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Stemline Therapeutics Reports Third Quarter 2015 Financial Results

On November 6, 2015 Stemline Therapeutics, Inc. (Nasdaq:STML) reported financial results for the quarter ended September 30, 2015 (Press release, Stemline Therapeutics, NOV 6, 2015, View Source [SID:1234508095]).

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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.

PharmaMar’s Novel Antibody-Drug Conjugate (ADC) demonstrates anticancer activity in HER2-expressing Tumors

On November 6, 2015 PharmaMar (MSE:PHM), a world-leading biopharmaceutical company in the discovery and development of innovative marine-derived anticancer drugs, reported that its novel Antibody-Drug Conjugate (ADC) demonstrates strong anticancer activity in vitro and in vivo against tumors expressing HER2 derived from breast, gastric and ovarian cancers (Press release, PharmaMar, NOV 6, 2015, View Source [SID:1234508082]).
The novel ADC MI130004 consists of a new marine-derived tubulin inhibitor (PM050489) that is covalently bound to the HER2 antibody trastuzumab via a nonhydrolysable linker. The results have been presented today in a poster presentation during the Therapeutic Agents – Biological session at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics" taking place in Boston, November 5-9.

When tested in a panel of tumor cells expressing the receptor HER2 in their surface (HCC-194, SK-BR3 and BT-747) or tumor cells that do not express it (MCF-7 and MDA-MB-231), MI13004 demonstrated strong potency in those cells expressing the receptor. The authors found that the ADC MI130004 impairs tubulin polymerization, causing disorganization of the microtubule network leading to mitotic failures and halting cell division in cells expressing HER2, similar to the effect of the payload PM50489.

In the study, HER2-expresing tumor cells from breast, gastric and ovarian cancers were subcutaneously implanted into immunosuppressed mice to develop tumors up to certain volume (about 114 mm3). Upon treatment with MI130004 at different
doses once a week over a course of 5 weeks, mice treated with the highest dose showed substantial tumor shrinkage with complete tumor remissions in all the mice implanted with BT747 breast tumor cells that lasted up to 120 days. MI130004 was
shown to induce complete remissions in some of, but not all, the mice implanted with the breast tumor cells JIMT-1, the two gastric cancer cells Gastric-008 and N87 and the two ovarian cancer cells SK-OV-3 and A2780cis. Complete tumor remissions lasted even 385, 354 and 341 days in mice implanted with SK-OV-3, Gastric-008 and A2780cis, respectively.

The effect of MI130004 in all HER2-expressing tumors was confirmed 24h after treatment by showing mitotic aberrations in tumor cells indicating an anticancer activity mediated by microtubule inhibition and blockade of cell division.

Title: MI130004, a new ADC with a payload of marine origin shows outstanding activity against HER2-expressing tumors (Abstract A147). Session Start/End Time and location: Friday, Nov 06, 12:15 PM – 3:15 PM, session A, Hall C-D.

8-K – Current report

On November 6, 2015Mirati Therapeutics, Inc. ("Mirati") (NASDAQ: MRTX) reported financial results for the third quarter ended September 30, 2015 and provided an update on its drug development programs (Filing, 8-K, Mirati, NOV 6, 2015, View Source [SID:1234508079]).

"Over the last quarter we made substantial progress against our goals, including strengthening our balance sheet," said Charles M. Baum, M.D., Ph.D., president and CEO, Mirati. "In September, we completed a successful financing that enables us to advance all of our clinical development programs to the next stage."

Recent and Upcoming Pipeline Highlights

Operations:

· Completed a public offering of 2.25 million shares of common stock at $45.00 per share in September 2015, generating net proceeds of $94.9 million

MGCD265: Molecularly targeted kinase inhibitor

· World Conference on Lung Cancer 2015: Presented data demonstrating the favorable tolerability and clinical efficacy of MGCD265, with confirmed responses in non-small cell lung cancer (NSCLC) patients with MET and Axl gene amplification
· The poster can be found on the Company’s website at www.mirati.com
· Additional information about this clinical trial of MGCD265 is available at www.clinicaltrials.gov using identifier: NCT00697632

· The Company expects to initiate a single arm, open-label Phase 2 study in NSCLC patients, with driver alterations in MET, by the end of the year. MET alterations occur in up to 7% of NSCLC patients

MGCD516: Molecularly targeted kinase inhibitor

· European Cancer Congress (ECC) 2015: Presented interim clinical data from the ongoing Phase 1 dose escalation study of MGCD516 in patients with advanced solid tumors.
· Demonstrated that MGCD516 is well tolerated with a favorable pharmacokinetic profile
· The poster can be found on the Company’s website at www.mirati.com
· Additional information about this clinical trial of MGCD516 is available at www.clinicaltrials.gov using identifier: NCT02219711

· The Company has initiated the expansion cohorts in selected patients and expects preliminary data in 2016. The initial focus will be on NSCLC in patients with genetic driver mutations, including RET, Trk and DDR

Mocetinostat: Class I & IV HDAC inhibitor

· Announced an immuno-oncology clinical trial collaboration with MedImmune, the global biologic research and development arm of AstraZeneca, to evaluate the safety and efficacy of mocetinostat in combination with durvalumab, an investigational anti-PD-L1 immune checkpoint inhibitor. The initial Phase 2 study will be conducted in patients with NSCLC and is expected to begin in the first half of 2016

Third Quarter 2015 Financial Results

Cash, cash equivalents, and short-term investments were $138.0 million at September 30, 2015, compared to $29.3 million at December 31, 2014. In September 2015, the Company completed a public offering of 2.25 million shares of its common stock, generating net proceeds of $94.9 million. In February 2015, the Company completed a public offering of 2.6 million shares of its common stock, generating net proceeds of $48.4 million.

Research and development expenses for the third quarter of 2015 were $14.6 million, compared to $6.9 million for the same period in 2014. Research and development expenses for the nine months ended September 30, 2015 were $34.0 million, compared to $19.0 million for the same period in 2014. The increases in research and development expenses primarily reflect costs to advance the clinical development of its three oncology development programs, MGCD265, MGCD516 and mocetinostat. General and administrative expenses for the third quarter of 2015 were $4.2 million, compared to $3.7 million for the same period in 2014. General and administrative expenses for the nine months ended September 30, 2015 were $12.2 million, compared to $9.3 million for the same period in 2014. The increases in general and administrative expenses primarily reflect higher compensation costs including non-cash stock-based compensation expense.

Other income and expense, net, for the third quarter of 2015 was expense of less than $0.1 million compared to income of $1.9 million for the same period in 2014. Other income and expense, net, for the nine months ended September 30, 2015 was income of $0.1 million compared to expense of $4.6 million for the same period in 2014. Other income and expense, net, for the third quarter and nine months ended September 30, 2014 primarily reflects losses arising from the change in fair value of our warrant liability. During 2014, we amended the warrant agreements to allow for the warrants to be denominated in U.S. dollars. The amended warrants qualified for equity classification and were reclassified into stockholders’ equity.

Net loss for the third quarter of 2015 was $18.7 million, or $1.11 per share basic and diluted, compared to net loss of $8.6 million, or $0.64 per share basic and $0.72 per share diluted for the same period in 2014. Net loss for the nine months ended September 30, 2015 was $46.1 million, or, $2.86 per share basic and diluted, compared to net loss of $33.3 million, or $2.47 per share basic and diluted for the same period in 2014.

DelMar Pharmaceuticals Presents Positive Data on the Benefit of VAL-083 in Combination with Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC)

On November 6, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported data on the benefit of VAL-083 (dianhydrogalactitol) in combination with platinum-based chemotherapy regimens in the treatment of non-small cell lung cancer (NSCLC) (Press release, DelMar Pharmaceuticals, NOV 6, 2015, View Source [SID:1234508076]).

"We have recently shown that VAL-083’s mechanism is distinct from platinum-based chemotherapy, the current standard of care for NSCLC, and is active against platinum and TKI-resistant NSCLC in both in vitro and in vivo models of lung cancer," stated Jeffrey Bacha, DelMar’s president and CEO. "The data presented today further demonstrate the non-overlapping mode of action between the platinum drugs and VAL-083 and the potential for treatment synergy in combination with therapeutic regimens."

The Company presented results from a collaborative study on the potential of VAL-083 in NSCLC in a poster entitled, "Dianhydrogalactitol (VAL-083) enhances activity of platinum drugs in non-small cell lung cancer," 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), hosted by American Association for Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute, and the European Organisation for Research and Treatment of Cancer. The study was conducted in conjunction with research teams at MD Anderson Cancer Center, Shanghai Chest Hospital, and the BC Cancer Agency.

NSCLC is generally treated with surgery followed by chemotherapy with either tyrosine kinase inhibitors (TKIs) or platinum-based regimens, but long term prognosis is poor. VAL-083 is a "first-in-class" bi-functional alkylating agent with proven activity against NSCLC in preclinical and clinical studies that meditates inter-strand DNA crosslinks at N7 of guanine.

VAL-083 demonstrated clinical activity as a single agent and in combination therapy in prior clinical trials sponsored by the US National Cancer Institutes (NCI) and has been approved by the Chinese Food and Drug Administration (CFDA) for the treatment of lung cancer. Use of VAL-083 in China has been limited by a lack of modern data and preference for targeted therapies, such as TKIs, in the modern era.

The results of the study presented at AACR (Free AACR Whitepaper)-NCI-EORTC support VAL-083 as a viable treatment option for NSCLC patients who fail to respond to standard-of-care platinum-based therapy or TKI therapy, and also support potential therapeutic benefit of a VAL-083 along with platinum combination regimens in newly diagnosed patients:

VAL-083 demonstrated cytotoxic activity in all tested NSCLC cell lines, including TKI-resistant cell lines;
VAL-083 demonstrated super-additivity/synergy against NSCLC cell lines H460, A549 and H1975 when combined with either cisplatin or oxaliplatin, in vitro;
VAL-083 is less dependent on p53 for its activity than both cisplatin and oxaliplatin, and appears to have a distinct mode of action in comparison to platinum-based chemotherapy; and
The combination of VAL-083 with cisplatin significantly decreased tumor growth and increased median survival time in a xenograft A549 in vivo model of NSCLC.

"These data are aligned with our strategy to leverage VAL-083’s established clinical activity with modern biologic research to target specific, underserved markets where resistance to current standard-of-care is correlated with poor patient outcomes. This tactic establishes a personalized-medicine approach based on a potent and broadly-active chemotherapy to address significant unmet medical needs in the modern treatment of cancer," Mr. Bacha added.

SUMMARY

The purpose of the in vitro portion of this study was to investigate: 1) the role of p53 status in VAL-083 activity; 2) VAL-083 cytotoxicity in a panel of NSCLC cell lines; and 3) the combination of VAL-083 with cisplatin or oxaliplatin in NSCLC cells.

Additionally, the combination of VAL-083 with cisplatin in NSCLC was also studied in vivo. Dependence on p53 status was investigated in isogenic HCT-116p53-/- and HCT-116p53+/+ models. VAL-083, cisplatin and oxaliplatin cytotoxicity was tested in a panel of nine (9) human NSCLC cell lines: four (4) wt, four (4) mutant and one (1) null for p53. The combination potential for VAL-083 with cisplatin or oxaliplatin was investigated in three (3) human NSCLC cell lines, H460 (p53wt), A549 (p53wt) and H1975 (p53mut), by determining super-additivity and synergy using the criteria of combination index (CI)<1.

VAL-083 showed cytotoxic activity against all NSCLC cell lines in a human NSCLC panel, including TKI-resistant cell lines
VAL-083, cisplatin and oxaliplatin were tested in a panel of nine (9) human NSCLC cell lines, of which four (4) were wild-type p53 (H460, A549, H838, H226), four (4) were mutant p53 (H1975, SkLU1, H2122, H157) and one (1) was null for p53 (H1299). VAL-083 was active against all tested NSCLC cell lines, including TKI-resistant cell lines H1975, H460, and H1299, and VAL-083 activity was independent of p53 status.

VAL-083 mechanism is less dependent on p53

The dependence on p53 status was investigated in isogenic models with (HCT-116p53-/-) or without (HCT-116p53+/+) p53 knockout. Loss of p53 increased resistance to cisplatin and oxaliplatin by 3- and 6-fold, respectively, whereas the increase in resistance to VAL-083 was <2-fold. This suggests a mechanism of VAL-083 that is less dependent on wild-type p53.

VAL-083 displays synergy in combination with cisplatin or oxaliplatin in NSCLC cells H460, A549 and H1975, in vitro
The combination of VAL-083 with either cisplatin or oxaliplatin in three human NSCLC cell lines demonstrated significant super-additivity (p≤0.06) and/or synergism (CI<1) for both combinations, in vitro. Significantly, this cytotoxic effect of VAL-083 in combination with either platinum drug was observed in both TKI-resistant (H1975 and H460) and TKI-sensitive (A549) NSCLC cells, irrespective of their p53 status. These results suggest non-overlapping mechanism of action between the platinum drugs and VAL-083, and support the potential for synergistic benefit for a combination of VAL-083 and platinum-based therapies in the treatment of lung cancer, including TKI-resistant NSCLC.

VAL-083/cisplatin combination increase median survival time in A549 NSCLC model, in vivo
Rag2 mice bearing A549 xenograft tumors were treated with vehicle, 2 mg/kg cisplatin alone, or cisplatin in combination with VAL-083 (2, 2.5, or 3 mg/kg). VAL-083 in combination with cisplatin significantly and dose-dependently decreased tumor growth in the animals and increased median survival time compared to both cisplatin treatment alone and to untreated control.

Mr. Bacha added, "We continue to build a significant portfolio of data demonstrating the activity of VAL-083 against a range of tumors, independent of their p53 status. These data taken together with the historical clinical activity support the potential of VAL-083 in NSCLC. An important next step will be to initiate new clinical studies to validate the clinical activity of VAL-083 in patients with relapsed or refractory NSCLC who currently have a lack of treatment options and poor prognosis."

"Interestingly, recent literature also correlate p53 mutations with high expression of MGMT and poor outcomes in the treatment of glioblastoma multiforme (GBM). Therefore, this latest research likewise supports the potential of our ongoing clinical research with VAL-083 as a potential new therapy in the treatment of refractory GBM," concluded Mr. Bacha.

The poster highlighting the potential of VAL-083 in NSCLC may be found on DelMar’s website under View Source

About VAL-083

VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar recently announced the completion of enrollment in a Phase II clinical trial of VAL-083 in refractory GBM. Patients have been enrolled at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO).

In the Phase I dose-escalation portion of the study, VAL-083 was well tolerated at doses up to 40mg/m2 using a regimen of daily x 3 every 21 days. Adverse events were typically mild to moderate; no treatment-related serious adverse events reported at doses up to 40 mg/m2. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed in two of six (33%) of patients at 50 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment, although one patient who presented with hemorrhoids received a platelet transfusion as a precautionary measure.

Sub-group analysis of data from the Phase I dose-escalation portion of the study suggested a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083 in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

Cancer Research UK, The Lustgarten foundation and Stand Up To Cancer join forces in £8 million pancreatic cancer venture

On November 6, 2015 Cancer Research UK reported that it, The Lustgarten Foundation (link is external), and Stand Up To Cancer have come together in an international collaboration worth £8 million ($12 million) to announce funding for a pancreatic cancer research ‘Dream Team’ (Press release, Cancer Research UK, NOV 6, 2015, View Source [SID:1234508074]).

"These are among the finest researchers in the world and we’re really excited by the potential of their ideas in the fight against this terrible disease" – Dr Iain Foulkes, Cancer Research UK

This innovative funding approach, into a cancer with low survival rates and in urgent need of better treatments, will support over 24 researchers across the UK and US over the next three years.

This transatlantic ‘Dream Team’ of top researchers will tackle the toughest questions in pancreatic cancer. The initiative will research new ways to turn off faulty molecular switches in pancreatic cancer cells, which control the behaviour of a wide range of genes that can play a part in the development of the disease.

Ultimately the research aims to increase the effectiveness of chemotherapy and harness the power of the patient’s own immune system, leading to new ways to prevent pancreatic cancer from returning after initial treatment.

Professor Gerard Evan, Cancer Research UK’s co-leader of the ‘Dream Team’ and cancer gene expert at the University of Cambridge (link is external), said: "Despite the apparent diversity in pancreatic cancer, there are remarkable similarities in the biological pathways behind pancreatic tumours. Our goal is to exploit these to identify common targets for the development of more accurate and effective treatments for patients affected by this awful disease."

Around 8,500 in the UK and an estimated 40,000 people in the US will die from pancreatic cancer this year. The disease is the seventh leading cause of cancer death worldwide.

Professor Daniel Von Hoff, director of translational research at the Translational Genomics Research Institute (link is external), Arizona, who is leading the research team, said: "We’re going after pancreatic cancer in a different way. We will use new and existing drugs to reprogramme the master regulatory biological machinery in cancer cells that drives tumour growth. This machinery comprises molecular complexes of DNA and proteins that are known as ‘super enhancers’ for their ability to coordinate the expression of a large number of genes.

"By resetting the malfunctioning genome in both pancreatic tumour cells as well as the surrounding non-cancer cells on which the cancer cells rely for support, the team will try to increase the sensitivity of tumours to chemotherapy and make them vulnerable to the patient’s immune response."

Kerri Kaplan, executive director and chief operating officer of The Lustgarten Foundation, said: "To eradicate pancreatic cancer will take a collaborative effort and private funding plays a critical role in accelerating the development of new clinical trials for this deadly disease. This international collaboration will bring together leading global experts in the field of pancreatic cancer research, and together, we will focus on developing new therapies and innovative approaches so patients can benefit and live longer lives."

Dr Iain Foulkes, Cancer Research UK’s executive director of research funding, said: "Survival from pancreatic cancer is low – only three percent of patients in the UK survive their disease for five years or more. Frankly, progress has not been good enough and it’s why we have invested nearly £4 million in this ‘Dream Team’. These are among the finest researchers in the world and we’re really excited by the potential of their ideas in the fight against this terrible disease."