View Source An archived replay will be available two hours after the event for 90 days.

About Zanubrutinib

Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

Clinical trials of zanubrutinib include a fully-enrolled, global Phase 3 clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib, currently the only approved BTK inhibitor for WM; a global Phase 3 clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); a pivotal Phase 2 trial in patients with relapsed/refractory (R/R) follicular lymphoma in combination with GAZYVA (obinutuzumab); a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/SLL; and a global Phase 1 trial. In China, BeiGene has completed two pivotal Phase 2 clinical trials of zanubrutinib in patients with MCL and CLL/SLL and the enrollment in the pivotal Phase 2 clinical trials in patients with WM.

Zanubrutinib has been granted by the U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of patients with WM, and Breakthrough Therapy designation for the treatment of adult patients with MCL who have received at least one prior therapy. The New Drug Applications (NDAs) in China for R/R MCL and R/R CLL/SLL have been accepted by the China National Medical Products Administration (NMPA) and granted priority review. BeiGene plans to submit its first NDA in the U.S. for zanubrutinib in 2019 or early 2020.

Sorrento Therapeutics to Present at the JMP Securities Life Sciences Conference in New York (NY)

On June 14, 2019 Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento") reported that senior management will be presenting in the upcoming JMP Life Sciences Conference in New York City (Press release, Sorrento Therapeutics, JUN 14, 2019, View Source [SID1234537088]).

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Sorrento Therapeutics

Speaker: Dr. Henry Ji (Chairman and CEO)

Date/Time: June 20th, 2019 at 11:30 AM

Location: The St. Regis New York, New York

Webcast: View Source

SELLAS Life Sciences Announces Pricing of $15 Million Public Offering

On June 14, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical stage biopharmaceutical company focused on the development of novel cancer immunotherapeutics for a broad range of cancer indications, reported the pricing of an underwritten public offering of (i) 26,367,200 shares of common stock together with common stock warrants (the "common warrants") to purchase 26,367,200 shares of common stock and (ii) 73,632,800 pre-funded warrants, with each pre-funded warrant exercisable for one share of common stock, together with common warrants to purchase 73,632,800 shares of common stock (Press release, Sellas Life Sciences, JUN 14, 2019, View Source [SID1234537087]). The shares of common stock (or pre-funded warrants, as applicable) and accompanying common warrants are being sold together at a combined public offering price of $0.15 per share. The common warrants will have an exercise price of $0.50 per share, will be immediately exercisable and will expire five years from the date of issuance. The common warrants also provide that if, during the period of time between the date that is 60 days after issuance and the date that is 15 months after issuance, the weighted-average price of common stock on the trading day immediately prior to the exercise date is lower than the then-applicable exercise price per share, each warrant may be exercised, at the option of the holder, on a cashless basis for one share of common stock. SELLAS has granted the underwriters an option to purchase up to an additional 15,000,000 shares of common stock and/or 15,000,000 common warrants to cover over-allotments, if any.

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The gross offering proceeds to SELLAS from the offering, before deducting the underwriting discounts and commissions and other estimated offering expenses, and excluding the exercise of any warrants, are expected to be approximately $15.0 million. The offering is expected to close on or about June 18, 2019, subject to customary closing conditions. SELLAS intends to use the net proceeds from the offering to commence a pivotal Phase 3 trial for its lead clinical candidate, galinpepimut-S ("GPS"), as a monotherapy in acute myeloid leukemia patients following second complete remission and to continue its Phase 1/2 basket type trial of GPS in combination with pembrolizumab, as well as for general corporate purposes and funding its working capital needs.

A.G.P./Alliance Global Partners is acting as sole book-running manager for the offering. Maxim Group LLC is acting as co-manager.

A registration statement on Form S-1 relating to the offering was filed with the Securities and Exchange Commission ("SEC") on May 23, 2019, amended on June 6, 2019 and June 13, 2019 and was declared effective on June 13, 2019. The offering is being made only by means of a prospectus. SELLAS’ SEC filings are available to the public from the SEC’s website at www.sec.gov. Electronic copies of the final prospectus relating to the offering may also be obtained, when available, by contacting A.G.P./Alliance Global Partners, 590 Madison Avenue, 36th Floor, New York, NY 10022 or via telephone at 212-624-2006 or email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

New Data Presented at 24th EHA Congress from Oncopeptides’ Phase 1/2 ANCHOR Trial Evaluating Melflufen in Relapsed/Refractory Multiple Myeloma (RRMM)

On June 14, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO), reported new data presented at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam, including updated interim data from the ongoing phase 1/2 ANCHOR study and data from its phase 1/2 O-12-M1 study (Press release, Oncopeptides, JUN 14, 2019, View Source [SID1234537086]).

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On 16 June 2019, interim data from Oncopeptides’ ongoing, pivotal Phase 2 HORIZON trial will also be presented as an oral presentation by Professor Paul G. Richardson, Professor of Medicine at Harvard Medical School and Clinical Program Leader, Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center Dana-Farber Cancer Institute in Boston, Massachusetts, USA.

The full posters presented at EHA (Free EHA Whitepaper) can be found on the company webpage under:

www.oncopeptides.com / Investors & media / Presentations / 2019 EHA (Free EHA Whitepaper)

Comment from CEO Jakob Lindberg
"It is very encouraging to see consistently high response rates with deepening responses over time for melflufen in combination with proteasome inhibition and anti-CD38 therapies in the ongoing ANCHOR study in patients with relapsed/refractory multiple myeloma. The progression free survival similarly looks encouraging with some patients having been on treatment for more than a year and at this point in time only one patient in each arm has experienced disease progression. Together with the emerging safety and tolerability profile, this strengthens our belief that melflufen could add value for myeloma patients also as part of combination regimens," said Jakob Lindberg, CEO of Oncopeptides. "The results from the O-12-M1 study demonstrate that melflufen can offer disease stabilization and favourable time to the next treatment. It is strategically important from a health economic perspective and supports the potential that melflufen may play an important role in the treatment of patients with RRMM."

Overall Conclusions – ANCHOR Poster Presentation

Based on interim data from the ANCHOR trial in patients with RRMM, the combination of melflufen and dexamethasone with either bortezomib or daratumumab is well tolerated.
Evolving efficacy is encouraging in both combinations, with 90% of patients still on treatment.
For patients that had completed two or more cycles of therapy the overall response rate (ORR) was 100% for the bortezomib combination and 82% for the daratumumab combination. Responses with both combinations improved with continued therapy.
No dose limiting toxicities (DLTs) have been observed across both regimens and dose levels.
Grade 3/4 adverse events (AEs) were mostly hematologic and all were clinically manageable.
Comment from Dr. Enrique Ocio
"The updated interim data from ANCHOR that is investigating the combination of melflufen and dexamethasone with either bortezomib or daratumumab in patients with relapsed/refractory multiple myeloma, show very encouraging efficacy both in terms of response rates and emerging durability of the responses. It will be exciting to continue to follow these trial results as more patients enroll in the study and continue treatment with combination regimens based on melflufen," said Dr. Enrique Ocio at Hospital Universitario Marques de Valdecilla, Santander, Spain.

About the OP-104 ANCHOR study
ANCHOR is a phase 1/2 trial where melflufen and dexamethasone is dosed in combination with either bortezomib or daratumumab. All patients must have 1-4 prior lines of therapy and be refractory (or intolerant) to an immunomodulary agent (IMiD) or a proteasome inhibitor (PI) or both. The trial is currently open for enrollment at multiple sites globally. More information can be found at: View Source;rank=4

In the bortezomib combination arm (Regimen A) patients cannot be refractory to a PI and in the daratumumab combination arm (Regimen B) patients cannot be previously exposed to any anti-CD38 therapy. Patients will be treated until documented disease progression or unacceptable toxicity. The primary objective of the phase 1 part of the study is to determine the optimal dose of melflufen, up to a maximum of 40 mg, and dexamethasone in combination with bortezomib or daratumumab. Additional patients per regimen are recruited in the phase 2 part of the trial where the primary objective is ORR.

Summary of the OP-104 ANCHOR interim data

Melflufen in combination with bortezomib – Regimen A
At the time of data cutoff, 8 May 2019, five patients had been treated with melflufen (three with 30 mg, two with 40 mg). The median age was 73 years, with a median of two prior lines (range, 2-4), and no patient had achieved CR in any previous line. All patients had relapsed / refractory disease and two of the five patients were last?line refractory (disease progression while on therapy).

The median treatment duration was 7.4 months (range, 2-11 months). Four patients were ongoing on treatment while one discontinued treatment due to disease progression after 10 months. Two patients achieved very good partial response (VGPR) and three patients achieved partial responses (PR) for an ORR of 100%.

Melflufen in combination with daratumumab – Regimen B
At the time of data cutoff, 8 May 2019, twenty-four patients had been treated with melflufen (six with 30 mg, eighteen with 40 mg). The median age was 60 years with a median of two prior lines of therapy.

The median treatment duration was 7.9 months (range, 0?11 months) and 1.2 months (range, 0?9 months) on 30 mg and 40 mg, respectively. All six patients on 30 mg and 16 of the 18 patients on 40 mg were still ongoing. Two patients discontinued treatment due to physician’s decision (one due to lack of response).

Tabell ANCHOR

Overall Conclusions – O-12-M1 Poster Presentation

Melflufen plus dexamethasone treatment results in disease stabilization in 76% of RRMM patients, which translates to a median Time To Next Treatment (TTNT) of 7.9 months (10.6 months when censoring at time of death), which compares favorably with other relevant trials.
A median OS of 20.7 months in an advanced RRMM population, suggesting that melflufen therapy is associated with a long?term benefit and allows patients to receive further treatment to control disease.
Results support previously presented data showing the promising efficacy profile of melflufen for the treatment of RRMM.
Comment from Dr. Sara Bringhen
"The data presented at EHA (Free EHA Whitepaper) from the phase 1/2 study, O-12-M1, is very important. A high proportion of patients, 76%, show disease stabilization translating into 7.9 months as median time to next treatment. The median overall survival of 20.7 months observed in this advanced RRMM patient population suggests that melflufen therapy may be associated with a long?term benefit, allowing patients to receive further treatment to control disease significantly, thereby improving patient outcomes and their quality of life," said Dr. Sara Bringhen at the Division of Hematology, University of Torino, Italy.

For further information, please contact:
Jakob Lindberg, CEO of Oncopeptides
E-mail: [email protected]
Telephone: +46 8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 70 853 72 92

The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on June 14, 2019 at 09.40 (CET).

About melflufen
Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

Karyopharm Reports New and Updated Selinexor Combination Data from the Phase 1b/2 STOMP Study at the European Hematology Association 2019 Annual Meeting

On June 14, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported three presentations highlighting new and updated data from the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study evaluating selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, and dexamethasone in combination with standard approved multiple myeloma (MM) therapies, Kyprolis (carfilzomib), Darzalex (daratumumab), or Pomalyst (pomalidomide), in patients with previously treated multiple myeloma. The data will be featured in oral and poster presentations at the European Hematology Association (EHA) (Free EHA Whitepaper) 2019 Annual Meeting taking place June 13-16, 2019 in Amsterdam (Press release, Karyopharm, JUN 14, 2019, View Source [SID1234537085]).

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"Preliminary data from the Kyprolis arm of the Phase 1b/2 STOMP study show early but encouraging clinical activity, including two patients who achieved a complete response, along with an expected and manageable tolerability profile, in patients with heavily pretreated, double-refractory Kyprolis-naïve multiple myeloma," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Additionally, the Darzalex and Pomalyst arms of the STOMP study continue to demonstrate impressive response rates, including encouraging rates of very good partial responses (VGPR), which indicate a 90% or greater reduction in a patient’s disease burden."

New Phase 1b/2 STOMP Study Data: Selinexor plus Kyprolis and Low-dose Dexamethasone (SKd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor (dosed once weekly) is being evaluated in combination with Kyprolis (56mg/m2 or 70mg/m2 once weekly) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed refractory MM who have received at least two prior therapies, which can include previous treatment with a proteasome inhibitor (PI), one or more immunomodulatory drugs (IMiDs: Revlimid, Pomalyst) or Darzalex. All patients on the study had previously received both PIs and IMiDs. The following table is a summary of the efficacy results:

Best Responses1 in Evaluable SKd Patients as of 1-May-20192
Category N ORR CR VGPR SD
All (Kyprolis-naïve) 9 7 (78%) 2 (22%) 5 (56%) 2 (22%)
Key: ORR=Overall Response Rate (CR+VGPR+PR); SD= Stable Disease
1 Responses were adjudicated according to the International Myeloma Working Group criteria
2 Based on interim unaudited data

Among the 9 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 were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (67%), fatigue (44%), hyperglycemia (44%), anorexia (33%) and vomiting (33%), and were mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included thrombocytopenia (78%), leukopenia (33%), anemia (22%) and neutropenia (22%). Dose limiting toxicities, including Grades 3 and 4 thrombocytopenia, Grade 3 pneumonia and Grade 3 vomiting, were observed in patients receiving selinexor 80mg and Kyprolis 70mg/m2 and selinexor 100mg and Kyprolis 56mg/m2. No DLTs were reported in the selinexor 80mg and Kyprolis 56mg/m2 cohort, and therefore, confirmation of the recommended Phase 2 dose (RP2D) is ongoing with this dosing regimen.

Updates on Phase 1b/2 STOMP Study: SDd and SPd

Selinexor plus Darzalex and Low-dose Dexamethasone (SDd)

In this arm of the Phase 1b/2 STOMP 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 MM who received at least three prior lines of therapy, including a PI and an IMiD, or patients with MM refractory to both a PI and an IMiD. The following table is a summary of the updated efficacy results:

Best Responses1 in Evaluable SDd Patients as of 1-May-20192
Category N3 ORR VGPR PR4
Darzalex naïve 30 22 (73%) 11 (37%) 11 (37%)
All 32 22 (69%) 11 (34%) 11 (34%)
Key: ORR=Overall Response Rate (VGPR+PR); PR= Partial Response
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 as they withdrew consent prior to disease follow up
4 Two unconfirmed PRs

Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID)-refractory disease, only one patient (3%) did not have at least a minimal response. Median progression-free survival (PFS) has not been reached. Among patients with at least a PR, the median time on treatment was 7.7 months, while the median time on study for all evaluable patients was 4.8 months. Median time to response was 1.0 month. Based on published data, the expected ORR for Darzalex therapy without selinexor in the Darzalex-naïve population is ~29%. Thus, the ORR of 73% continues to provide a basis for further evaluation of the SDd combination.

Among the 31 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 (68%), fatigue (58%), anorexia (32%), insomnia (32%), diarrhea (32%), hyponatremia (32%), and vomiting (26%), and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 treatment-related AEs were hematologic AEs and included thrombocytopenia (42%), anemia (29%), leukopenia (26%) and neutropenia (23%). No Grade 5 AEs were reported. Based on these tolerability and efficacy data, the recommended RP2D of SDd is selinexor (100mg orally, once weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, once weekly).

Selinexor plus Pomalyst and Low-dose Dexamethasone (SPd)

In this arm of the Phase 1b/2 STOMP study, oral selinexor (60mg or 80mg once weekly or 60mg or 80mg twice weekly) is being evaluated in combination with Pomalyst (2mg, 3mg or 4mg orally, once daily) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory MM who received at least two prior lines of therapy, including a PI and an IMiD, or patients with MM 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 1-May-20192
Prior Therapy Status N3 ORR VGPR PR4 Median PFS
Pomalyst-naïve and Revlimid refractory or relapsed 30 17 (57%) 7 (23%) 10 (33%) 12.2 months
Pomalyst and Revlimid refractory 10 3 (30%) - 3 (30%) 4.2 months
All 40 20 (50%) 7 (18%) 13 (33%) 10.4 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 Five patients not evaluable for response: one death unrelated to myeloma, one non-compliance with study procedures, two withdrawal of consent before disease follow up, one patient on treatment pending response evaluation
4 One unconfirmed PR

Among the 45 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 (56%), fatigue (53%) and anorexia (49%) and mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included neutropenia (56%), thrombocytopenia (31%), anemia (31%) and leukopenia (16%). There were three Grade 5 treatment-related events (febrile neutropenia, intracranial hemorrhage and pneumonia). Determination of the RP2D is still ongoing.

Details for the EHA (Free EHA Whitepaper) 2019 STOMP presentations are as follows:

Oral Presentation

Title: Safety and Efficacy of combination of Selinexor, Daratumumab, and Dexamethasone (SDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs
Lead author:Cristina Gasparetto, Duke University Cancer Center
Abstract #: S1606
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:Sunday, June 16, 2019; 09:00 – 09:15 CEST
Location: Auditorium

Poster Presentations

Title: Selinexor, Pomalidomide, and Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
Lead author:Christina Chen, Princess Margaret Cancer Center
Abstract #: PF587
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:Friday, June 14, 2019; 17:30 – 19:00 CEST
Location: Poster Area

Title:A Phase 1b/2 Study of Selinexor, Carfilzomib, and Dexamethasone (SKd) in Relapsed/ Refractory Multiple Myeloma (RRMM)
Lead author:Cristina Gasparetto, Duke University Cancer Center
Abstract #: PS1414
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:Saturday, June 15, 2019; 17:30 – 19:00 CEST
Location: Poster Area

Additional selinexor presentations at EHA (Free EHA Whitepaper) 2019 are as follows:

Title:A Phase 2 Study of Selinexor Plus Cytarabine and Idarubicin in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
Lead author:Walter Fiedler, Hubertus Wald University Cancer Center Hamburg
Abstract #: S880
Session: Acute myeloid leukemia – Clinical
Date and Time:Saturday, June 15, 2019; 17:00 – 17:15 CEST
Location: Elicium 2

Title: A Randomized, Open-Label, Phase II Study of Selinexor Versus Physician’s Choice (PC) In Older Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)
Lead author:Kendra Sweet, Moffitt Cancer Center
Abstract #: PF261
Session: Acute myeloid leukemia – Clinical
Date and Time:Friday, June 14, 2019; 17:30 – 19:00 CEST
Location: Poster Area

Note: As reported previously by Karyopharm in 2017, this study did not meet its pre-specified primary endpoint.

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. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. 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) seeking accelerated approval 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 based on data from the STORM study. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. 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 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.