Adamis Pharmaceuticals Announces 2018 Financial Results and Provides Business Update

On March 15, 2019 Adamis Pharmaceuticals Corporation (NASDAQ: ADMP) reported financial results for the year ended December 31, 2018 and provided a business update (Press release, Adamis Pharmaceuticals, MAR 15, 2019, View Source [SID1234534400]).

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Dr. Dennis J. Carlo, President and Chief Executive Officer of Adamis Pharmaceuticals, stated, "There were several significant developments for our company during 2018. I view the marketing and distribution agreement with Sandoz for our SYMJEPI products, approval of the SYMJEPI 0.15mg product and submission of a new drug application (NDA) for our higher dose naloxone injection product to be the most significant developments, laying the groundwork for what I hope will be a transformative year for the company. We are also encouraged by the performance of US Compounding in early 2019 and we look forward to expanding our production capacity."

Select Events Since Last Business Update:

First commercial product delivered to Sandoz;

NDA submitted to the FDA and accepted for review for the higher dose naloxone injection product candidate;

NDA submitted to the FDA and received a refusal to file letter for the tadalafil product candidate;

Drug Outsourcing Facility (U.S. Compounding) increased revenue by 15%; and

Sandoz announces launch of SYMJEPI 0.3mg product to the institutional market in the U.S.
Product Updates

SYMJEPI (epinephrine) Injection (0.3mg and 0.15mg)

As announced in the third quarter of 2018, the company entered into a commercialization and distribution agreement with Sandoz, a division of Novartis, to market and sell SYMJEPI (epinephrine) Injection 0.3mg and SYMJEPI (epinephrine) Injection 0.15mg (upon approval) in the U.S. The company also granted Sandoz a right of first negotiation for territories outside the U.S. On September 27, 2018, the FDA approved the SYMJEPI 0.15mg product. In January 2019, Sandoz announced the launch of SYMJEPI 0.3mg product for the institutional market in the U.S.

APC-6000 (naloxone)

As announced in December 2018, the company filed an NDA relating to its higher dose naloxone injection product for the treatment of opioid overdose. On March 14, 2019, the company received notice from the FDA that it had determined the NDA was sufficiently complete to permit a substantive review and provided a target agency action date of October 31, 2019. Please refer to the company’s March 14, 2019 press release for additional information.

APC-8000 (sublingual tadalafil)

In December 2018, the company announced that it had filed an NDA for a fast-disintegrating sublingual tadalafil (APC-8000) product candidate. On February 26, 2019, the company received a refusal to file letter from the FDA indicating it had determined that the submitted NDA was not sufficiently complete to permit a substantive review. The FDA requested that the company supplement and include in a resubmitted NDA additional data and information. The company continues to evaluate the FDA’s comments, and it may seek immediate guidance from the FDA, including requesting a Type A meeting, to discuss the letter and the specific deliverables the agency would require for a resubmitted NDA to be deemed complete.

APC-1000 (beclomethasone)

In 2018, the company submitted an IND application and received clearance from the FDA to begin Phase 3 efficacy studies for APC-1000. In Q4 2018, it initiated the start-up phase of the phase 3 studies of APC-1000. The company anticipates that trial enrollment will commence in 2019; however, the timing of enrollment and completion of such studies could be affected by a number of factors as described in the company’s Form 10-K.

APC-4000 (fluticasone)

During 2018, the company completed development and manufacturing work on the patented dry powder inhaler (DPI) technology that the company acquired from 3M. Adamis is now focused on continuing and completing the drug development work, which includes loading fluticasone onto the tape and into the device, in order to demonstrate the device can achieve the targeted dosing. Once completed, the company may seek a development or commercial partner to help advance the product through a regulatory pathway.

Drug Outsourcing Facility

The company’s wholly-owned subsidiary, US Compounding (USC), has continually grown its revenues year over year since Adamis acquired the division. During 2018, USC continued to make improvements in its processes and efficiencies while maintaining its focus on quality. Although net revenue grew 15% over 2017, it did not meet the company’s previously stated growth target. Therefore, during the first quarter of 2019, Adamis has made changes to USC personnel and strategy with the objective of achieving profitability for the division during 2019.

2018 Financial Results

Revenues were approximately $15.1 million and $13.1 million for the years ended December 31, 2018 and 2017, respectively. The increase of approximately $2.0 million reflected an increase in sales of USC’s compounded and non-compounded pharmaceutical formulations resulting in part from price increases, increase in unit sales production capacity in order to meet product demand, and marketing personnel efforts.

Selling, general and administrative expenses (SG&A) for the years ending December 31, 2018 and 2017 were approximately $26.0 million and $22.8 million, respectively. SG&A expenses consist primarily of depreciation and amortization, legal fees, accounting and audit fees, professional/consulting fees and employee compensation. Compensation expense for SG&A employees increased by approximately $2.0 million for 2018 compared to 2017, primarily due to new hires, increases in salary expenses and bonus accruals, and expenses associated with equity compensation and other employee benefits. Approximately $0.5 million of the increase for 2018 was due to PDUFA fees, marketing, selling, insurance, consulting, outside services and travel expenses; approximately $0.3 million of the increase was due to increases in patent fees; and approximately $0.4 million of the increase was due to increases in occupancy costs, insurance, supplies, taxes, and other related expenses.

Research and development expenses (R&D) were approximately $18.8 million and $7.5 million for the years ended December 31, 2018 and 2017, respectively. The increase in R&D for 2018, compared to 2017 was primarily due to an increase of approximately $8.8 million in development costs of the company’s product candidates, including APC-1000, APC-4000, APC-6000 and APC-8000. Compensation for R&D employees, consulting, and other operating expenses increased by approximately $1.6 million for 2018 compared to 2017, primarily due to new hires and cash and equity compensation expenses. As noted in its November 2018 press release, the company experienced increased research and development expenses for the fourth quarter of 2018.

At December 31, 2018, the Company had cash and cash equivalents of $19.3 million.

Targeted Future Milestones

FDA approval for the higher dose naloxone product candidate – target agency action date of October 31, 2019;
Sandoz’s launch of the SYMJEPI 0.3mg and 0.15mg products for the U.S. retail market;
Commercial agreements for the naloxone product candidate and for the SYMJEPI 0.3mg and 0.15mg products outside of the U.S.; and
US Compounding reaching profitability in 2019 (targeted by mid-year).

Curis to Present at the 6th Annual OMI Summit on Hematologic Malignancies

On March 15, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that Dr. Robert E. Martell, Head of Research & Development, will present a pipeline update at Oncology Meeting Innovation’s (OMI’s) 6th Annual Summit on Hematologic Malignancies on Saturday, March 16th, 11:10 a.m. PDT at the Fairmont Château in Whistler, British Columbia, Canada (Press release, Curis, MAR 15, 2019, View Source [SID1234534396]).

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The slides of the presentation will be available on the Company’s website: www.curis.com on the same day at 9:00 am EDT.

Nanobiotix 2018 Annual Results

On March 15 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported its unaudited1 consolidated results for the fiscal year ended December 31, 2018 (Press release, Nanobiotix, MAR 15, 2019, View Source [SID1234534395]):

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• Major milestones achieved during the year:

o Positive Phase II/III results for NBTXR3 in patients with locally advanced Soft Tissue Sarcoma demonstrating clinical meaningful benefits versus standard of care

o Positive clinical update from Phase I Head and Neck and Phase I/II Liver cancers trials presented at major congresses o Completion of Phase I dose escalation in Head and Neck cancers

o Engaged major preclinical collaborations with highly respected U.S. cancer centers including the University of Texas MD Anderson Cancer Center, the Providence Cancer Institute and Weill Cornell Medicine

• Consolidated cash available of €36.2M at December 31, 2018 o Strengthened by the payment of a €16M first tranche pursuant to a €40M non-dilutive financing agreement established with the European Investment Bank in 2018

• Expenses in R&D proceeding as expected according to clinical development plan

Philippe Mauberna, Chief Financial Officer of Nanobiotix said: "2018 has been a major year for Nanobiotix, we made significant progress in the financial and clinical plan of the company. R&D expenses are linked to our development plan and the hiring of experts in key positions. We are delighted by the positive results in Soft Tissue Sarcoma Phase II/III and the encouraging update from Head and Neck and Liver cancers Phase I/II trials. Indeed, the support of the European Investment Bank strengthens our balance sheet, which allows us to move forward with our 2019 upcoming key milestones."

The unaudited1 consolidated financial statements for the fiscal year ended December 31, 2018 were approved by the executive board and reviewed by the supervisory board of the Company on March 15, 2019.

Financial Review (unaudited)12

Total Revenue in 2018 amounted to €3.5M vs. €3.7M in 2017, mainly due to:
o Revenues related to services provided mainly by the Company to its partner, PharmaEngine, pursuant to a commercial agreement, amounted to €116K in 2018 (vs. €252K in 2017); and
o Other revenues of €3,363K in 2018 (vs. €3,469K in 2017) mainly related to the Research Tax Credit (Crédit d’Impôt Recherche-CIR).

Total Operating expenses reached €33.5M in 2018 vs. €29.0M in 2017:

o R&D expenses (including share-based payments) in 2018 amounted to €20.9M (vs. €17.7M in 2017); the variance comes from an increase in operations (opening of the new production site, launch and extension of new studies) as well as the addition of highly-qualified staff;

o SG&A costs (including share-based payments) in 2018 were €12.7M (vs. €11.3M in 2017).

Total headcount on a consolidated basis reached 102 as of December 31, 2018 vs. 85 as of December 31, 2017, in line with the Company’s growth.

Net loss after tax amounts to €30.3M as of December 31, 2018 (vs. €26.1M loss as of December 31, 2017).
Cash available at December 31, 2018 amounted to €36.2M.————————————-Nanobiotix activities and achievements in 2018
Clinical
Positive Phase II/III results for NBTXR3 in patients with locally advanced Soft Tissue Sarcoma demonstrated clinical meaningful benefits versus standard of care Nanobiotix announced positive results from its Phase II/III clinical trial of NBTXR3 in patients with locally advanced soft tissue sarcoma. The trial achieved its primary endpoint with a pathological complete response rate. It also achieved its secondary endpoint in operability. NBTXR3 demonstrated clinical meaningful benefits for such patients versus standard of care. The data also showed that NBTXR3 was well tolerated. The randomized trial validated the first-in-class mode of action of NBTXR3.
These positive results were presented by Dr. Sylvie Bonvalot at the ESMO (Free ESMO Whitepaper) and ASTRO annual conferences.

Positive Update on Head and Neck cancers Phase I trial showing potential impact for survival Nanobiotix provided an update on the Head and Neck Phase I Trial with NBTXR3 data presented at ImmunoRad 2018. The Phase I Trial focus on elderly and frail patients ineligible for cisplatin or intolerant to cetuximab. The data show the potential impact on survival in this patient population.

Encouraging Data from Phase I/II Liver cancers trial Nanobiotix presented initial promising data from Phase I/II Liver trial evaluating NBTXR3 in liver cancers, including primary (Hepatocellular, HCC) and liver metastasis from other tumors at the American Society of Clinical Gastrointestinal annual meeting (ASCO GI). These positive results show that NBTXR3 was well tolerated with no adverse event related to NBTXR3 and no dose-limiting toxicity.

Collaboration in preclinical research
Collaboration with the Providence Cancer Institute Nanobiotix partnered with the Providence Cancer Institute to run immunotherapeutic preclinical research in pancreatic 21 The Company’s statutory auditors have completed their audit work on the 2018 financial statements and expect to issue their audit report on March 20th, 2019. 3 cancer. This collaboration will provide essential preclinical data on the ability of NBTXR3 activated by radiotherapy to induce an antitumoral immune response.

The University of Texas MD Anderson Cancer Center and Nanobiotix have an agreement in pre-clinical research Nanobiotix and the University of Texas MD Anderson Cancer Center have an agreement to run immunotherapeutic preclinical research in lung cancer. The main objectives of this project, with one of the world’s leading oncology research centers, is to provide preclinical data using NBTXR3 activated by radiotherapy plus anti PD-1 Nivolumab (murine version of Opdivo).

Partnering with Weill Cornell Medicine on pre-clinical studies Nanobiotix and Weill Cornell Medicine partnered to perform pre-clinical studies to evaluate the impact of NBTXR3 on cGAS-STING pathway in mammary cancers. The main objective is to study the impact of NBTXR3 activated by radiotherapy on cGAS-STING, a key component of the anti-tumor immune response. Data generated from this collaboration could provide support for the assertion that NBTXR3 activated by radiotherapy can increase the antitumor immune response compared to radiotherapy alone.

Preclinical data showing NBTXR3 can activate cGAS-STING pathway Nanobiotix presented preclinical data showing NBTXR3 nanoparticles can activate the cGAS-STING pathway at the American Association for Cancer Research (AACR) (Free AACR Whitepaper). These observations support the rationale for using NBTXR3 with radiation therapy in combination with immunotherapeutic agents and/or STING agonist to transform tumors into an insitu cancer vaccine.

Financial events

Launch of a €40M non-dilutive financing agreement with the European Investment Bank Nanobiotix announced in July 2018, the launching of a non-dilutive financing agreement with the European Investment Bank to boost its research, development and innovation activities. This agreement will allow the Company to borrow up to €40M through loans before July 26, 2020 subject to achieving a set of agreed performance criteria. In October 2018, Nanobiotix received the first tranche disbursement of €16M. The proceeds will be used to speed up development of lead product NBTXR3 in Head and Neck cancers and to support the European go-to-market strategy.

Selection to the Euronext Tech 40

This honor recognizes the best performing Tech SMEs listed on Euronext markets. An independent group of European experts annually selects 40 great companies on the basis of their business, financial and stock market performance.

Events 2019

Large-scale collaboration on NBTXR3 with the University of Texas MD Anderson Cancer Center In January 2019, Nanobiotix and the University of Texas MD Anderson Cancer Center announced a large-scale comprehensive clinical collaboration on NBTXR3. The collaboration will initially support nine new Phase I/II clinical trials with NBTXR3 for use in treating six cancer types – head and neck, pancreatic, thoracic, lung, gastrointestinal and genitourinary cancers – and will involve around 340 patients. Most of the trials are expected to be launched in 2019. Nanobiotix will finance at least approximately $11M, a portion of which has been paid as of the start of the collaboration, with additional amounts payable during development and upon specified regulatory milestone.

Announced plans to conduct registered public offering in the US In January 2019, Nanobiotix announced that it plans to conduct a registered public offering of its ordinary shares, including the form of American Depositary Shares (ADSs) in the United States. Nanobiotix submitted a confidential draft registration statement on Form F-1 to the U.S. Securities and Exchange Commission.

Second tranche disbursement from the European Investment Bank In March 2019, Nanobiotix received the second tranche of disbursement of €14M from the European Investment Bank. This payment was granted because of the company’s achievement on two criteria: determination of the recommended dose at 22% of the tumor volume for head and neck cancers treatment following the end of Phase I clinical trial with NBTXR3 and positive evaluation of the clinical benefit/risk ratio of NBTXR3 in soft tissue sarcomas Phase II/III by the clinical expert mandated by the French medical device notified body, GMED. 4

2019 Perspectives

This year, Nanobiotix expects to receive its CE mark for NBTXR3 for the treatment of Soft Tissue Sarcoma, which would improve access to the product for cancer patients. In parallel, clinical development should advance with the publication of data in several cancer types.

Newsflow (anticipated)
-2019 – European market approval/CE mark for the treatment of Soft Tissue Sarcoma cancer
-1H2019–Preclinical data regarding immuno-oncology using NBTXR3 in combination with checkpoint inhibitors-1H2019–FDA feedback on NBTXR3 clinical plan in Head and Neck cancers
-2H2019 – Presentation of final Head & Neck Phase I dose escalation results
-2H2019–Potential early results in immuno-oncology with anti-PD-1 study-Multiple launches of clinical trials within MD Anderson collaboration-Additional news on other clinical trials and preclinical programs Additional news on plans to conduct registered public offering in the United States

Chugai Files a New Drug Application for a ROS1/TRK Inhibitor Entrectinib for the Treatment of ROS1 Fusion-Positive Non-Small Cell Lung Cancer

On March 15, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW) for a ROS1/TRK inhibitor entrectinib for the treatment of ROS1 fusion-positive non-small cell lung cancer (NSCLC) (Press release, Chugai, MAR 15, 2019, View Source [SID1234534393]).

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"With the previous filing of NTRK fusion-positive solid tumors, which is a rare type of cancer, and ROS1 fusion-positive NSCLC, which accounts for one to two percent of NSCLC, Chugai wishes that entrectinib would become a new treatment option for these patients and we will continue working to contribute to the development of personalized medicine," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit.

This application for approval is based on an integrated analysis of an open-label, multicenter, global phase II study (the STARTRK-2 study) and three overseas phase I studies (the STARTRK-NG study, the STARTRK-1 study and the ALKA-372-001 study). Efficacy was evaluated in 53 patients with ROS1 fusion-positive NSCLC while safety assessment was conducted with 355 patients registered in the four trials.

As the top pharmaceutical company in the field of oncology in Japan, Chugai will work to obtain early approval in order to provide entrectinib as a new treatment option for patients and medical professionals.

[Reference information]

Media release issued by Roche on February 19, 2019
Title: FDA grants Priority Review to Roche’s personalised medicine entrectinib
View Source
Media release issued by Chugai on December 19, 2018
Title: Chugai Files a New Drug Application for a ROS1/TRK Inhibitor Entrectinib for the Treatment of NTRK Fusion-Positive Solid Tumors
View Source
Media release issued by Roche on September 24, 2018
Title: Roche’s investigational medicine entrectinib showed a durable response of more than two years in people with a specific type of lung cancer
View Source
About entrectinib
Entrectinib is an oral medicine in filling for approval for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and inhibit proliferation of cancer cells with ROS1 or NTRK gene fusions. FDA has granted priority review for entrectinib for the treatment of NTRK fusion-positive solid tumors and ROS1 fusion-positive NSCLC.

About ROS1 fusion-positive NSCLC
ROS1 fusion gene is an abnormal gene that can be formed by fusing the ROS1 gene and other genes (CD74, etc.) as a result of chromosomal translocation for some reason. The ROS1 fusion kinase made from ROS1 fusion gene is thought to promote cancer cell proliferation. ROS1 fusion gene is found in about one to two percent of non-small cell lung cancer, among which it is more expressed in adenocarcinoma.

Sutro Biopharma Initiates Phase I Clinical Trial of STRO-002 for the Treatment of Ovarian and Endometrial Cancers

On March 15, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO) reported that it has dosed the first patient in a Phase I study of STRO-002, an anti-folate receptor alpha (FoIRα) antibody-drug conjugate (ADC), in patients with ovarian and endometrial cancers (Press release, Sutro Biopharma, MAR 15, 2019, View Source [SID1234534392]). This is the second product candidate to be evaluated in clinical trials resulting from Sutro’s XpressCF+ technology platform.

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The study is a multi-center, open-label, dose-escalation with dose expansion Phase I trial evaluating the safety, tolerability and preliminary anti-tumor activity of STRO-002. The study plans to enroll up to 160 women with advanced relapsed and/or progressive ovarian, fallopian, primary peritoneal or endometrial cancer.

"Moving our second product candidate into human clinical trials is another momentous milestone in Sutro’s evolution from a technology platform company to a clinical stage company," said Sutro CEO Bill Newell. "Our goal is to ultimately help fill the unmet need for more targeted therapies for patients with ovarian and endometrial cancer and advancing STRO-002 into the clinic brings us one step closer to achieving this."

STRO-002 is designed to target FoIRα, a cell-surface protein highly expressed in ovarian cancer. In preclinical studies, STRO-002 demonstrated potent in vitro cytotoxicity in ovarian cancer cell lines and significantly inhibited tumor growth in multiple ovarian cancer xenograft models. In safety studies conducted in non-human primates, STRO-002 was well tolerated at clinically relevant doses. "Based on observations from pre-clinical studies, STRO-002 has the potential to overcome traditional dose-limiting factors in the clinical setting, including ocular toxicity, which is a vexing problem with some ADCs," said Sutro Chief Medical Officer, Arturo Molina, M.D.

Denise Uyar, M.D., Associate Professor of Gynecology Oncology at Medical College of Wisconsin, an investigator in the STRO-002 study added, "Sutro’s unique ADC has the potential to be another important therapeutic option for oncologists in treating patients with ovarian and endometrial cancer. We look forward to evaluating the next-generation of ADCs in this study."

The Phase I study will consist of two parts: dose-escalation followed by dose-expansion. In both parts of the study, STRO-002 will be dosed as an intravenous infusion on Day 1 of 21-day cycles. Additional information can be found at View Source

STRO-002 was developed using Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitates precision design and rapid empirical optimization of ADCs and other product candidates.