On November 6, 2015 Stemline Therapeutics, Inc. (Nasdaq:STML) reported financial results for the quarter ended September 30, 2015 (Filing, 8-K, Stemline Therapeutics, NOV 6, 2015, View Source [SID:1234508072]).

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "During the third quarter, we made significant progress on many fronts as we continue to advance our clinical programs forward. We are actively enrolling patients, and opening additional sites, in the expansion stage of our ongoing SL-401 pivotal trial in blastic plasmacytoid dendritic cell neoplasm, BPDCN. We look forward to sharing clinical updates from both the lead-in and initial expansion stages of this trial at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) meeting this December, and on into next year."

Dr. Bergstein continued, "We remain focused on the BPDCN indication while continuing to pursue expansion opportunities for SL-401 in additional malignancies. We have single agent trials currently open in several indications and we anticipate combination studies coming on-line as well. We are also continuing to develop our other pipeline candidates, SL-701 and SL-801, and look forward to treating our first patient with SL-801, our novel XPO1 inhibitor, early next year. With a strong cash position and multiple ongoing programs advancing across a range of indications of unmet medical need, we remain focused on achieving our objective of building a leading commercial stage biopharmaceutical company."

Third Quarter 2015 Financial Results Review

Stemline ended the third quarter of 2015 with $104.0 million in cash, cash equivalents and investments, as compared to $58.6 million as of December 31, 2014. In the first quarter of 2015, the Company completed an equity offering raising $68.6 million in gross cash proceeds on the sale of 4.4 million common shares.

For the third quarter of 2015, Stemline had a net loss of $9.2 million, or $0.53 per share, compared with a net loss of $6.9 million, or $0.53 per share, for the same period in 2014.

Research and development expenses were $7.3 million for the third quarter of 2015, which reflects an increase of $2.3 million compared with $5.0 million for the third quarter of 2014. The higher expenses during the third quarter were primarily attributable to the ramp up of SL-401 and SL-701 clinical activities. Also, we incurred costs relating to SL-801 IND-enabling studies.

General and administrative expenses were $2.2 million for the third quarter of 2015, which reflects an increase of $0.2 million compared with $2.0 million for the third quarter of 2014. The higher costs were primarily attributable to an increase in non-cash stock based compensation expense relating to employees.

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On November 6, 2015 PharmaMar (MSE:PHM) reported that the Company will showcase several clinical studies with YONDELIS (trabectedin) in soft tissue sarcoma (STS) during the 20th anniversary CTOS (Connective Tissue Oncology Society) meeting that will be held in Salt Lake City, Utah, from the 4-7 November, 2015 (Press release, PharmaMar, NOV 6, 2015, View Source [SID:1234508070]). This forum will gather oncologist experts and investigators to share new results and experiences to move forward basic and applied research on connective tissue-related cancers.

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In addition to presenting several studies for YONDELIS (trabectedin) in STS, PharmaMar has organized a stand-alone meeting in which Javier Martín Broto, MD, President of the Spanish Sarcoma Research Group and Peter Reichardt, MD, Professor and Head of the Hematology and Oncology Department, Sarcoma Center HELIOS Klinikum Bad Saarow, Germany, have discussed the clinical development story of YONDELIS in STS.

During his presentation, Dr. Martín Broto has showcased the pivotal studies that led to the approval in the European Union and the U.S., the clinical trial STS-201 and the SAR-3007ii, respectively. To date, approximately 50.000 pacientes have been treated with YONDELIS worldwide. The expert has pointed out how everything started with the authorization of commercialization of YONDELIS for soft tissue sarcoma by the European Commission, resulting in the first anticancer drug of marine origin.

Trabectedin, an effective therapy in second line treatment

Trabectedin is an anticancer drug that has shown to decrease tumor density and to induce tumor shrinkage, two clinical measurements that should be considered in patients treated with this drug when assessing tumor responseiii. "Understanding
how to correctly define tumor progression in patients treated with trabectedin is important for the decision making strategy to prevent interruption of a treatment that may provide clinical benefit after 6 cycles of treatment, in some cases" added Dr. Martín Broto. This is one of the main points that were concluded from the clinical trials carried out by the French sarcoma Group in 2015, which include the large retrospective study called Retrospectyon, and the prospective trial T-DIS. The oncologist Dr. Martín Broto added that "when patients continued receiving trabectedin until disease progression, instead of stopping the treatment after 6
cycles, the next disease relapse is delayed."

Since 2003 when the first clinical study started until now, trabectedin has demonstrated that it is the treatment of choice for pacients with STS treated in the second-line setting as "this drug provides prolonged survival, has an optimal safety profile, has received approval for all subtypes of STS and it is currently included in the ESMO (Free ESMO Whitepaper) Clinical Guidelines and very soon will be also in the NCCN Clinical Practice Guidelines".

Main studies presented at CTOS

 Y-IMAGE study: a non-interventional, prospective phase IV study of trabectedin in patients with advanced soft tissue sarcoma (STS). Main author: Penel et al.

 Efficacy and safety of trabectedin as an early treatment for advanced STS: an interim analysis of a non-interventional, prospective Phase IV study. Main author: Mazzeo et al.

 Trabectedin in elderly patients with recurrent soft tissue sarcoma (STS): an interim analysis of a non-interventional, prospective Phase IV study. Main author: Buonadonna et al.

 Final results of two phase II studies, a randomized comparative study and a single arm study, of trabectedin in patients (PTS) with translocation-related sarcomas (TRS) – patrocinado por Taiho Pharmaceuticals. Main author: Kawai, A et al.

 Single-center experience of high-grade chondrosarcoma treated with trabectedin – patrocinado por Janssen Research & Development, LLC. Main author: Chawla.

 Final Overall Survival (OS) Analysis of the Randomized Phase 3 Study of Trabectedin (T) or Dacarbazine (D) for the Treatment of
Patients (pts) with Advanced Leiomyosarcoma (LMS) or Liposarcoma (LPS) – patrocinado por Janssen Research & Development, LLC. Main author: Shreyaskumar R. Patel, Margaret von Mehren, Damon.

 Efficacy and Safety of Trabectedin (T) or Dacarbazine (D) in an Elderly Patient subgroup (+65 years) with Advanced Leiomyosarcoma (LMS) or Liposarcoma (LPS) after Prior Chemotherapy – patrocinado por Janssen Research & Development, LLC. Main author: Margaret von Mehren, George D. Demetri, Scott M Sc

 Efficacy and Safety of Trabectedin(T) or Dacarbazine (D) for Treatment of Patients (pts) with Advanced Leiomyosarcoma (LMS)
or Liposarcoma (LPS) after Prior Chemotherapy – patrocinado por Janssen Research & Development, LLC. Main author: George D.
Demetri, Shreyaskumar R. Patel, Samuel Th

 Trabectedin in patient with an abdominal small round cells desmoplastic tumour: a case report. Main author: J. Casanova, P.
Tavares, R. Ferreira

 Analysis of trabectedin safety in teenage young adults with STS. Cambridge University Hospital-Addrnbrookes

About YONDELIS (trabectedin)

YONDELIS (trabectedin) is a novel, multimodal, synthetically produced antitumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. The drug exerts its activity by targeting the transcriptional machinery and impairing DNA repair. It is approved in 80 countries in North America, Europe, South America and Asia for the treatment of advanced soft tissue sarcomas as a single-agent and for relapsed ovarian cancer in combination with DOXIL/CAELYX (doxorubicin HCl liposome injection). Under a licensing agreement with PharmaMar, Janssen Products, L.P. has the rights to develop and sell YONDELIS globally except in Europe, where PharmaMar holds the rights, and in Japan, where PharmaMar has granted a license to Taiho Pharmaceuticals.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a type of cancer originating in the soft tissues that connect, support and surround other body structures, such as muscle, fat, blood vessels, nerves, tendons and the lining of jointsiv,v. In the United States, nearly 12,000 people will be diagnosed and approximately 4,870 are expected to die of soft tissue sarcomas in 2015.

On November 06, 2015 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel nucleic acid-based therapeutics for oncology and rare diseases, reported its financial and operational results for the third quarter ended September 30, 2015 (Press release, Idera Pharmaceuticals, NOV 6, 2015, View Source;p=RssLanding&cat=news&id=2107923 [SID:1234508068]).

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"We’ve made a great deal of progress at Idera through the first three quarters of 2015, which sets up our company for a number of important catalysts in this last quarter of the year," stated Vincent Milano, Idera’s Chief Executive Officer. "As we announced yesterday, we will be presenting the clinical and safety data analysis from our Phase 1/2 clinical trial of IMO-8400 in Waldenström’s macroglobulinemia at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December. We also are initiating our clinical studies of our TLR9 agonist, IMO-2125 in combination with ipilmumab in patients with metastatic melanoma and IMO-8400 Phase 2 study in dermatomyositis, this quarter. Finally, as detailed in the following text, we are today announcing the first two gene targets for our third generation antisense technology platform."

Continued Milano, "I’m very pleased with the progress that our team at Idera has made over the past months and quarters as we’ve integrated the existing Idera team with many new contributors all the while maintaining the rigor and momentum to ensure our company is positioned for both near and long-term success."

Research and Development Program Updates

IMO-8400 and IMO-2125 are our lead clinical development drug candidates. IMO-8400 is an oligonucleotide-based antagonist of Toll-like receptors (TLRs) 7, 8, and 9. IMO-2125 is an oligonucleotide-based agonist of TLR9.

Toll-like Receptor (TLR) Agonism Program

Immuno-Oncology Program

In June 2015, the company announced that it had entered into a strategic clinical research alliance with MD Anderson Cancer Center to advance the clinical development of intra-tumoral TLR9 agonists in combination with checkpoint inhibitors. The company also announced that it expects to initiate the first trial from the alliance, a Phase 1/2 study to assess the safety and efficacy of intra-tumoral IMO-2125 in combination with ipilimumab in approximately 45 patients with metastatic melanoma. The company is on track to initiate this study in the fourth quarter of 2015. Planning of additional studies as part of the clinical research alliance with MD Anderson Cancer Center is in progress. Additionally, the company presented new preclinical data demonstrating the combination of IMO-2125 and PD1 in cancer models at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on November 5th in Boston, MA.

Toll-like Receptor (TLR) Antagonism Programs

Genetically Defined Forms of B-cell Lymphoma

Idera’s program in genetically defined forms of B-cell lymphoma is based on pre-clinical studies that have demonstrated, in certain B-cell lymphomas that the presence of the MYD88 L265P oncogenic mutation led to over-activation of TLR7 and TLR9 signaling and that blocking these TLRs with our antagonists promoted tumor cell death.

In the company’s Phase 1/2 study in Waldenstrom’s macroglobulinemia, the targeted number of patients at each of the three dose levels completed assessment through the end of their first cycle of treatment; the dose escalation portion of the study has also been completed. The trial is designed to evaluate IMO-8400’s safety, tolerability and potential clinical activity in patients who have a history of relapse after or failure to respond to prior therapies. Idera announced yesterday that data from this Phase 1/2 clinical study will be presented as a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Saturday, December 5th from 5:30 PM ET – 7:30 PM ET.

During the third quarter the company also continued to enroll patients into the first of three dose cohorts of our Phase 1/2 clinical trial of IMO-8400 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are harboring the MYD88 L265P oncogenic mutation. The company currently anticipates that data from this trial will become available in 2016.

Idera previously announced that the U.S. Food and Drug Administration (FDA) granted us orphan drug designation for IMO-8400 for the treatment of Waldenström’s macroglobulinemia and DLBCL.

Rare Disease Programs

The company is planning to initiate clinical development of IMO-8400 for the treatment of rare autoimmune and autoinflammatory diseases. The company has selected dermatomyositis and Duchenne muscular dystrophy (DMD) as the first rare diseases for which we plan to develop IMO-8400. The company selected these indications for development based on the reported increase in TLR expression in these disease states, expression of cytokines indicative of key TLR-mediated pathways, the identification of prospective biomarkers for evaluation in early clinical trials and significant unmet needs. The company plans to progress clinical development in these two indications by initiating a Phase 2 clinical trial in dermatomyositis in the fourth quarter of 2015 and a Phase 2 clinical trial in DMD in 2016.

Third Generation Antisense Platform

Throughout 2015, the company undertook an analysis and prioritization of oncology and rare disease indications for potential development of drug candidates derived from our third generation antisense technology platform. The key considerations in identifying disease indications from our third generation antisense program included: strong evidence that the disease is caused by a specific protein; clear criteria to identify a target patient population; biomarkers for early assessment of clinical proof-of-concept; a targeted therapeutic mechanism for action; and unmet medical need to allow for a well-defined development path to approval and commercial opportunity. As a result of this analysis, the company has selected NLRP3 (NOD-like receptor family, pyrin domain containing protein 3) and DUX4 (Double Homeobox 4) as gene targets to advance into IND-enabling activities, which will occur throughout 2016. Potential disease indications include, but are not limited to interstitial cystitis, uveitis and facioscapulohumeral muscular dystrophy (FSHD), respectively. The company intends to describe these programs in more detail during the 2016 JP Morgan Healthcare Conference early next year.

Financial Results

Third Quarter 2015 Results
Net loss applicable to common stockholders for the three months ended September 30, 2015 was $11.4 million, or $ (0.10) per diluted share, compared to a net loss applicable to common stockholders of $9.6 million, or $ (0.11) per diluted share, for the same period in 2014. For the nine month period ended September 30, 2015, the Company’s net loss applicable to common stockholders was $36.6 million, or $ (0.32) per diluted share, compared to a net loss applicable to common stockholders of $27.1 million, or $ (0.33) per diluted share, for the same period in 2014. The company recognized nominal revenue in the third quarter and nine month periods of 2015 and 2014.

Research and development expenses for the three months ended September 30, 2015 totaled $7.5 million compared to $6.7 million for the same period in 2014. For the nine month period ended September 30, 2015, research and development expenses totaled $25.1 million compared to $19.2 million for the same period in 2014.

General and administrative expenses for the three months ended September 30, 2015 totaled $4.0 million compared to $2.9 million for the same period in 2014. For the nine month period ended September 30, 2015, general and administrative expenses totaled $11.7 million compared to $7.6 million for the same period in 2014.

As of September 30, 2015, Idera’s cash, cash equivalents and investments totaled $94.7 million compared to $48.6 million as of December 31, 2014.

On November 6, 2015 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported new preclinical data on varlilumab, a fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade (Press release, Celldex Therapeutics, NOV 6, 2015, View Source [SID:1234508066]). Results suggest that cancers may respond to CD27 immune modulation by independent mechanisms, such as immune co-stimulation and regulatory T cell (Treg) depletion. Varlilumab has the unique ability to act through both of these mechanisms. The new data were presented in a poster entitled "The mechanism of anti-tumor immunity induced by varlilumab, a CD27 agonist mAb, is model dependent" at the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

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"Our data show that CD27 modulation through varlilumab results in immune activation and suppression of Treg activity, either of which can be independently responsible for a therapeutic effect, depending on the cancer model," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "Because individual human cancers are also likely to have different sensitivities to these anti-tumor activities, varlilumab’s ability to act through both mechanisms provides the broadest potential for therapeutic benefit. Our collection of preclinical and clinical results to date support Celldex’s broad clinical development program across tumor types and in combinations with other anti-tumor agents."

To better understand each mechanism separately, scientists engineered varlilumab to possess either strong co-stimulatory activity (varli-mG1) or strong Treg suppression activity (varli-mG2a) and analyzed their efficacy in several preclinical tumor models. The data indicated that potent co-stimulation activity was required for therapeutic activity in a BCL1 lymphoma model, whereas control of Tregs was required for activity in several other models, such as E.G7 thymoma, CT26 colorectal and colon 26. Importantly, varlilumab has a combination of immune co-stimulation and Treg depleting activity and demonstrated potent anti-tumor activity in all the models.

The immune stimulating and Treg depleting effects of varlilumab were also observed in Celldex’s Phase 1, single-agent clinical trial of varlilumab in patients with refractory, advanced cancers. Specifically, varlilumab administration was associated with a rapid and transient induction of pro-inflammatory cytokines, activation of T cells as assessed by increased HLA-DR expression and a significant decrease in circulating Tregs. The study also demonstrated promising clinical activity. Two patients experienced durable objective responses including a complete response in Hodgkin lymphoma (18.9+ months) and a partial response in renal cell carcinoma (13.6+ months). Thirteen patients experienced stable disease (3-36.2+ months). Varlilumab was very well tolerated and demonstrated minimal toxicity, even in elderly patients. There was no indication of immune-mediated adverse events often seen with other immunotherapies.

Varlilumab is currently being studied in multiple ongoing Phase 1/2 clinical trials with several anti-tumor agents, including nivolumab (Opdivo), ipilimumab (Yervoy) and sunitinib (Sutent) in advanced-stage cancers. Efforts are underway for additional Phase 2 studies with varlilumab, including a combination with atezolizumab (Roche’s anti-PDL1 antibody), and the Company will provide updates on these studies as they are initiated.

On November 5, 2015 AskAt reported that it has received a notice of allowance dated November 5, 2015 from Korea Intellectual Property Rights Information Service (KIPRS) in connection with the Application No. 10-2011-7027678, a use patent of EP4 receptor antagonist for the treatment of Cancer (Press release, AskAt, NOV 5, 2015, View Source [SID1234535066]).

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