On November 13, 2018 RadioMedix Inc. (a Texas-based clinical stage biotechnology company) and Orano Med (a nuclear biotechnology company) reported that the United States Food & Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to AlphaMedixTM for the treatment of neuroendocrine tumors (NETs) (Press release, RadioMedix, NOV 13, 2018, View Source [SID1234531347]). AlphaMedixTM is a 212Pb-labeled somatostatin analogue used for the targeted alpha therapy (TAT) of neuroendocrine tumors (NETs).

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"TAT has brought new hope to our patients with cancer, and the range of available therapies in this area will only increase in the near future. We are pleased to conduct the first TAT clinical trial in the U.S. for neuroendocrine cancers, with the aim of registration of the drug," said Dr. Ebrahim S. Delpassand, CEO of RadioMedix and Medical Director of the clinical studies. "We are hoping that AlphaMedixTM will provide a breakthrough therapy that will benefit our patients soon," added Dr. Delpassand. "We are excited about the progress of our dose escalation studies of AlphaMedixTM", echoed Dr. Izabela Tworowska, Ph.D., CSO of RadioMedix.

The mechanism of action of AlphaMedixTM relies on the delivery of a cytotoxic load of alpha-emitters to SSTR-overexpressing neuroendocrine tumors. Alpha- emitters are highly energetic radioactive particles that can cause irreversible damage to the cancer cells. RadioMedix and Orano Med initiated the Phase 1 clinical trial of the safety and preliminary efficacy of AlphaMedixTM in February of 2018 (NCT03466216); the study is currently recruiting patients at the Excel Diagnostics and Nuclear Oncology Center in Houston, TX U.S.

"FDA’s decision to grant Orphan drug Designation is an important regulatory milestone for AlphaMedixTM, a key program in our pipeline of 212Pb-labeled compounds," said Julien Dodet, CEO of Orano Med. "We believe TAT with 212Pb represents a promising new approach and that AlphaMedixTM has the potential to have a meaningful impact on patients".

Orphan designation is granted by the FDA Office of Orphan Products Development to advance the evaluation and development of safe and effective therapies for the treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. The designation provides certain benefits to drug developers such as seven-year marketing exclusivity upon FDA approval, tax credits for qualified clinical testing or prescription drug user fee exemption.

About Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms that originate from neuroendocrine cells. These neoplasms occur mostly in the gastrointestinal tract and pancreas, but can also occur in other tissues including thymus, lung, and other uncommon sites such as ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors (SSTRs).

About AlphaMedixTM

AlphaMedixTM is a radiolabeled SSTR-targeting therapeutic investigational drug for the treatment of NETs patients. The product consists of SSTR-targeting peptide complex radiolabeled with 212Pb and serve as an in vivo generator of alpha-emitting particles. 212Pb isotope is particularly suitable for SSTR therapy applications based upon its half-life, energy and decay properties.

On November 13, 2018 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported its results for the third quarter 2018 (Press release, BerGenBio, NOV 13, 2018, View Source [SID1234531234]). A presentation of the results by the Company’s management will take place today at 10.00 am CET in Oslo – details below.

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Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We are pleased with the progress of our phase II clinical development programme with our selective AXL inhibitor bemcentinib, particularly in NSCLC. The observed correlation between patient response and positive AXL status in our combination trial with KEYTRUDA gives us confidence in bemcentinib’s proposed mode of action and its broad appeal as a promising new agent treating aggressive cancer. The next six to nine months will be an exciting time for the company as we anticipate further clinical data from our phase II trials, particularly in NSCLC and acute myeloid leukaemia."

Highlights – Third Quarter & 2018
Bemcentinib/KEYTRUDA combination in advanced non-small cell lung cancer (NSCLC) delivers highly promising phase II clinical results

40% overall response rate & 70% clinical benefit rate observed in AXL-positive, previously treated NSCLC patients, including PD-L1 negative patients (data presented at World Conference on Lung Cancer (WCLC))
5.9 months median progression-free-survival (PFS) in AXL positive vs. 3.3 months in AXL negative patients presented as late breaking abstract at Society Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) congress (SITC, post-period)
Efficacy endpoint met and stage two of the trial actively enrolling
Additional lung cancer phase II trials show promise for bemcentinib in combination with chemo- and targeted agents

Median PFS of NSCLC patients receiving the bemcentinib/TARCEVA combination in first line has surpassed that of TARCEVA monotherapy (data presented at WCLC)
Encouraging efficacy reported for bemcentinib in combination with docetaxel chemotherapy in patients who had exhausted all available therapy options (data presented at WCLC)
Tissue- and blood-based biomarkers with potential for development as companion diagnostics

Novel biomarkers identified and qualified across multiple clinical trials with bemcentinib, presented as poster discussion at European
Society for Medical Oncology meeting (ESMO) (Free ESMO Whitepaper) and SITC (Free SITC Whitepaper) 2018 (post period)
Arbitration process with Rigel Pharma Inc.

The Company is seeking clarification of interpretation and application of certain provisions of the 2011 bemcentinib license agreement
Anticipated data and news flow in the coming months

AML and MDS mono- and combination therapy at ASH (Free ASH Whitepaper) 2018
Stage 2 of bemcentinib/KEYTRUDA combination trial in H1 2019
IND filed for BGB149, first in class AXL function blocking antibody (post period)
Financial Highlights (Figures in brackets = same period 2017 unless otherwise stated)

Total operating expenses for the third quarter were NOK 38.1 million (NOK 36.6 million). Total operating expenses for the first nine months of 2018 amounted to NOK 143.6 million (NOK 136.2 million)
Research and development expenses accounted for 75.3 % of total operating expenses in Q3, and 72.3 % for the first nine months of 2018
Comprehensive loss for the third quarter amounted to NOK 37.7 million (loss of NOK 35.4 million). Comprehensive loss for the first nine months of 2018 was NOK 140.7 million (loss of NOK 134.6 million)
Cash and cash equivalents amounted to NOK 398.2 million at the end of September 2018 (NOK 440.3 million at 30 June 2018 and NOK 370.3 million at 31 December 2017)
Presentation and Webcast Details

A presentation by BerGenBio’s senior management team will take place at 10.00 am CET at:

Hotel Continental, Stortingsgaten 24/26, 0117 Oslo

The presentation will webcast live and the link will be available at www.bergenbio.com in the section Investors/ Financial Reports. A recording will be available shortly after the webcast has finished.

The results report and the presentation will be available at www.bergenbio.com in the section: Investors/ Financial Reports from 7:00 am CET the same day.

END

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms that drive aggressive and life-threatening diseases. In cancer, AXL drives tumour survival, treatment resistance and spread, as well as suppressing the body’s immune response to tumours. AXL expression has been established as a negative prognostic factor in many cancers. AXL inhibitors, therefore, have potential value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities

On November 13, 2018 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq:YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported financial results for the third quarter of 2018 (Press release, Y-mAbs Therapeutics, NOV 13, 2018, View Source [SID1234531251]).

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"We are very pleased to report our first quarterly financials after Y-mAbs’ successful IPO in September, which have put us in a strong financial position to continue the important work on our two lead pediatric compounds, naxitamab and omburtamab. We plan to file BLAs for both of these compounds next year." stated Thomas Gad, Founder, President and Head of Business Development and Strategy.

Dr. Moller, Chief Executive Officer continued, "We have made solid progress with naxitamab and omburtamab in the clinic in recent months. Over the remainder of 2018, we have much to do and also numerous catalysts that have the potential to solidify us as a leader in pediatric oncology and a company focused on rapidly developing therapies to extend and enhance the lives of those living with rare pediatrics cancers."

Third Quarter 2018 and Recent Corporate Developments

After the close of the quarter, on November 1, 2018, Y-mAbs announced that that Dr. Jeong A Park from the Department of Pediatrics of Memorial Sloan-Kettering Cancer Center (MSK) will present preclinical data from the Company’s bispecific GD2 antibody in a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 3, 2018, at 9:00 PM Eastern. Bispecific GD2 antibodies were tested in solid tumors in preclinical models with T-cells and were shown to exert anti-tumor effect against GD2(+) tumor xenografts or PDX tumors. Further, the bispecific GD2 antibodies induced rapid and quantitative T-cell homing to tumors, mediating antibody dependent T-cell mediated cytotoxicity (ADTC) against GD2, and were shown to infiltrate tumors with little to no immune response, also known as cold tumors.

After the close of the quarter, on October 23, 2018, Y-mAbs announced that the Committee for Orphan Medicinal Products of the European Medicines Agency recommended the granting of orphan medicinal product designation in the European Union for naxitamab for the treatment of relapsed or refractory high-risk neuroblastoma. Further, the positive opinion for orphan medicinal product designation had been sent to the European Commission, which may grant the orphan drug designation within 30 days thereof.

On September 25, 2018, Y-mAbs announced the closing of its initial public offering of 6,900,000 shares of its common stock, including the exercise in full of the underwriters’ option to purchase 900,000 additional shares of common stock, at a public offering price of $16.00 per share. The gross proceeds to Y-mAbs, before deducting underwriting discounts and commissions and estimated offering expenses payable by the Company, were approximately $110.4 million. All of the shares of common stock were offered by the Company, and Y-mAbs’ common stock is listed on The Nasdaq Global Select Market under the ticker symbol "YMAB."

On August 21, 2018, Y-mAbs announced that it had received Breakthrough Therapy designation for naxitamab, in combination with GM-CSF, for the treatment of high risk neuroblastoma refractory to initial therapy or with incomplete response to salvage therapy in patients older than 12 months of age with persistent, refractory disease limited to bone marrow with or without evidence of concurrent bone involvement.
Financial Results

Y-mAbs reported a net loss of $11.4 million or $0.42 per basic and diluted share for the third quarter of 2018 compared to a net loss of $3.8 million or $0.21 per basic and diluted share for the third quarter of 2017.

For the nine months ended September 30, 2018, Y-mAbs reported a net loss of $29.2 million, or $1.08 per basic and diluted share, compared to a net loss of $9.9 million reported for the same period of 2017, or $0.56 per basic and diluted share.

Cost and Operating Expenses

Research and development
Research and development expenses were $8.7 million for the third quarter of 2018, compared to $3.1 million for the same period of 2017, an increase of $5.6 million. The increase in research and development expenses primarily reflects the following:

$3.4 million increase in outsourced manufacturing for our lead product candidates, naxitamab and omburtamab
$1.3 million increase in outsourced research and supplies to support expanding development activities
$0.7 million increase in personnel costs
Research and development expenses were $23.2 million for the nine months ended September 30, 2018, compared to $7.7 million for the same period of 2017, an increase of $15.5 million. The increase in research and development expenses primarily reflects the following:

$6.4 million increase in outsourced manufacturing for our lead product candidates, naxitamab and omburtamab
$3.5 million increase in outsourced research and supplies to support expanding development activities
$2.1 million increase in clinical trial costs due to an increasing number of ongoing clinical trials
$2.4 million increase in personnel costs
$0.6 million increase in milestone payments
General and administration

General and administrative expenses were $2.7 million for the third quarter of 2018, compared to $0.8 million for the same period of 2017, an increase of $1.9 million. The increase in general and administrative expenses primarily reflects the following:

$1.1 million increase in personnel costs
$0.5 million increase in fees for auditors, legal advice and other consultancy services
General and administrative expenses were $5.9 million for the nine months ended September 30, 2018, compared to $2.3 million for the same period of 2017, an increase of $3.6 million. The increase in general and administrative expenses primarily reflects the following:

$1.4 million increase in personnel costs
$1.3 million increase in fees for auditors, legal advice and other consultancy services
Cash, Cash Equivalents, Investments and Restricted Investments

The Company had approximately $163.3 million in cash and cash equivalents as of September 30, 2018 compared to $90.5 million as of December 31, 2017. The increase is primarily driven by the $100.5 million net proceeds from the Company’s initial public offering, which is partly offset by the use of cash to fund the Company’s ongoing operations during the first three quarters of 2018.

On November 13, 2018 OncoSec Medical Inc., (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported that TAVO will be featured in two poster sessions during the 2018 San Antonio Breast Cancer Symposium (SABCS) taking place December 4-8 in San Antonio, Texas (Press release, OncoSec Medical, NOV 13, 2018, View Source [SID1234531329]). Posters include data on TAVO as a monotherapy and an initial project overview for KEYNOTE-890, a Phase 2 clinical trial in combination with Merck’s KEYTRUDA (pembrolizumab) for the treatment of late stage triple negative breast cancer (TNBC).

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"We are encouraged with the preliminary clinical observations we are seeing thus far, both in a monotherapy setting and in combination with checkpoint inhibitors," said Daniel J. O’Connor, President and Chief Executive Officer of OncoSec. "Based on this, we are excited to continue on the path toward developing novel treatment options for this large unmet medical need,"

Details on the poster presentations are as follows:

Presentation Title: Intratumoral tavokinogene telseplasmid and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer
Session Date & Time: Thursday, December 6, 7:00 – 9:00 a.m. CT (8:00 – 10:00 a.m. ET)
Session Title: Poster Session 2: Treatment: Immunotherapy (clinical)
Location: Hall 1, Henry B. Gonzalez Convention Center

Presentation Title: A phase 2 study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation with pembrolizumab in patients with inoperable locally advanced or metastatic triple negative breast cancer
Session Date & Time: Thursday, December 6, 5:00 – 7:00 p.m. CT (6:00 – 8:00 p.m. ET)
Session Title: Ongoing Clinical Trials: Immunotherapy
Location: Hall 1, Henry B. Gonzalez Convention Center

The abstracts for these presentations are now available online on the SABCS website at View Source

On November 13 2018 FUJIFILM Corporation (President: Kenji Sukeno) reported that it has succeeded in stably encapsulating the anti-cancer agent topotecan*, approved for the treatment of several solid cancers, in newly invented liposome (Press release, Fujifilm, NOV 13, 2018, View Source [SID1234538525]). When preclinical studies in mice were conducted using a drug where topotecan was encapsulated in liposomes (development number: FF-10850), in addition to confirming high tumor shrinking effects, improved pharmacological efficacy was demonstrated when administered in combination with an immune checkpoint inhibitor**, with prolonged survival compared to monotherapy. Going forward, based on the results of these nonclinical studies, the company will prepare for the early initiation of clinical studies of the drug candidate.

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Fujifilm conducts research and development on the potential use of encapsulating drugs in liposomes, artificially constructed vesicles made from organic phospholipids that make up cellular membranes, by harnessing its advanced nano-dispersion technology, analysis technology, and process technology cultivated through its wide range of product development. In another study the liposome drug candidate FF-10832, which encapsulates the anti-cancer agent gemcitabine*** , has been observed to protect gemcitabine from elimination and demonstrate an enhanced permeability and retention (EPR) effect*4 by which the FF-10850 accumulates within tumor and releases gemcitabine. A Phase I clinical trial of FF-10832 is underway in the U.S.
Topotecan has an extremely short half-life*5 in the blood, and also has the issue of causing serious bone marrow suppression*6 as a side effect in more than 80% of patients. A liposome drug where topotecan is encapsulated can be considered as a way to resolve these issues; however, topotecan has a tendency to pass through the liposome membrane, resulting in a problem where topotecan would leak into the blood before reaching the tumor. By enhancing the strength of the liposome membrane with the addition of new materials to the liposome ingredients, Fujifilm has succeeded in stably encupsulating topotecan. Fujifilm is conducting research on the drug as a candidate anti-cancer agent (development number: FF-10850), and has obtained the following results in studies in mice.

[Research Result 1] High tumor shrinking effects confirmed with monotherapy

1) Experiment:
Mice with transplanted human-derived ovarian cancer cells (ES-2) were administered with topotecan and FF-10850, respectively, and the efficacy and tolerability were confirmed for each dosage. The period of administration was five consecutive days for topotecan and two cycles of one administration per week for FF-10850.
2) Results:
With topotecan, efficacy was observed with 30 mg/m2 (6 mg/m2 x five times), while with FF-10850, efficacy was confirmed with 3 mg/m2 (1.5 mg/m2 x twice). When the two drugs were compared, FF-10850 demonstrated efficacy that was greater than or equal to topotecan with 1/10 of the total dose of topotecan.
With FF-10850, tumor shrinking effects were seen with 8 mg/m2 (4 mg/m2 x twice). Furthermore, the relative body weight change which is an indicator of tolerability, was less than that of topotecan.
[Chart] Tumor volume and relative body weight change upon administration of FF-10850 and topotecan
Based on the above, FF-10850 is expected to have high pharmacological efficacy that exceeds that of topotecan while maintaining tolerability even when dosage is increased.

[Research Result 2] Improved pharmacological efficacy observed when administered in combination with an immune checkpoint inhibitor

1) Experiment:
Monotherapies and combination therapy with an immune checkpoint inhibitor** and FF-10850 was conducted on mice transplanted with mouse-derived colorectal cancer cells (CT26), and efficacy and tolerability were confirmed. The period of administration was three cycles of two administrations per week for the immune checkpoint inhibitor (30 mg/m2) and three cycles of one administration per week for FF-10850 (6 mg/m2).
2) Results:
When administered as a monotherapy, the median value for mouse survival time was 19 days for the immune checkpoint inhibitor and 27.5 days for FF-10850. Meanwhile, when administered as a combination therapy, the median value for mouse survival time exceeded 40 days, demonstrating a statistically significant difference when compared with the monotherapies. Mouse survival rates for the combination therapy were 75% at 40 days after administration, which was higher than the monotherapies.
Even when administered as a combination therapy, noticeable side effects such as weight loss were not observed, and there were no issues with tolerability.
[Chart] Survival rates and median survival time when administered in combination with an immune checkpoint inhibitor
Based on the above, FF-10850 is expected to further suppress tumor proliferation through administration with an immune checkpoint inhibitor and prolong survival time.

Fujifilm will present its research results on FF-10850 at the "30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) SYMPOSIUM", one of the world’s most prominent cancer related conferences, to be held in Dublin, Ireland from November 13th to 16th, 2018.

Fujifilm is harnessing its advanced technologies such as the nano-dispersion technology and ability to synthesize and design compounds to undertake the development of new drugs in the key areas of cancer, central nervous system diseases, and infectious diseases. The company is also focusing on developing drug delivery system (DDS) technologies including liposome drugs, undertaking research and development to apply DDS technologies not only to low-molecular-weight drugs but also to next-generation drugs such as nucleic acid drugs and gene therapy drugs. Going forward, the company will contribute to the resolution of social issues by developing and delivering innovative, high value-added pharmaceutical products.

* An anti-cancer agent (generic name: topotecan, product name: Hycamtin) developed by GlaxoSmithKline plc. Currently, the drug is distributed by Novartis. It is used as a treatment for ovarian cancer, small-cell lung cancer, and cervical cancer.
** The general term for drugs that have an effect by enabling activated immune cells to attack cancer cells by inhibiting the mechanism (immune checkpoints) that weakens the action of immune cells. Widely used in the treatment of malignant melanomas, lung cancer, stomach cancer, and kidney cancer. The immune checkpoint inhibitor used in the combination therapy with FF-10850 was an anti-PD-1 antibody.
*** An anti-cancer drug (generic name: gemcitabine, product name: Gemzar) developed by the U.S. company Eli Lilly and Company. It is used as a drug of first choice for the treatment of pancreatic cancer, and is also indicated for the treatment of a wide range of other cancers (such as lung cancer and ovarian cancer).
*4 As they grow, tumors generate surrounding blood vessels, but these newly generated blood vessels are not fully developed and have large gaps that are much smaller in normal blood vessels. When liposomes and polymers are retained within the blood, they do not permeate the walls of normal blood vessels, which have small gaps, permeating only the vascular walls around the tumor. In addition, as lymphatic vessels are not fully developed in tumors, the liposomes and polymers that have permeated are not easily eliminated, resulting in the accumulation of these liposomes and polymers in the tumor. This is called the EPR (enhanced permeability and retention) effect.
*5 The time required for the concentration of a drug in the blood to be reduced to half.
*6 The state where production of white blood cells, platelets, and red blood cells in the bone marrow is reduced, leading to increased risk of infection and bleeding and symptoms such as anemia.