On March 14, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the fourth quarter and full year 2015 and commented on recent accomplishments and clinical development plans for its pipeline of several SINE-based therapeutics including selinexor, its lead product candidate (Press release, Karyopharm, MAR 14, 2016, View Source [SID:1234509521]).

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"During 2015, we continued to expand our leadership position in the development of oral SINE-based oncology and non-oncology therapies with clinical advancement of selinexor across a number of hematologic and solid tumor indications and the presentation of encouraging data on our earlier-stage pipeline programs," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "Our broad and aggressive oncology clinical development program continues in 2016 with both company- and investigator-sponsored trials underway or planned to evaluate selinexor both as a single-agent and in combination with other existing and emerging oncology therapies. In addition, we made important progress with our non-oncology focused SINE compounds in a number of disease areas in which XPO1 is critically involved. We look forward to several potentially value-creating data readouts over the next 18 months."

Clinical Development Plans:
Selinexor in hematologic malignancies. Karyopharm is actively enrolling patients in several later phase clinical studies evaluating single-agent selinexor in hematologic malignancies, including patients with relapsed/refractory multiple myeloma (MM) (STORM study), older patients with relapsed/refractory acute myeloid leukemia (AML) (SOPRA study) and patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (SADAL study). Karyopharm expects data from the first 80 patients in the STORM study to be available in mid-2016, at which point, it will evaluate whether to expand the study. Karyopharm also expects to provide an interim analysis update from the SOPRA study in late-2016 with top-line data expected in mid-2017. Based on discussions with the U.S. Food and Drug Administration (FDA), Karyopharm amended the protocol for the ongoing SADAL study to remove dexamethasone from the regimen and to evaluate selinexor as a single-agent in this patient population. The study will continue to compare 60 mg and 100mg twice weekly doses of selinexor with 100 patients per arm and at least 50% of patients with GCB-type DLBCL. Based on these amendments, the company expects to report top-line data from this study in early 2017.

Single-agent selinexor in solid tumors. Karyopharm is currently conducting company-sponsored trials of single-agent selinexor in three solid tumor indications including advanced unresectable dedifferentiated liposarcoma (SEAL study), heavily pretreated patients with gynecologic malignancies (SIGN study) and recurrent glioblastoma multiforme (KING study). Karyopharm is planning to present updated data from the SIGN and KING studies at an appropriate medical meeting in mid-2016. The Phase 2/3 SEAL study, evaluating single-agent oral selinexor versus placebo, was initiated earlier this year based on promising clinical data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2015 Annual Meeting in which durable stable disease and improvement in progression free survival compared to previous chemotherapies were observed. Top-line data from the Phase 2 portion of this study are expected in mid-2017.

Selinexor combinations. A number of investigator-sponsored and company-sponsored trials evaluating selinexor in combination with either chemotherapy or targeted agents in hematologic and solid tumor indications are currently ongoing or planned. In mid-2016, Karyopharm plans to initiate a Phase 2/3 study (SCORE study) evaluating the combination of selinexor, carfilzomib and dexamethasone in patients with refractory MM who were previously treated with a proteasome inhibitor and an immunomodulatory agent. In addition, Karyopharm expects to report top line data from the Phase 1 portion of a Phase 1b/2 study (STOMP study) evaluating selinexor in combination with commonly used treatments, including bortezomib, pomalidomide, or lenalidomide, for relapsed/refractory MM in late-2016.

KPT-8602, second generation SINE compound. In January 2016, Karyopharm initiated a Phase 1/2 study of oral KPT-8602, a novel, second generation, SINE compound, in patients with relapsed/refractory MM. Data from preclinical studies presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrated single-agent anti-MM activity of KPT-8602 along with the potential for higher and/or more frequent dosing compared with selinexor. Top-line safety and tolerability data from this Phase 1/2 study are expected in late 2016.

KPT-9274, oral dual inhibitor of PAK4 and NAMPT. In mid-2016, Karyopharm plans to initiate clinical development in patients with heavily pretreated solid tumors or lymphoma for its oral dual inhibitor of PAK4 and NAMPT, KPT-9274.

Verdinexor (KPT-335). In May 2015, Karyopharm began clinical testing of verdinexor in a randomized, double-blind, placebo-controlled, dose-escalating Phase 1 clinical trial in healthy human volunteers in Australia. Verdinexor was found to be generally safe and well tolerated. Karyopharm is preparing to advance verdinexor for certain viral indications with an initial focus on influenza. Preclinical data provide strong support for other potential indications for verdinexor, including human immunodeficiency virus (HIV).
KPT-350. KPT-350 is an investigational new drug application-ready oral compound with a preclinical data package supporting potential efficacy in a number of neurological, autoimmune and inflammatory conditions. We plan to partner with a collaborator to undertake the clinical development and potential commercialization of KPT-350 in one or more mutually agreed indications.

Scientific Presentations and Publications:
Positive clinical data demonstrating the activity and tolerability of selinexor across multiple hematologic malignancies including MM and AML were presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held in December 2015 in Orlando, Florida.

Updated data from an ongoing investigator-sponsored trial of selinexor in combination with carfilzomib and dexamethasone in refractory MM were presented by Andrzej Jakubowiak, MD, PhD, from The University of Chicago. The data demonstrated encouraging efficacy of selinexor in combination with carfilzomib and dexamethasone in heavily pretreated patients with highly refractory MM, including patients whose disease is refractory to previous carfilzomib-based combinations, suggesting the potential of this combination to overcome carfilzomib resistance. Based on these data, Karyopharm expects to initiate a Phase 2/3 clinical study (SCORE study) in mid-2016.

Karyopharm researchers and collaborators also presented preclinical data demonstrating the potential of selinexor to synergize with proteasome inhibitors to overcome drug resistance in MM.

Karyopharm presented data demonstrating the activity and tolerability of selinexor in combination with standard of care agents in the AML setting, including data from a Phase 2 trial investigating the efficacy and tolerability of selinexor in combination with arabinoside cytosine (Ara-C) and idarubicin in "fit" patients with relapsed and/or refractory AML. Karyopharm also presented data from a Phase 1 study determining the safety and efficacy of selinexor in combination with fludarabine and cytarabine in pediatric patients with relapsed and/or refractory acute leukemia.

Karyopharm researchers presented data establishing 60mg as the most appropriate selinexor dose for both efficacy and tolerability across many hematologic and solid cancers. These data support the selinexor first-in-human Phase 1 clinical trial solid tumor data published in Journal of Clinical Oncology in March 2016, which recommended a dose of 60mg given twice a week as the Phase 2 dose. This recommendation was based on superior patient tolerability, longer duration of therapy, and no demonstrable improvement in radiologic response or disease stabilization compared with higher doses.

Fourth Quarter and Year Ended December 31, 2015 Financial Results

Cash, cash equivalents and investments as of December 31, 2015, including restricted cash, totaled $210.0 million, compared to $214.8 million as of December 31, 2014.

For the year ended December 31, 2015, research and development expense was $97.7 million compared to $60.1 million for the year ended December 31, 2014. For the year ended December 31, 2015, general and administrative expense was $21.6 million compared to $15.9 million for the year ended December 31, 2014. The increase in research and development expense resulted primarily from the increase in expenses related to the continued clinical development of selinexor. The increase in general and administrative expense resulted primarily from an increase in personnel costs, including stock-based compensation expense.

Karyopharm reported a net loss of $118.2 million, or $3.32 per share, for the year ended December 31, 2015, compared to a net loss of $75.8 million, or $2.43 per share, for the year ended December 31, 2014. Net loss includes stock-based compensation expense of $17.1 million and $14.2 million for the years ended December 31, 2015 and 2014, respectively.

For the quarter ended December 31, 2015, research and development expense was $24.1 million compared to $20.0 million for the quarter ended December 31, 2014. For the quarter ended December 31, 2015, general and administrative expense was $5.3 million compared to $5.9 million for the quarter ended December 31, 2014. The increase in research and development expenses resulted primarily from the increase in expenses related to the continued clinical development of selinexor.

Karyopharm reported a net loss of $29.0 million, or $0.81 per share, for the quarter ended December 31, 2015, compared to a net loss of $25.9 million, or $0.79 per share, for the quarter ended December 31, 2014. Net loss includes stock-based compensation expense of $5.4 million and $4.6 million for the quarters ended December 31, 2015 and December 31, 2014, respectively.

Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents will fund its research and development programs and operations into the middle of 2018, including advancing the four later-stage clinical studies to their next data inflection points. Karyopharm expects to end 2016 with at least $120 million in cash, cash equivalents and investments.

On March 14, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported financial results for the quarter ended December 31, 2015 (Press release, Stemline Therapeutics, MAR 14, 2016, View Source [SID:1234509512]).

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Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "During the fourth quarter, we made significant progress across all three of our development programs. Key achievements included 1) generating and presenting data from our ongoing Phase 2 trial of SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN) which we have designed to support potential registration, 2) treating our first patient in the second stage of our Phase 2 program of SL-701 in advanced brain cancer, and 3) the opening of our IND for SL-801 on schedule. At the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December, we presented very strong data from our ongoing SL-401 trial in BPDCN, demonstrating a high overall response rate in BPDCN, with multiple complete responses. We are also very pleased with the pace of enrollment in BPDCN, and note that we are tracking in-line with our expectations. We look forward to sharing key clinical and regulatory updates on SL-401 throughout this year."

Dr. Bergstein continued, "We continue to evaluate SL-401 in several additional malignancies that overexpress IL-3R. Specifically, we have single agent trials enrolling AML patients with minimal residual disease and patients with advanced high-risk myeloproliferative neoplasms. We also expect our first clinical studies that combine SL-401 with other therapies will begin this year."

Dr. Bergstein concluded, "Our other pipeline candidates, SL-701 and SL-801, continue to advance. Our SL-701 trial is currently enrolling patients and we expect updates from this program in the second half of the year. The SL-801 IND is open, and we are on track to treat our first patient this quarter. With our strong cash position, we believe we have sufficient financial resources to achieve significant clinical and regulatory milestones this year and beyond."

Fourth Quarter 2015 Financial Results Review

Stemline ended the fourth quarter of 2015 with $97.5 million in cash, cash equivalents and investments, as compared to $104.0 million as of September 30, 2015, which reflects a cash burn of $6.5 million for the quarter. The company ended the fourth quarter of 2015 with 18.2 million shares outstanding.

For the fourth quarter of 2015, Stemline had a net loss of $10.2 million, or $0.58 per share, compared with a net loss of $6.9 million, or $0.53 per share, for the same period in 2014. The net loss for full year 2015 was $37.2 million, or $2.15 per share, as compared with a net loss of $28.8 million, or $2.23 per share, in the prior year.

Research and development expenses were $7.9 million for the fourth quarter of 2015, which reflects an increase of $2.8 million, or 56%, compared with $5.1 million for the fourth quarter of 2014. The increase in expenses during the current quarter was primarily attributable to the ramp up in our clinical trial activities for SL-401 and SL-801.

General and administrative expenses were $2.6 million for the fourth quarter of 2015, which reflects an increase of $0.6 million, or 30%, compared with $2.0 million for the fourth quarter of 2014. The increase in expenses during the current quarter was primarily attributable to an increase in compensation expense relating to administrative employees.

On March 11, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported positive preclinical findings generated using the Company’s Immune Repertoire Capture technology, presented at the Keystone Symposia Conference "Antibodies as Drugs", which took place in Whistler, British Columbia, Canada, March 6-10, 2016 (Press release, Atreca, MAR 11, 2016, View Source [SID1234522968]). Atreca’s programs are advancing multiple therapeutic agents that have shown they can enhance elimination of cancer cells, based on the analysis of successful anti-tumor responses in patients .

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In a poster titled, "Expanded IgG Lineages in Lung Cancer Non-Progressors Reveal Anti-Tumor Antibodies" (Abstract No. X2 1014), a research team of scientists at Atreca and collaborators at leading institutions reported key preclinical research findings, including:

Immune Repertoire Capture technology generated the sequences of native antibodies from the active immune response of an individual with Stage 4 lung adenocarcinoma who had experienced long-term non-progression of disease.
Several of these antibodies have been shown to bind tumor tissue but not normal tissue, and some bind multiple tumor types beyond the cancer type of the original patient from which the antibodies were discovered.
Select antibodies demonstrated they can destroy tumor cells, as measured by antibody-dependent cellular cytotoxicity (ADCC) in in vitro assays.
Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research, stated, "By analyzing blood samples from one patient at the single cell level using Atreca’s Immune Repertoire Capture platform, we identified thousands of antibodies and were able to generate natively paired antibody heavy and light chain sequences from blood plasmablasts, which are activated B cells that play a critical role in immune responses. Analysis of these antibody sequences allowed us to select and express functional antibodies for further analysis. Multiple patient-derived antibodies were found to bind cells from multiple tumor types, which highlights the utility and efficiency of our approach."

Select antibodies discovered in Atreca’s research have progressed to preclinical testing in in vivo models of cancer, with the goal of selecting candidates to enter into more advanced preclinical studies, based on a detailed understanding of anti-tumor immune responses.

"The results disclosed at Keystone this week demonstrate the power of Atreca’s Immune Repertoire Capture platform and its ability to generate novel antibodies that can target cancer," commented Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "Our technology allows Atreca to mine the key phenomenon driving efficacious anti-cancer immune responses—a patient’s own anti-tumor immunity—with the goal of using this knowledge to help other patients fight their disease." Dr. Serafini added, "We are grateful to our collaborators for their dedication to this research and look forward to the continued progress of our lead efforts into the clinic."

On March 11, 2016 PharmaMar reported that the creation of a network of centres of reference and adopting measures that promote research and access to treatments are two key aspects for improving the prognosis of patients with soft tissue sarcoma (STS), an uncommon type of cancer that originates in the tissues that connect, support and surround other body structures, such as muscles, fat, blood vessels, nerves, tendons and lining of the joints (Press release, PharmaMar, MAR 11, 2016, View Source [SID:1234510444]).

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This is one of the conclusions of the renowned international oncologists during the presentation of the Soft Tissue Sarcoma: Evidence and Experience seminar. This meeting, organised by PharmaMar, will bring leading world experts in this disease to Barcelona on 11 and 12 March from, among other countries, the United Kingdom, France, Italy, Germany, Spain and the United States, to analyse the latest advances in its diagnosis and treatment.

"We are proud to lead this meeting, where the most influential oncologists in the world in sarcoma management share opinions, present new case reports, discuss the latest advances and the most effective treatments for these patients", explained Mr Luis Mora, General Manager of the PharmaMar Oncology Unit.

Incidence of sarcoma

According to figures quoted by Prof Jean-Yves Blay, Chair of the European Organisation for the Research and Treatment of Cancer (EORTC), STS represents less than 1% of adult cancersi. "There are more than 50 histological subtypes of soft tissue sarcoma. The most common are leiomyosarcoma and liposarcoma. In Europe, the incidence of this type of tumour in adults (not including gastrointestinal stromal tumour) is from 4 to 5 cases per 100,000 inhabitantsii and approximately 2 half of the patients diagnosed with soft tissue sarcoma have developed metastases or are expected to do so", said Prof Blay.

To prevent patients reaching the expert sarcoma team after having been operated on, measures are required to guarantee an appropriate diagnosis and treatment agreed upon by a multidisciplinary team. Dr Javier Martín Broto, Chair of the Spanish Sarcoma Research Group (GEIS), maintains that this coordination requires the creation of a network of centres of reference to guarantee that patients with suspected soft tissue sarcoma are diagnosed and treated by teams of experts in the disease. "Studies show that patients who are diagnosed and treated in a centre of reference specialising in soft tissue sarcoma survive for longer than those diagnosed and treated in a centre without such specialisation", he explained.

This is precisely one of the lines of research of the Spanish Sarcoma Research Group which, according to Dr Martin Broto, has been collaborating for years with the Ministry of Health for the recognition of sarcoma hospitals and CSUR (Centres, Services and Units of Reference) teams. In his opinion, "we are currently in the final phase and we expect these centres to be made official in the near future".

The Spanish Sarcoma Research Group was created in 1994 and has led 47 research projects that have included thousands of patients. In the last few years, it has sponsored a large number of international clinical trials and its protocols are used worldwide.

Advances in the treatment of soft tissue sarcoma

Professor George Demetri, Director of the Centre for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute (Boston), presented the latest research projects related to the treatment of sarcoma, including the study conducted with trabectedin (Yondelis) in the United States, in which the compound was shown to reduce the risk of disease progression versus conventional treatment. Yondelis is developed and marketed by PharmaMar in Europe, while Janssen Products, L.P. has the rights to develop and sell Yondelis in the rest of the world except Japan, where PharmaMar has signed a licensing agreement with Taiho Pharmaceutical. 3

"Since Yondelis was first approved in Europe in 2007, approximately 50,000 patients in 80 countries have benefited from this therapy in all its indications", said Prof. Demetri, who explained that "advanced soft tissue sarcoma is a complex set of uncommon diseases that are virtually always life-threatening for patients with advanced stage disease. Patients need new treatment options that are more effective and well tolerated, and renewed hope has come with new drug approvals in the past decade based on sophisticated scientific research".

According to the data provided by this expert, the Phase 3 multicentre trial in the United States, Brazil and Australia is one of the largest conducted to date in sarcoma patients. This study showed a significant improvement in disease control (called "progression-free survival") with trabectedin versus dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) after failure of prior standard therapy with an anthracycline and at least one other chemotherapy.

All the experts present highlighted the importance of these advances in the treatment of sarcoma, a rapidly progressing form of cancer that requires new treatment options. "In soft tissue sarcoma, disease stabilisation is useful for evaluating the success of the treatment in advanced stage patients. The data from the latest clinical trials with Yondelis offer a more hopeful future for patients and a path forward for even more research to improve clinical outcomes", concluded Dr Demetri.