On August 8, 2018 CBT Pharmaceuticals (CBT), a U.S. and China-based innovative biopharmaceutical company committed to becoming a leader in the discovery and development of oncology combination therapies, reported the receipt of ethics approval from the Bellberry Human Research Ethics Committee (HREC) in Australia for its planned APOLLO-1 clinical trial (Press release, CBT Pharmaceuticals, AUG 8, 2018, View Source [SID1234528576]). HREC is an independent ethics review board compliant with strict national Health and Medical Research Council (NHMRC) guidelines for clinical trials.

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"Ethics approval is an essential element of the process to initiate a clinical trial in Australia as we prepare to launch our first combination study with our proprietary c-Met inhibitor and anti PD-1 immunotherapies," stated Sanjeev Redkar, PhD, President and Chief Executive Officer. "We are thrilled to partner with the world-leading oncologists and hepatologists in Australia who are highly experienced clinical trial investigators and share our commitment to the development of new combination approaches to treat cancer patients."

APOLLO-1 is a Phase 1/2 open label, multi-center dose escalation and expansion study of combination immunotherapy in locally advanced or metastatic disease: CBT-101 (c-Met inhibitor) with CBT-501 (anti-PD-1) in hepatocellular carcinoma (HCC), or CBT-101 and nivolumab in renal cell carcinoma (RCC). CBT-101 is CBT’s c-Met inhibitor targeting the epithelial to mesenchymal transition (EMT) pathway, and CBT-501 is CBT’s IgG4 humanized monoclonal antibody against the Programmable Death-1 (PD-1) membrane receptor on immune cells. Nivolumab (OPDIVO; Bristol-Myers Squibb Company) is approved for advanced kidney cancer. CBT-101 will be administered concomitantly with the PD-1 cancer immunotherapy.

"Our c-Met inhibitor may improve responses to cancer immunotherapy in settings beyond c-MET-dependent tumors by eliminating resistance in the tumor microenvironment, reactivating T-cells to kill the tumor, and sustaining that T-cell response. We look forward to initiating the trial in the next few weeks," added Tillman Pearce, MD, Chief Medical Officer.

About CBT-501 (genolimzumab Injection)

CBT-501 is a novel IgG4 humanized monoclonal antibody against the Programmable Death-1 (PD-1) membrane receptor on immune cells. It has a comparable efficacy profile in in vitro and in vivo studies to the marketed anti-PD-1 antibodies, nivolumab and pembrolizumab, and has a favorable profile with very low antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) activity. In China, CBT-501 is referred to as GB226 where it is being developed by CBT partner Genor BioPharma Co. Ltd. Visit clinicaltrials.gov for additional information on the ongoing clinical trials: NCT03053466, NCT03374007, and NCT03502629.

CBT-101 Oral Capsule

CBT-101 is a novel, small molecule drug that targets the epithelial to mesenchymal transition (EMT) pathway that is dysregulated in several tumors. It is a specific inhibitor of the c-Met receptor. CBT-101 has demonstrated tumor inhibitory effect in a variety of human primary c-Met amplified gastric, hepatic, pancreatic and lung cancer xenograft animal models with c-Met fusions, mutations or amplifications. In China, CBT-101 is referred to as PLB1001 where it is being developed by CBT partner Beijing Pearl Biotechnology Co. Ltd. Visit clinicaltrials.gov for additional information on the ongoing clinical trials: NCT03175224, NCT02896231, and NCT02978261.

On August 8, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) and a Type II Variation to the European Medicines Agency (EMA) seeking approval of a split dosing regimen for DARZALEX (daratumumab) (Press release, Johnson & Johnson, AUG 8, 2018, View Source [SID1234528659]). The applications seek to update the Prescribing Information and Summary of Product Characteristics to provide health care professionals with the option to split the first infusion of DARZALEX over two consecutive days. The submissions are supported by data from the Phase 1b MMY1001 clinical trial, which demonstrated DARZALEX pharmacokinetics (PK) concentrations were comparable regardless of whether the first dose was administered as a split infusion or single first infusion in patients with multiple myeloma.

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1 The safety profile of DARZALEX was comparable when administered initially as a split or single dose.1
"We are committed to exploring options that may improve the administration profile of DARZALEX and the overall
treatment experience for patients and physicians," said Craig Tendler, MD, Vice President, Clinical Development
and Global Medical Affairs, Janssen Research & Development, LLC. "We look forward to reviewing the data in
support of these applications with regulators and hope to make a DARZALEX split-dose option available to
patients and health care professionals to provide additional flexibility in administration of the initial infusion."

The regulatory submission is based on data from the global, multi-arm Phase 1b MMY1001 study in multiple
myeloma, which evaluated DARZALEX in combination with various treatment regimens.
1 Splitting the first dose of
DARZALEX effectively reduced the duration of the first infusion and resulted in a similar rate and pattern of
infusion reactions.
1 Data from MMY1001 demonstrated that DARZALEX concentrations were comparable after
administration of the first 16 mg/kg dose regardless of whether it was administered as a split infusion or single first
infusion in all approved indications.
1 No new safety events were observed with split dosing.
1
In the U.S., DARZALEX first received FDA approval in November 2015 as a monotherapy for patients with
multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and
an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.2 DARZALEX
received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or
bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least
one prior therapy.3
In June 2017, DARZALEX received approval in combination with pomalidomide and
dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies,
including lenalidomide and a PI.4 Most recently, in May 2018, DARZALEX received approval in combination with
bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who
are ineligible for autologous stem cell transplant (ASCT), making it the first monoclonal antibody approved for
newly diagnosed patients with this disease.5
In the European Union (EU), DARZALEX first received European Commission approval in May 2016 as a
monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy
included a PI and an immunomodulatory agent, and who have demonstrated disease progression on the last
therapy.
6 DARZALEX received an additional approval in April 2017 for use in combination with lenalidomide and
dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who
have received at least one prior therapy.
6 Finally, in July 2018, DARZALEX received a positive opinion from the
Committee for Medicinal Products for Human Use (CHMP) recommending broadening the existing marketing
authorization for use in combination with bortezomib, melphalan and prednisone for the treatment of adult patients
with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a global license and development agreement,
which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX.
7 For the full
U.S. Prescribing Information, please visit www.DARZALEX.com. For the full EU Summary of Product
Characteristics, please click here.
About DARZALEX (daratumumab) Injection, for Intravenous Infusion
DARZALEX (daratumumab) injection for intravenous use is the first CD38-directed antibody approved anywhere
in the world.5 CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of
3
disease stage.8 DARZALEX is believed to induce tumor cell death through multiple immune-mediated
mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated
cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which
a series of molecular steps in a cell lead to its death.5 Subsets of myeloid derived suppressor cells (MDSCs),
CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by DARZALEX.
5 DARZALEX is
being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple
myeloma, such as in frontline and relapsed settings.
9,10,11,12,13,14,15,16 Additional studies are ongoing or planned to
assess its potential in other malignant and pre-malignant hematologic diseases in which CD38 is expressed, such
as smoldering myeloma, as well as in solid tumors.
17,18,19 DARZALEX is the first and only CD38-directed antibody
to receive regulatory approval to treat multiple myeloma.5
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the
bone marrow.20,21 Refractory cancer occurs when a patient’s disease is resistant to treatment or in the case of
multiple myeloma, patients progress within 60 days of their last therapy.22,23 Relapsed cancer means the disease
has returned after a period of initial, partial or complete remission.24
In 2018, it is estimated that 30,700 people will
be diagnosed, and 12,770 will die from the disease in the United States.25 Additionally, there were 40,570 new
cases of multiple myeloma in Europe in 2015.26 The most recent five-year survival data for 2000-2007 show that
across Europe, up to half of newly diagnosed patients do not reach five-year survival.27 While some patients with
multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms, which can include bone
fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.28
IMPORTANT SAFETY INFORMATION5
CONTRAINDICATIONS
DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to
daratumumab or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Infusion Reactions – DARZALEX can cause severe and/or serious infusion reactions, including
anaphylactic reactions. In clinical trials, approximately half of all patients experienced an infusion reaction.
Most infusion reactions occurred during the first infusion and were grade 1-2. Infusion reactions can also occur
with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an
infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up
to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea,
hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory
symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less
4
common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients
during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management
as needed. Permanently discontinue therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction
occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the
infusion rate when re-starting the infusion.
To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following
DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require
additional post-infusion medications to manage respiratory complications. Consider prescribing short- and
long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary
disease.
Interference with Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and
results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive
indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion.
Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The
determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of
this interference with serological testing and inform blood banks that a patient has received
DARZALEX. Type and screen patients prior to starting DARZALEX.
Neutropenia – DARZALEX may increase neutropenia induced by background therapy. Monitor
complete blood cell counts periodically during treatment according to manufacturer’s prescribing
information for background therapies. Monitor patients with neutropenia for signs of infection.
DARZALEX dose delay may be required to allow recovery of neutrophils. No dose reduction of
DARZALEX is recommended. Consider supportive care with growth factors.
Thrombocytopenia – DARZALEX may increase thrombocytopenia induced by background therapy.
Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing
information for background therapies. DARZALEX dose delay may be required to allow recovery of
platelets. No dose reduction of DARZALEX is recommended. Consider supportive care with transfusions.
Interference with Determination of Complete Response – Daratumumab is a human IgG kappa
monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and
immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can
impact the determination of complete response and of disease progression in some patients with IgG kappa
5
myeloma protein.
Adverse Reactions – The most frequently reported adverse reactions (incidence ≥20%) in clinical trials were:
infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle
spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral
sensory neuropathy and upper respiratory tract infection.
In patients who received DARZALEX in combination with bortezomib, melphalan, and prednisone (DVMP), the
most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory tract infection (48%), infusion
reactions (28%), and peripheral edema (21%). Serious adverse reactions (≥2% compared to the VMP arm) were
pneumonia (11%), upper respiratory tract infection (5%), and pulmonary edema (2%). Treatment-emergent Grade
3-4 hematology laboratory abnormalities ≥20% were lymphopenia (58%), neutropenia (44%), and
thrombocytopenia (38%).
In patients who received DARZALEX in combination with lenalidomide and dexamethasone, the most
frequently reported adverse reactions (incidence ≥20%) were: upper respiratory tract infection (65%), infusion
reactions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea
(21%) and pyrexia (20%). The overall incidence of serious adverse reactions was 49%. Serious adverse
reactions (≥2% compared to Rd) were pneumonia (12%), upper respiratory tract infection (7%), influenza
(3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were
neutropenia (53%) and lymphopenia (52%).
In patients who received DARZALEX in combination with bortezomib and dexamethasone, the most
frequently reported adverse reactions (incidence ≥20%) were: peripheral sensory neuropathy (47%), infusion
reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema
(22%), and dyspnea (21%). The overall incidence of serious adverse reactions was 42%. Serious adverse
reactions (≥2% compared to Vd) were upper respiratory tract infection (5%), diarrhea (2%) and atrial fibrillation
(2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were lymphopenia (48%)
and thrombocytopenia (47%).
In patients who received DARZALEX in combination with pomalidomide and dexamethasone, the most
frequent adverse reactions (>20%) were fatigue (50%), infusion reactions (50%), upper respiratory tract infection
(50%), cough (43%), diarrhea (38%), constipation (33%), dyspnea (33%), nausea (30%), muscle spasms (26%),
back pain (25%), pyrexia (25%), insomnia (23%), arthralgia (22%), dizziness (21%), and vomiting (21%). The
overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients
included pneumonia (7%). Treatment-emergent hematology Grade 3-4 laboratory abnormalities ≥20% were
anemia (30%), neutropenia (82%), and lymphopenia (71%).
6
In patients who received DARZALEX as monotherapy, the most frequently reported adverse reactions
(incidence ≥20%) were: infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia
(21%), cough (21%), and upper respiratory tract infection (20%). The overall incidence of serious adverse
reactions was 33%. The most frequent serious adverse reactions were pneumonia (6%), general physical
health deterioration (3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory
abnormalities ≥20% were lymphopenia (40%) and neutropenia (20%).
DRUG INTERACTIONS
Effect of Other Drugs on Daratumumab: The coadministration of lenalidomide, pomalidomide or bortezomib
with DARZALEX did not affect the pharmacokinetics of daratumumab.
Effect of Daratumumab on Other Drugs: The coadministration of DARZALEX with bortezomib or
pomalidomide did not affect the pharmacokinetics of bortezomib or pomalidomide.

On August 7, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the second quarter 2018 and provided an overview of recent accomplishments and clinical development plans for selinexor, its lead, novel, oral SINE compound and its other pipeline programs (Press release, Karyopharm, AUG 7, 2018, View Source [SID1234528491]).

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"We have made tremendous progress toward advancing our lead drug candidate, selinexor, as we strive to improve the lives of patients with myeloma and other forms of cancer. Most notably, we have now completed the submission of our first New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for selinexor as a potential new treatment for patients with penta-refractory myeloma," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "The positive results from the Phase 2b STORM study announced during the quarter demonstrated that treatment with selinexor may result in an important clinical benefit in this patient population and we look forward to working with the FDA during their review of the application. We are making excellent progress in advancing commercial preparation for the potential launch of selinexor in the U.S., as well as preparing a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA), which we expect to submit in early 2019, with a request for conditional approval, also in penta-refractory myeloma. Finally, while completing our first-ever NDA submission is clearly a landmark event for Karyopharm, we remain committed to fulfilling the full potential of selinexor as we advance our clinical strategy in earlier lines of treatment in myeloma and in additional tumor types."

Second Quarter 2018 and Recent Events

Selinexor in Multiple Myeloma

Submitted NDA in Penta-Refractory Myeloma. Karyopharm completed its submission of an NDA to the FDA seeking accelerated approval for selinexor, its lead, novel, oral SINE compound, as a new treatment for patients with penta-refractory multiple 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 (lenalidomide) and Pomalyst (pomalidomide), and the anti-CD38 monoclonal antibody Darzalex (daratumumab) as well as alkylating agents, and their disease is refractory to at least one PI, at least one IMiD, Darzalex and their most recent therapy. The Company also plans to submit an MAA to the EMA in early 2019 with a request for conditional approval in the same indication.

Reported Positive Top-line Data from the Phase 2b STORM Study in Patients with Penta-Refractory Myeloma. Karyopharm reported positive top-line results from Part 2 of the Phase 2b STORM study evaluating selinexor plus low dose dexamethasone (Sd) in patients with penta-refractory multiple myeloma. The STORM study’s primary endpoint of overall response rate (ORR) was 25.4%, which included two stringent complete responses (sCRs) and 29 partial or very good partial responses. The two sCRs were negative for minimal residual disease, one at 1:10-6 and one at 1:10-4, which is particularly significant in this penta-refractory population. The median duration of response, a key secondary objective, was 4.4 months. Across the relevant patient population, side effects of oral selinexor were generally predictable and often managed with dose adjustments or supportive care. Safety results were consistent with those previously reported from Part 1 of this study and from other selinexor studies and no new safety signals were identified. Karyopharm plans to submit detailed STORM study results for presentation at an upcoming medical oncology meeting.

Presented Updated Data from the Phase 1b/2 STOMP Study at the European Hematology Association (EHA) (Free EHA Whitepaper) 2018 Annual Meeting. At EHA (Free EHA Whitepaper) 2018, Karyopharm presented three posters with updated data from STOMP evaluating selinexor and dexamethasone in combination with standard approved therapies, Velcade (SVd), Pomalyst (SPd) or Darzalex (SDd), in patients with previously treated multiple myeloma. The SVd arm demonstrated progression-free survival (PFS) of 17.8 months, an ORR of 83% in the same patient population eligible for the pivotal Phase 3 BOSTON study. The SDd arm demonstrated an ORR of 82% in patients with heavily pretreated Darzalex-naïve disease. The all oral SPd arm demonstrated an ORR of 55% in patients with Pomalyst-naïve and Revlimid-relapsed or -refractory disease, with a PFS of 11.6 months. Adverse events across all three arms were consistent with those reported previously with selinexor and the combination therapies, with no new safety signals specific to the combinations identified. These results suggest that selinexor can be combined with other anti-myeloma agents and induce durable responses in patients with previously treated MM.
Initiated New STOMP Arm Evaluating All Oral Regimen of Selinexor, Revlimid and Dexamethasone (SRd) in Patients with Newly Diagnosed Myeloma. Based on the positive STOMP results reported to date evaluating SRd in patients with relapsed myeloma, the Company initiated a new, all oral STOMP arm to investigate the combination of SRd in the front-line setting. Given the observed synergistic activity of selinexor with standard approved multiple myeloma therapies, Karyopharm believes oral selinexor has the potential to be a future backbone therapy in multiple myeloma.
Pivotal Phase 3 BOSTON Study in Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is underway and enrolling patients in 14 countries. BOSTON is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and low-dose dexamethasone (SVd), compared to standard twice weekly Velcade and low-dose dexamethasone (Vd) in patients with multiple myeloma who have had one to three prior lines of therapy. The primary endpoints of the study are PFS and ORR. Data from the BOSTON study, if positive, would be used to support regulatory submissions to the FDA and EMA requesting full approvals for use of selinexor in second line multiple myeloma, following the Company’s requests for accelerated and conditional approvals, respectively, using data from the Phase 2b STORM study. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and expects to complete enrollment by the end of 2018, with top-line data anticipated in 2019.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Ongoing Phase 2b SADAL Study in DLBCL. Karyopharm is also investigating oral selinexor as a single-agent for the treatment of patients with relapsed or refractory DLBCL who are not eligible for stem cell transplantation. The SADAL study is expected to enroll up to a total of 130 patients in the single-arm cohort evaluating single-agent selinexor dosed 60mg twice weekly in patients who received two to five lines of prior therapy. Karyopharm plans to report top-line results by the end of 2018. Assuming the results from the SADAL study are positive, Karyopharm plans to submit an NDA to the FDA with a request for accelerated approval, and an MAA to the EMA with a request for conditional approval, for oral selinexor in this relapsed/refractory DLBCL patient population.
Selinexor in Solid Tumors

Presented Data from the Phase 2 Portion of the Phase 2/3 SEAL Study in Liposarcoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting. At ASCO (Free ASCO Whitepaper) 2018, Karyopharm presented positive results from the successful Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. For the primary endpoint of PFS, oral selinexor showed superiority over placebo, achieving a median PFS of 5.5 months, compared to 2.7 months for placebo with a hazard ratio (HR) of 0.67, representing a 33% reduction in the risk of progression or death. Across the relevant patient population, side effects of oral selinexor were generally predictable and often managed with dose adjustments or supportive care, with the most frequent events being nausea, fatigue, anorexia and weight loss, with low levels of Grade 3/4 cytopenias, and no new or unexpected safety signals identified. The Phase 3 portion of the SEAL study is underway and, assuming a positive outcome on the primary end point of PFS, the Company intends to use the data from the SEAL study to support an NDA and an MAA submission requesting full approval for oral selinexor for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated by the end of 2019.
Ongoing Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer Underway. A randomized Phase 2/3 study of selinexor versus placebo as maintenance therapy in patients with one or two prior platinum-based treatments for advanced endometrial cancer lead by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, is currently ongoing. In the U.S., endometrial cancer is the most common gynecological cancer with approximately 58,000 cases expected to be diagnosed and an estimated 10,000 women expected to die from this cancer in 20181, revealing a meaningful patient population in need of novel therapies.
Corporate Updates

Anand Varadan Appointed Chief Commercial Officer. Karyopharm announced the appointment of Anand Varadan as Executive Vice President, Chief Commercial Officer. Mr. Varadan brings over 25 years of commercial operations and strategy experience with a proven track record of building and leading commercial and cross-functional teams and successfully launching and marketing new therapeutics at publicly-traded, healthcare-focused companies. Mr. Varadan leads the Company’s commercial strategy and operations, including for the launch of selinexor.

Ian Karp Appointed Vice President, Investor and Public Relations. The Company also appointed Ian Karp as Vice President, Investor and Public Relations. Mr. Karp brings over 20 years of investor relations, corporate development, and commercial experience and has successfully led global teams in achieving key corporate communications objectives, including in the areas of oncology and orphan diseases. Mr. Karp leads all of the Company’s corporate communications activities, including corporate visibility, financial communications, and media and investor relations.
Exclusive License Agreement Executed with Antengene to Develop and Commercialize Selinexor, Eltanexor, Verdinexor and KPT-9274 in China and Other Regions in Asia. The agreement includes the development of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in China and Macau. The agreement also includes the development and commercialization of KPT-9274 in all human oncology indications and verdinexor in human non-oncology indications in mainland China, Macau, Taiwan, Hong Kong, South Korea, and the ASEAN countries. The transaction carries a total deal value of up to $162 million, plus royalties.
Second Quarter Ended June 30, 2018 Financial Results

Cash, cash equivalents and investments as of June 30, 2018, including restricted cash, totaled $250.5 million, compared to $176.4 million as of December 31, 2017.

On May 7, 2018, Karyopharm completed an underwritten public offering of 10,525,424 shares of its common stock at a price to the public of $14.75 per share, resulting in net proceeds of approximately $145.7 million after deducting the underwriting discounts and commissions and other offering expenses.

For the quarter ended June 30, 2018, Karyopharm recognized $19.9 million in revenue, compared to a small amount of grant revenue for the three months ended June 30, 2017. The increase in revenue was primarily the result of recognizing $19.7 million of revenue related to fulfilling an obligation under our license agreement with Ono Pharmaceutical Co., LTD. The cash related to this revenue was received as part of the upfront payment received from Ono in October 2017.

For the quarter ended June 30, 2018, research and development expense was $44.7 million compared to $23.1 million for the quarter ended June 30, 2017. For the quarter ended June 30, 2018, general and administrative expense was $9.5 million compared to $6.6 million for the quarter ended June 30, 2017.

Karyopharm reported a net loss of $33.7 million, or $0.60 per share, for the quarter ended June 30, 2018, compared to a net loss of $29.4 million, or $0.64 per share, for the quarter ended June 30, 2017. Net loss includes stock-based compensation expense of $4.4 million and $5.1 million for the quarters ended June 30, 2018 and June 30, 2017, respectively.

Financial Outlook

Karyopharm expects its operating cash burn, including research and development and general and administrative expenses, for the year ending December 31, 2018 to be in the range of $175 to 185 million. Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations for at least the next twelve months. These plans include the continued clinical development of selinexor in the Company’s lead indications with a focus on preparing the commercial infrastructure and hiring a sales force for the potential launch of selinexor in the U.S. Additional key activities expected in 2018 include preparing for a potential MAA submission to the EMA requesting conditional approval for selinexor in multiple myeloma, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like overall response rate (ORR). Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma, accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies. FDA’s Fast Track designation is available to therapeutics treating an unmet medical need in a serious condition; the Company has received Fast Track designation from the FDA specifically for the population treated in the STORM trial. In light of this recognition that the STORM patient population represents an unmet medical need and the positive top-line data reported in April 2018, the Company believes that the STORM study should support its request to the FDA for accelerated approval.

Conference Call Information

Karyopharm will host a conference call today, Tuesday, August 7, 2018, at 8:30 a.m. Eastern Time, to discuss the second quarter 2018 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 3084449. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

On August 7, 2018 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on unmet medical needs in inflammation, reported operating results for the second quarter ended June 30, 2018 and provided pipeline updates (Press release, AnaptysBio, AUG 7, 2018, View Source [SID1234528509]).

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"We made significant advances during the second quarter of 2018 in the clinical development of our first-in-class wholly-owned antibody therapeutics for patients with severe inflammatory conditions," said Hamza Suria, president and chief executive officer of AnaptysBio. "We are excited to advance the clinical development of etokimab in large atopic disease markets, including our ongoing Phase 2b ATLAS trial in moderate-to-severe atopic dermatitis, our ongoing Phase 2a trial in severe eosinophilic asthma and our upcoming Phase 2 ECLIPSE trial in adult chronic rhinosinusitis with nasal polyps. Development of ANB019 in orphan diseases has been initiated with our Phase 2 GALLOP trial in generalized pustular psoriasis and upcoming Phase 2 POPLAR trial in palmoplantar pustulosis. We look forward to the five clinical efficacy readouts anticipated from our etokimab and ANB019 programs by the end of 2019, starting with our upcoming etokimab Phase 2a top-line data in eosinophilic asthma during the third quarter of 2018, as key milestones in our mission to bring novel treatments to patients with severe inflammatory diseases."

Etokimab (ANB020 Anti-IL-33 Program)

• In July 2018, etokimab (pronounced ee-toh-key-mab) was adopted as the nonproprietary name by the United States Adopted Names (USAN) Council, in consultation with the World Health Organization (WHO) International Nonproprietary Names Expert Committee, for AnaptysBio’s anti-IL-33 antibody drug candidate previously referred to as ANB020.

• In May 2018, updated data from the company’s Phase 2a trial of etokimab, AnaptysBio’s wholly-owned anti-IL-33 antibody program, in adult patients with moderate-to-severe atopic dermatitis were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2018 in Munich by the principal investigator of the trial, Dr. Graham Ogg, professor of dermatology at Oxford University in Oxford, England. Key observations presented by Dr. Ogg during the aforementioned presentation included:

Biomarker data demonstrated that reduction of circulating blood eosinophil was consistent with clinical efficacy measures in this Phase 2a trial, with a maximum reduction of 40 percent at day 29 after a single dose of etokimab relative to baseline, which is aligned with genotypic studies that associate lower eosinophil counts with human IL-33 loss-of-function mutations. In addition, clinical efficacy data in this Phase 2a trial were consistent with an ex vivo pharmacodynamic assay measuring IL-33 mediated interferon-gamma release, where 98 percent inhibition was observed within 72 hours following etokimab administration and 86 percent inhibition was sustained at day 57 post-ANB020 administration, which is consistent with the pharmacodynamic activity observed using the same assay in a prior Phase 1 trial of etokimab in healthy volunteers.
A single dose of etokimab resulted in achievement of EASI-50 by all 12 patients enrolled in this trial on or before day 57 post-etokimab administration. Rapid clinical response was observed by day 15 post-etokimab administration and day 29 results exceeded the primary efficacy objective of the trial with 10 of 12 patients (83%) achieving EASI-50, of which four patients (33%) also achieved EASI-75. EASI-50 results were sustained through day 140 following single dose administration of etokimab, five of 12 patients (42%) achieved EASI-50, of which three patients (25%) also achieved EASI-75. Other atopic dermatitis efficacy endpoints, including the five-point Investigator’s Global Assessment (IGA) scale, the SCORing Atopic Dermatitis (SCORAD) scale, Dermatology Life Quality Index (DLQI) and the five-dimensional pruritus scale, demonstrated rapid and sustained single dose etokimab efficacy results in a similar manner to the aforementioned EASI results.
Etokimab was generally well-tolerated by all patients and no drug-related safety signals were observed. The most frequent adverse events reported were dizziness in 17 percent of patients post-placebo and headache in 25 percent of patients post-etokimab administration. A single serious adverse event of depression was reported on day 140 post-etokimab administration, which was consistent with the patient’s pre-trial history of depression and was deemed not drug-related.
• The company is enrolling a Phase 2b randomized, double-blinded, placebo-controlled, multi-dose study in 300 adult patients with moderate-to-severe atopic dermatitis, also referred to as the ATLAS clinical trial, to assess different dose levels and dosing frequencies of subcutaneously-administered etokimab for a 16-week treatment period followed by an eight-week follow-up period, with data expected in the second half of 2019. Sixty patients are being randomized into each of the five arms in the ATLAS trial where dosing will occur as follows: (i) initial 600mg loading dose followed by 300mg monthly doses of etokimab, (ii) initial 300mg loading dose followed by 150mg monthly doses of etokimab, (iii) initial 300mg loading dose followed by 150mg doses of etokimab every eight weeks, (iv) monthly 20mg doses of etokimab and (v) monthly doses of placebo.

• AnaptysBio expects to report top-line efficacy and safety data, including improvement in Forced Expiratory Volume in One Second (FEV1), from its ongoing double-blinded, placebo-controlled severe eosinophilic asthma trial Phase 2a trial, where approximately 24 adult severe eosinophilic asthma patients are treated with a 300mg intravenous single dose of etokimab versus placebo, each in combination with inhaled corticosteroids and long-acting beta agonists as background therapy, in the third quarter of 2018.

• The Company has expanded development of etokimab into adult chronic rhinosinusitis with nasal polyps (CRSwNP), which is a debilitating atopic disorder associated with elevated IL-33 pathway signaling, affecting approximately 1.3 million adults in the U.S., and AnaptysBio estimates approximately 400,000 of these patients are inadequately controlled with standard-of-care. The Company plans to initiate a randomized, placebo-controlled Phase 2 trial, also referred to as the ECLIPSE trial, in approximately 100 adult CRSwNP patients treated with two different multi-dosing frequencies of subcutaneously-administered etokimab or placebo, each in combination with mometasone furoate nasal spray as background therapy, for a treatment period of 16 weeks followed by an eight-week follow-up period. The Company plans to initiate the ECLIPSE trial by the end of 2018, and anticipates top-line data will be available in the second half of 2019.

• As a result of market assessment regarding the adoption of the peanut oral food challenge in future commercial usage of etokimab in peanut allergy patients, AnaptysBio has decided to deprioritize further company-sponsored clinical development of etokimab in moderate-to-severe baseline adult peanut allergy patients. At this time, AnaptysBio does not intend to utilize its clinical development resources to pursue a Phase 2b clinical trial of etokimab in peanut allergy, however the Company may pursue potential investigator-sponsored trials related to this indication.

ANB019 (Anti-IL-36 Receptor Program)

• Data from the company’s Phase 1 healthy volunteer trial of ANB019, its wholly-owned anti-interleukin-36 receptor, or IL-36R therapeutic antibody, were presented during May in a poster session at the EAACI Congress 2018 in Munich. In the double-blind, placebo-controlled healthy volunteer Phase 1 trial, 36 subjects were administered a single subcutaneous or intravenous dose of ANB019 ranging between 10 mg and 750 mg, 18 subjects were administered multiple ascending doses of ANB019 intravenously ranging between 40 mg and 300 mg weekly for four consecutive weeks and 18 subjects were dosed with placebo. ANB019 was well-tolerated by all subjects and no dose-limiting toxicities were observed. The most frequent treatment-emergent adverse events observed in the single ascending dose cohorts were upper respiratory tract infections in 10 of 36 (28%) subjects dosed with ANB019 versus six of 12 (50%) subjects dosed with placebo, and headache in 10 of 36 (28%) subjects dosed with ANB019 versus three of 12 (25%) subjects dosed with placebo. In the multiple ascending dose cohorts, the most frequent treatment-emerging adverse events observed were headache in seven of 18 (39%) subjects dosed with ANB019 versus one of six (17%) subjects dosed with placebo. No serious adverse events were reported among any subjects in the trial. The in vivo half-life of ANB019 was approximately 28 days for both subcutaneous and intravenous routes of administration, with bioavailability of approximately 90 percent. A single dose of ANB019 at certain dose levels was able to completely suppress IL-36 cytokine function for 85 days, as measured by IL-36 cytokine-mediated release of IL-8 using an ex vivo pharmacodynamic assay. The favorable safety, pharmacokinetics and pharmacodynamic properties of ANB019 demonstrated by this Phase 1 trial support advancement of ANB019 into Phase 2 studies for GPP and PPP.

• AnaptysBio has initiated a 10-patient open-label Phase 2 trial of ANB019 in GPP, also known as the GALLOP trial and top-line data are anticipated by early 2019. Patients are dosed with a 750mg intravenous loading dose of ANB019 upon enrollment, followed by 100mg subcutaneously-administered monthly doses of ANB019 for a treatment period of up to 16 weeks post enrollment and followed an eight-week follow-up period. The company plans to initiate a placebo-controlled 50-patient multi-dose Phase 2 trial in PPP, also known as the POPLAR trial, where top line data is anticipated in the second half of 2019.

Second Quarter Financial Results

• Cash, cash equivalents and investments totaled $300.6 million as of June 30, 2018 compared to $324.3 million as of December 31, 2017, for a decrease of $23.7 million. The decrease primarily relates to operating cash outflow for clinical and manufacturing related expenses, as well as personnel costs.

• Research and development expenses were $10.6 million for the three months ended June 30, 2018, as compared to $7.2 million for the three months ended June 30, 2017. The increase was primarily due to continued advancement of the Company’s ANB020 and ANB019 clinical programs and additional personnel-related expenses, including share based compensation, as well as the recognition of lower research and development tax incentives during the three months ended June 30, 2018.

• General and administrative expenses were $3.8 million for the three months ended June 30, 2018, as compared to $2.4 million for the three months ended June 30, 2017. The increase was primarily attributable to additional personnel-related expenses, including share based compensation, to support the Company’s growth.

Financial Guidance

AnaptysBio expects that its cash, cash equivalents and investments will fund its current operating plan through the end of 2019.

About Etokimab

Etokimab, previously referred to as ANB020, is an antibody that potently binds and inhibits the activity of interleukin-33, or IL-33, a pro-inflammatory cytokine that multiple studies have indicated is a central mediator of atopic diseases, which we believe is broadly applicable to the treatment of atopic inflammatory disorders, such as moderate-to-severe adult atopic dermatitis, severe adult eosinophilic asthma, adult CRSwNP and potentially other allergic conditions. Following completion of a healthy volunteer Phase 1 trial of etokimab, AnaptysBio has continued clinical development of etokimab into a Phase 2a trial for moderate-to-severe adult atopic dermatitis and a 24-patient placebo-controlled Phase 2a trial in severe adult eosinophilic asthma patients where top-line data are anticipated in the third quarter 2018. AnaptysBio is enrolling its ATLAS trial, a placebo-controlled multi-dose Phase 2b clinical trial of etokimab in 300 moderate-to-severe adult atopic dermatitis patients where data is anticipated in the second half of 2019. AnaptysBio also plans to initiate its ECLIPSE trial, a randomized, placebo-controlled Phase 2 trial of etokimab in approximately 100 adult patients with CRSwNP by the end of 2018 with data anticipated in the second half of 2019.

About ANB019

ANB019 is an antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, which AnaptysBio plans to initially develop as a potential first-in-class therapy for patients suffering from generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP). AnaptysBio conducted a Phase 1 clinical trial in healthy volunteers, where 54 subjects are dosed with ANB019 and 18 are dosed with placebo in single and multi-dose cohorts at various subcutaneous and intravenously administered dose levels. In May 2018, AnaptysBio presented data from this Phase 1 clinical trial, which demonstrated favorable safety, pharmacokinetics and pharmacodynamic properties that support advancement of ANB019 into Phase 2 studies. AnaptysBio is enrolling its GALLOP trial, a Phase 2 study of ANB019 in GPP where data is anticipated in early 2019, and plans to initiate its POPLAR trial, a Phase 2 study in PPP in 2018 where data is anticipated in the second half of 2019.

On August 7, 2018 Johnson & Johnson (NYSE: JNJ) reported that it will participate in the 2018 Wells Fargo 13th Annual Healthcare Conference on Thursday, Sept. 6th, at The Westin Boston Waterfront in Boston, MA (Press release, Johnson & Johnson, AUG 7, 2018, View Source [SID1234528660]). Alex Gorsky, Chairman and Chief Executive Officer will represent the Company in a session scheduled at 9:45 a.m. (Eastern Time).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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This webcast will be available to investors and other interested parties by accessing the Johnson & Johnson website at www.investor.jnj.com.

A webcast replay will be available approximately two hours after the live webcast.