On November 6, 2019 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS; Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on allogeneic gene-edited CAR T-cells (UCART), reported its results for the three-month and nine-month periods ended September 30, 2019 (Press release, Cellectis, NOV 6, 2019, View Source [SID1234550544]).

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"The third quarter of 2019 has been essential for our execution strategy, as we achieved a series of important key milestones that enable us to move our proprietary allogeneic UCART product candidates into Phase 1 clinical trials," said Dr. André Choulika, Chairman and CEO, Cellectis. "We are pleased to announce the first patient dosing in our MELANI-01 clinical trial for UCARTCS1, our UCART product candidate in relapsed/refractory multiple myeloma. We are also building out our clinical leadership team with the core addition of oncology veteran Dr. Francisco Esteva, M.D., Ph.D., as VP, Clinical Development. Following Novartis’ acquisition of CellforCure, our first CMO partner, at the beginning of 2019, we strengthened our manufacturing capabilities with the addition of our new CMO partner, Lonza, in addition to our existing partner MolMed S.p.A., while we remain on track with the construction of our in-house manufacturing facilities SMART and IMPACT. With three partnered and three stand-alone clinical development programs ongoing in hematology, Cellectis continues to be best-positioned to find new cures for cancers leveraging its core proprietary technologies."

Cellectis will hold a conference call for investors on Thursday, November 7, 2019 at 8:00 AM EST / 2:00 PM CET. The call will discuss the Company’s third quarter results, as well as an update on business activities for the first nine months of 2019.

The live dial-in information for the conference call is:

US & Canada only: 877-407-3104

International: 201-493-6792

In addition, a replay of the call will be available until November 21, 2019 by calling 877-660-6853 (Toll Free US & Canada); 201-612-7415 (Toll Free International), Conference ID: 13688263

Third Quarter and First Nine Months 2019 Highlights

Wholly Owned Pipeline Updates

MELANI-01:The Phase 1 dose-escalation clinical trial for UCARTCS1 targeting relapsed/refractory multiple myeloma has dosed its first patient and officially commenced at the University of Texas MD Anderson Cancer Center (Texas, USA). The clinical trial is also enrolling at Hackensack University Medical Center (New Jersey, USA) and a third site is planned to open at Weill Cornell Medicine (New York, USA).
BALLI-01:The Phase 1 dose-escalation clinical trial for UCART22 targeting relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) is ready to enroll patients at the University of Texas MD Anderson Cancer Center (Texas, USA), The University of Chicago Medicine Comprehensive Cancer Center (Illinois, USA) and Weill Cornell Medicine (New York, USA)
AMELI-01: We obtained a new IND number from the FDA in July 2019 for a new production process for UCART123. We are currently initiating sites for the Phase 1 dose-escalation clinical trial targeting relapsed/refractory acute myeloid leukemia (AML) at Weill Cornell Medicine (New York, USA), the University of Texas MD Anderson Cancer Center (Texas, USA), H. Lee Moffitt Cancer Center (Florida, USA) and Dana Farber Cancer Institute (Massachusetts, USA).
Scientific Publications

In February 2019, we announced the publication of a study in The Journal of Biological Chemistry, identifying Granulocyte Macrophage Colony Stimulating Factor (GMCSF) secreted by Chimeric Antigen Receptor (CAR) T-cells as a key factor in promoting cytokine release syndrome (CRS). The report leverages these findings to elaborate on an innovative engineering strategy that potentially paves the way for developing safer UCART products.

This publication is significant because Cellectis’ engineering strategy could circumvent toxic side effects such as CRS and neurotoxicity, thereby aiming to develop safer, yet equally potent, UCART product candidates in an effort to improve patients’ safety and quality of life during treatment.

On July 8, 2019, we announced the publication of a study in BMC Biotechnology, a Springer Nature journal, which described and evaluated the development of the SWIFF-CAR, a CAR construct with an embedded on/off-switch, which enables tight control of the CAR surface presentation and subsequent cytolytic functions using a small molecule drug.

This publication represents a promising approach to further mitigate the potential toxicities that are associated with CAR T-cell administration in clinical settings and to improve the process of CAR T-cell production for specific target antigens.

New Appointment

Francisco Esteva, M.D., Ph.D., joined Cellectis as Vice President, Clinical Development. He is responsible for overseeing U.S. medical activities and works with the Clinical Operations team to supervise and ensure the safety of clinical trials. Dr. Esteva currently serves as Adjunct Professor at NYU School of Medicine. He was most recently Director of Breast Medical Oncology and Associate Director of Clinical Investigation at NYU Langone Health’s Perlmutter Cancer Center, and Professor of Medicine at NYU School of Medicine. Prior to this, he was Professor of Medicine (Oncology) at The University of Texas MD Anderson Cancer Center, where he developed a successful program in translational and clinical research focused on HER2 targeted therapy. His training included MD/PhD degrees from the University of Zaragoza (Spain), a Residency in Internal Medicine at Cooper University Hospital (Camden, NJ) and a Fellowship in Medical Oncology at Georgetown University Medical Center (Washington DC). Dr. Esteva is an international thought leader for innovation in cancer care and clinical research. He is an elected member of the American Society of Clinical Investigation and a Fellow of the American College of Physicians. His research and clinical achievements have contributed to the approval of life-saving therapies in breast cancer.

Manufacturing

In March 2019, Cellectis announced its lease agreement for an 82,000 square foot commercial-scale manufacturing facility, called IMPACT, which stands for "Innovative Manufacturing Plant for Allogeneic Cellular Therapies". This new site, located in Raleigh, North Carolina, is being designed to provide GMP manufacturing for clinical supplies and commercial manufacturing upon regulatory approval. The facility is planned to be operational by 2021.

In addition to IMPACT, Cellectis is building a 14,000 square foot manufacturing facility in Paris, France, named SMART, which stands for "Starting Material Realization for CAR-T Products". This facility is designed to produce Cellectis’ critical starting material supplies for UCART clinical studies and commercial products.

Following Novartis’ acquisition of CellforCure, our first CMO partner, at the beginning of 2019, Cellectis announced, in October 2019, its new cGMP Manufacturing Service Agreement with Lonza for implementing Cellectis’ manufacturing processes in a way that meets the highest quality and safety standards outlined by the FDA and European counterparts. This contract complements not only the Company’s in-house work that is planned for IMPACT and SMART projects, but also the efforts of MolMed, Cellectis’ other contract manufacturing partner.

Patents

Over 2019, Cellectis has been granted the highest number of patents since the Company’s inception in 1999, in particular patents relevant to UCART19 (Japan), UCART123 (Europe), UCARTCS1 (Europe), UCART33 (Europe), UCARTBCMA (USA), UCART Alemtuzumab resistant (USA, Japan), Drug Resistant UCART (Europe), TALEN technology (USA), Mega-TAL TCR (Europe and Japan).

Additional US patents have been granted with respect to Cellectis’ exclusive licenses on CAR CS1 (US 10,227,409 and US 10,358,494 from the Ohio State University) and 7th patent on the TALEN technology (US 10,358,494 from the University of Minnesota).

Partnered Pipeline Updates

UCART19/ALLO-501 product candidate, initially developed by Cellectis and exclusively licensed by Cellectis to Servier, is being clinically tested under a joint clinical development collaboration between Servier and Allogene Therapeutics. UCART19/ALLO-501 product candidate utilizes the TALEN gene-editing technology pioneered and owned by Cellectis. Allogene has exclusive rights to UCART19/ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries. The development of UCART19 product candidate for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL) is sponsored by Servier. The development of ALLO-501 product candidate for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) is sponsored by Allogene.

In April 2019, our licensee, Allogene presented preclinical data demonstrating the potential for allogeneic CAR-T therapy in renal cell carcinoma (RCC) at the 2019 AACR (Free AACR Whitepaper) annual meeting. CD70, which is expressed on both hematologic malignancies and solid tumors, may bridge the gap toward unlocking the potential of allogeneic CAR-T therapy in solid tumors. The anti-CD70 product candidate is licensed exclusively from Cellectis to Allogene. Allogene holds global development and commercial rights to the anti-CD70 product candidate.

Based on the terms of the agreement, Cellectis is entitled to receive a $5 million milestone payment associated with the initiation of the study of ALLO-715 product candidate, an allogeneic CAR-T therapy targeting B-cell maturation antigen (BCMA) in relapsed/refractory multiple myeloma. As a reminder, each of the 15 targets licensed to Allogene by Cellectis carries $185 million in pre-commercial development milestones per target as well as high single-digit royalties on worldwide sales payable to Cellectis.

Financial Results

The interim condensed consolidated financial statements of Cellectis, which consolidate the results of Calyxt, Inc. of which Cellectis is a 69.1% stockholder, have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").

We present certain financial metrics broken out between our two reportable segments – Therapeutics and Plants – in the appendices of this Q3 2019 and First Nine Months 2019 financial results press release.

Third Quarter and First Nine Months 2019 Financial Results

Cash: As of September 30, 2019, Cellectis, including Calyxt had $367 million in consolidated cash, cash equivalents, current financial assets and restricted cash of which $299 million are attributable to Cellectis on a stand-alone basis. This compares to (i) $401 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of June 30, 2019 of which $323 million was attributable to Cellectis on a stand-alone basis and (ii) $453 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of December 31, 2018, of which $358 million were attributable to Cellectis on a stand-alone basis. This net decrease of $86 million for the nine-month period ended September 30, 2019 primarily reflects $66 million in net cash flows used by operating activities, of which $42 million are attributable to Cellectis, and $10 million in acquisitions of property, plant and equipment. We believe that the cash, cash equivalents, current financial assets and restricted cash position of Calyxt will be sufficient to fund their operations to mid-2021 while Cellectis only as of September 30, 2019 will be sufficient to fund operations into 2022.

Revenues and Other Income: Consolidated revenues and other income were $10 million for the three months ended September 30, 2019 compared to $2 million for the three months ended September 30, 2018. Consolidated revenues and other income were $17 million for the nine months ended September 30, 2019 compared to $18 million for the nine months ended September 30, 2018. 79% of consolidated revenues and other income was attributable to Cellectis in the first nine months of 2019. This decrease of $1 million between the nine months ended September 30, 2019 and 2018 was mainly attributable to a decrease in recognition of upfront payments already received and R&D cost reimbursements in relation to our therapeutic collaborations, and other income. That was partially offset by a $5 million milestone associated with the initiation of the study of ALLO-715, which became payable and was recognized by Cellectis, and $3.3 million increase in Calyxt revenues due to higher sales volumes of its High Oleic Soybean Oil and High Oleic Soybean Meal.

R&D Expenses: Consolidated R&D expenses were $22 million for the three months ended September 30, 2019 compared to $19 million for the three months ended September 30, 2018. Consolidated R&D expenses were $62 million for the nine months ended September 30, 2019 compared to $55 million for the nine months ended September 30, 2018. 86% of consolidated R&D expenses was attributed to Cellectis in the first nine months of 2019. The $7 million increase between the nine months ended September 30, 2019 and 2018 was primarily attributed to higher employee expenses by $4 million, higher social charges on stock option grants by $1 million, higher purchases and external expenses by $3 million and higher other expenses by $4 million. This increase was partially offset by the reduction of non-cash stock-based compensation expenses by $5 million.

SG&A Expenses: Consolidated SG&A expenses were $11 million for the three months ended September 30, 2019 compared to $12 million for the three months ended September 30, 2018. Consolidated SG&A expenses were $34 million for the nine months ended September 30, 2019 compared to $37 million for the nine months ended September 30, 2018. 44% of consolidated SG&A expenses was attributed to Cellectis in the first nine months of 2019. The $3 million decrease between the nine months ended September 30, 2019 and 2018 was primarily attributed to the reduction of non-cash stock-based compensation expenses by $4 million and to lower purchases and external expenses by $1 million. This decrease was partially offset by higher employee expenses and higher social charges on stock option grants by $2 million.

Net Loss Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $16 million (or $0.38 per share) for the three months ended September 30, 2019, of which $9 million was attributed to Cellectis, compared to $23 million (or $0.54 per share) for the three months ended September 30, 2018, of which $18 million was attributed to Cellectis. The consolidated net loss attributable to Shareholders of Cellectis was $65 million (or $1.52 per share) for the nine months ended September 30, 2019, of which $46 million was attributed to Cellectis, compared to $55 million (or $1.38 per share) for the nine months ended September 30, 2018, of which $42 million was attributed to Cellectis. This $9 million increase in net loss between the first nine months of 2019 and the corresponding prior-year period 2018 was primarily driven by an increase in operating losses of $9 million, of which $8 million was attributed to Calyxt.

Adjusted Net Loss Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $10 million (or $0.23 per share) for the three months ended September 30, 2019, of which $4 million is attributed to Cellectis, compared to $15 million (or $0.36 per share) for the three months ended September 30, 2018, of which $12 million was attributed to Cellectis. The consolidated adjusted net loss attributable to shareholders of Cellectis was $48 million (or $1.12 per share) for the nine months ended September 30, 2019, of which $35 million is attributed to Cellectis, compared to $28 million (or $0.70 per share) for the nine months ended September 30, 2018, of which $19 million was attributed to Cellectis. Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.

We currently foresee focusing on our cash spending at Cellectis for the remainder of 2019 in the following areas:

Supporting the development of our deep pipeline of product candidates, including the manufacturing and clinical trials expenses of UCART123, UCART22 and UCARTCS1;
Building our state-of-the-art manufacturing capabilities (IMPACT and SMART); and
Strengthening our manufacturing and clinical departments, including hiring talented personnel.
Calyxt plans to focus its cash spending for the remainder of 2019 in the following areas:

Continuing to drive the commercialization of its High-Oleic Soybean products, including Calyno High-Oleic Soybean Oil and High-Oleic Soybean Meal;
Supporting its innovative products pipeline; and
Strengthening its commercial and general and administrative support.

On November 6, 2019 AstraZeneca reported it will establish centers for drug research and artificial intelligence development in China (Press release, Xconomy, NOV 6, 2019, View Source [SID1234550560]). The pharmaceutical giant has also set up a $1 billion fund to foster biotech innovation in that country.

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The move – which was announced at the China International Import Expo this week – will see the AstraZeneca found a global R&D center in Shanghai’s central Jing’an district. The company currently operates R&D centers at its Cambridge, UK, headquarters as well as at sites in Maryland and Sweden.

The new China facility will carry out R&D for innovative drugs, with the focus being on diseases that are prevalent in China. The site will bring AstraZeneca’s R&D headcount in China to 1,000 people.

According to AstraZeneca, the firm will seek collaborations with local companies for drugs developed at the center as well as legacy products. A spokesman declined to specify which therapy areas will be the focus of R&D activities. Instead, he says AstraZeneca is "open to working with others through this infrastructure to tackle the key unmet needs, whatever they may be."

He also says AstraZeneca has no plans to co-locate all China R&D facilities, adding "we see benefit in locating facilities across China; the new site will be a complement to existing facilities in Shanghai, and Wuxi [City]."

The AI centre—which will also be located in Shanghai—will focus on the development of systems that are relevant to the discovery, development and production of biopharmaceuticals. Again, part of the center’s role will be to help AstraZeneca partner with local startup technology companies.

AstraZeneca’s China announcements comes as other biopharma firms position themselves to sell more drugs in that country. Earlier Wednesday, Biogen (NASDAQ: BIIB) expanded a pact with Samsung Bioepis to include the commercialization of three inflammation biosimilars in China. And last week, Amgen (NASDAQ: AMGN) announced it would pay $2.7 billion for a 20.5 percent stake in Beijing-based drug developer BeiGene (NASDAQ: BGNE). The companies will work together to sell Amgen’s cancer drugs in China; BeiGene will also help to develop 20 cancer drugs in Amgen’s pipeline for the Chinese market.

AstraZeneca’s focus on China makes sense as the country is the company’s most important market after the US.
According to the firm’s first half, 2019 financial results, drug sales in China were $2.4 billion, a 27 percent increase over the same period last year, and 22 percent of total product sales. The US accounted for more than $3.6 billion of AstraZeneca’s revenue in the first half of this year.

In addition to the new R&D and AI centres, AstraZeneca said it would set up five regional headquarters in China in Beijing, Chengdu, Guangzhou and Hangzhou. The new facilities—and the commercial innovation centers to be set up at each site—will work with the commercial operation the firm set up in Wuxi in 2017.

AstraZeneca has also partnered with state-owned bank CCIC to set up a $1 billion fund to foster biotech innovation in China.

The Healthcare Industrial Fund is intended to support domestic companies and partners including those based in the Wuxi International Life Science Innovation Campus.

Additionally, AstraZeneca says, the fund will support international companies that are looking to set up R&D operations and or partnerships in China.

On November 5, 2019 Vaccibody AS, a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel cancer vaccines, reported strong preliminary data from the ongoing VB N-01 phase I/IIa clinical trial of the VB10.NEO neoantigen cancer vaccine. The data is from the first 16 patients assessed for safety after treatment with a VB10.NEO, and the first 14 patients assessed for clinical responses.

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Key highlights include:

• Clinical responses were observed after treatment start with VB10.NEO in 50% of all analysed patients across tumour types o Lesion size reductions of 10-100% or stabilization of prior progressing lesions.

o All four head and neck cancer (SCCHN) patients, the melanoma patient, the nonsmall cell lung cancer (NSCLC) patient and one of eight renal cancer (RCC) patients show a clinical response after starting VB10.NEO vaccinations.

• Clinical responses correlate with high quality neoepitopes and strong de novo CD8 positive neoepitope-specific T cell responses induced by VB10.NEO. 2

Prof. Dr. med. Jürgen Krauss, of the Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Germany, and coordinating investigator of the study, said: "I am very pleased with the progress of this clinical phase I/IIa for Vaccibody’s neoantigen cancer vaccine. The data indicate that VB10.NEO induces best in class neoepitope-specific immune responses and the clinical responses observed in the first patients are highly intriguing. Since we have not observed any safety concerns with this treatment so far, there is a very high interest to broaden the patient population exposed to this innovative treatment. We are highly committed to continue this exciting program and we hope this clinical trial will help pave the way for a novel class of new efficacious and safe treatment for cancer patients."

Agnete Fredriksen President and CSO of Vaccibody, commented:

"We are very excited to see a clinical response with a clear effect on both the size and the growth of the lesions in a high number of the first patients treated with VB10.NEO as early as 9 weeks after the first dose of VB10.NEO.

Since we enrolled patients that had been treated with checkpoint inhibitor therapies for at least 5 months before the first dose of VB10.NEO, we are confident that in the cases of actual reductions of lesion sizes this effect can be attributed to the vaccine since most responses to checkpoint inhibitors happens within the first 3-5 months. After this period, further reductions in lesions size are unexpected and lesions that progress usually continue to grow without further interventions. Also, the observation of a strong correlation between high quality neoepitopes in the vaccine and the strength of de novo CD8 neoepitope-specific immune responses that translate into clinical responses is very encouraging.

Importantly, this confirms the ability of Vaccibody’s vaccine delivery platform to generate strong CD8 T cell responses, critical for tumour killing. Importantly, responses were also observed in patients with low tumour mutational burden that progressed after long-term checkpoint inhibitor therapy."

Michael Engsig, CEO of Vaccibody, continued: "To our knowledge, this is the first time that a neoepitope cancer vaccine shows the ability to actually shrink tumours, even in heavily pre-treated patients with advanced or metastatic disease. Taken together, we are very encouraged to build on these findings and continue development of our neoantigen cancer vaccine program."

Results Before VB10.NEO vaccination, most patients had received multiple lines of prior anti-cancer therapy and had been treated with a checkpoint inhibitor (CPI) (nivolumab or pembrolizumab) for 5-32 months. All had stable disease or mixed progressive disease when enrolled into the study. Five patients were progressing between enrolment and first dose of VB10.NEO and one had a partial response, while the remaining patients were stable. Twelve of the 14 patients 3 continued treatment with a CPI during VB10.NEO treatment. A clinical response, defined as either >10% reduction in the target lesions (as identified at screening) or converting progressive lesions into stable lesions (<20% increase, up to 37 weeks follow-up) after starting VB10.NEO treatment, was observed in seven of the 14 patients (4 SCCHN, 1 melanoma, 1 NSCLC and 1 RCC). The strongest clinical responses were most often seen in the lesions that were used to select the neoepitopes. Eleven patients had low tumour mutational burden (TMB), two patients had medium TMB and one patient had high TMB. The top 20 neoepitopes predicted by Vaccibody’s proprietary NeoSELECTTM algorithm were selected for each of the fully personalized VB10.NEO neoantigen vaccines. Vaccibody’s proprietary DNA vaccine manufacturing process has so far yielded 100% manufacturing success with the top 20 selected neoepitopes for all patients.

One RCC patient who discontinued CPI and started immunosuppressive treatment prior to first dose of VB10.NEO was not included in the immunogenicity analyses. Immunogenicity to each individual neoepitope was assessed in eight patients after six vaccinations by in vitro prestimulated IFN-γ ELISpot. The breadth and the strength of neoepitope-specific T cell responses were increased with number of vaccinations. Patients showing a clinical response also had the strongest immune responses and the highest frequency of high quality neoepitopes. The safety data for the 16 patients who has received at least one dose of VB10.NEO shows that VB10.NEO is well tolerated. Most common adverse events attributable to the VB10.NEO treatment were injection-related hypertensive episodes and injection site reactions. Four patients with SCCHN were assessed, three with low TMB and one with medium TMB. Two patients had progressive disease, one had stable disease and one had partial response at start of VB10.NEO vaccination. The patients had been on CPI for 12-32 months before starting VB10.NEO treatment. Strong neoantigen-specific T cell responses were seen in the vast majority (60-90%) of the selected neoepitopes after VB10.NEO vaccination with up to 1000-fold increase. A clinical response was observed in all four SCCHN patients: In the patients who had progressed on CPI before starting VB10.NEO a stabilisation or reduction in the size of the target lesions were observed after starting VB10.NEO treatment. In patients with stable disease or partial response on CPI, a reduction in lesion size was observed after starting VB10.NEO treatment. If the patients had multiple target lesions, the strongest response was observed in the lesions used to select neoantigens for the vaccine. Eradication of tumour cells containing the mutations targeted by the vaccine was observed in a follow-up biopsy from one of the patients. One melanoma patient was assessed. The patient had high TMB and stable disease at start of VB10.NEO vaccination and the patient had been on CPI for 10 months before treatment with VB10.NEO vaccination. An increased neoantigen-specific T cell response was seen to 50% of the selected neoepitopes after VB10.NEO vaccination with the majority being de novo responses. A clinical response with lesion size reduction was observed in the patient. 4

One NSCLC patient was assessed. The patient had medium TMB and stable disease as best response during nine months of CPI treatment before start of vaccination. Disease progression was observed during vaccine manufacturing with the occurrence of a new lesion. A clinical response in the form of rapid reduction in the target lesion was observed nine weeks after the first VB10.NEO vaccination.

Eight patients with RCC were assessed for clinical response, all with low TMB. Two patients had progressive disease and six had stable disease at start of VB10.NEO vaccination. One patient was taken off CPI and started immunosuppressive therapy prior to the first dose of VB10.NEO. Limited clinical responses have been observed until data-cut off (up to 37 weeks after first VB10.NEO vaccination). Interestingly, only one of the RCC patients has had an increase of >20% in the sum of target lesions and none of the lesions used to select neoantigens for the vaccine has progressed (defined as >20% increase in size.) Correlating with the limited clinical responses, fewer high-quality epitopes and neoepitope-specific immune responses were observed.

The Poster The Poster (ID: P424) will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting Saturday, 9 November, 7:00 am-8:30 pm local time in National Harbor, Maryland. Vaccibody staff will be available during the poster session at SITC (Free SITC Whitepaper).

On November 5, 2019 CANbridge Pharmaceuticals Inc., a biopharmaceutical company developing innovative drug candidates to treat underserved medical conditions in China and other markets, reported that it received market approval from the Department of Health in Hong Kong for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early‑stage hormone receptor positive HER2-overexpressed/amplified breast cancer, and who completed adjuvant trastuzumab-based therapy less than one year ago (Press release, CANbridge Life Sciences, NOV 5, 2019, View Source [SID1234550317]). This is the first targeted therapy approved in the CANbridge oncology platform and the first NERLYNX approval in greater China. CANbridge acquired the exclusive NERLYNX development and commercial rights for China, Taiwan, Hong Kong and Macao in 2018, and submitted the NDA for NERLYNX to the National Medical Products Administration (NMPA) in China for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, last year.

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"The rapid and smooth advancement of NERLYNX through the Hong Kong regulatory process to market approval is a testament to the quality of our regulatory expertise, and the CANbridge commitment to bring new treatments to underserved patient populations in greater China," said James Xue, PhD, Founder, Chairman and CEO, CANbridge Pharmaceuticals. "With this first targeted therapy approved in our oncology platform, CANbridge is able to provide women in Hong Kong, with HER2-positive breast cancer at risk of recurrence, a new and vital treatment option shortly after it was approved in the West."

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Research has shown that trastuzumab treatment can reduce the risk of early-stage HER2-positive breast cancer returning after surgery. However, up to 25% of patients treated with trastuzumab experience recurrence. There were 4,391 reported new cases of all types of breast cancer in Hong Kong in 2017, according to a report released by the Hong Kong Registry, Hospital Authority. Of these, it is reasonable to assume that 20-25% could be HER2-positive.

About Neratinib

Neratinib is a potent irreversible tyrosine kinase inhibitor that inhibits tumor growth and metastasis through the blocking of the pan-HER family (HER1, HER2 and HER4) and downstream signal transduction. Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. Neratinib was also approved by the European Medical Agency (EMA) in September, 2018.

On November 5, 2019 OPKO Health, Inc. (NASDAQ: OPK) reported business highlights and financial results for the three months ended September 30, 2019 (Press release, Opko Health, NOV 5, 2019, View Source [SID1234550333]).

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Business Highlights

Somatrogon meets primary and key secondary endpoints in global Phase 3 trial: On October 21, OPKO and Pfizer announced that the global Phase 3 trial evaluating somatrogon dosed once weekly in pre-pubertal children with growth hormone deficiency met its primary endpoint of non-inferiority to GENOTROPIN (somatropin) injected daily, as measured by annual height velocity at 12 months. Key secondary endpoints including change in height standard deviation scores at six and 12 months, and change in height velocity at six months, were also higher in the somatrogon group.

RAYALDEE total prescriptions reported by IQVIA increased 83% in 3Q 2019 compared with 3Q 2018: Total prescriptions for the three months ended September 30, 2019 increased to approximately 14,600, compared with approximately 8,000 during the comparable period of 2018.

BioReference Laboratories continued to establish new alliances: During the third quarter BioReference Laboratories formed a strategic collaboration with SOMOS, New York City’s largest multicultural physician-led network, and was named the preferred provider for the IPA Association of America in laboratory services and, also, to assist with data analytics for member patients. These wins build upon successes earlier in the year, including selection as part of the preferred lab network with UnitedHealthcare and new in-network status with Humana.

JAMA Oncology published data from a GeneDx study addressing cancer risk estimates for gastric cancers in patients with gene variants of CDH1: Results indicated that the lifetime risk of gastric cancer for individuals with pathogenic variants in the CDH1 gene is significantly lower than previously described; the lifetime risk of gastric cancer associated with pathogenic CDH1 variants was 42% in men and 33% in women, compared to published estimates of 40-70% in men and 56-83% in women. These results allow for a more personalized risk assessment and better informed decision making for patients at risk for hereditary gastric cancer.

Pharmaceutical pipeline continues to advance:

The open-label Phase 2 trial for RAYALDEE in hemodialysis patients is progressing and initial data are expected in 1Q 2020.

The somatrogon registration study in Japanese pediatric GHD patients to assess pharmacokinetics and compare efficacy of weekly somatrogon to daily GENOTROPIN is on track for data readout in 2020.

Financial Highlights

Consolidated revenues for the third quarter of 2019 were $228.8 million, compared with $249.8 million for the comparable period of 2018. Revenue from services in the third quarter was $181.1 million, revenue from products was $26.2 million, including RAYALDEE net revenue of $7.4 million, and revenue from licensing and intellectual property was $21.5 million.

Operating expenses for the third quarter of 2019 were $267.8 million. This included R&D expenses of $30.0 million, principally for the completion of the pediatric Phase 3 study for our long-acting human growth hormone product and other ongoing clinical trials.

Accounting rules require marking strategic investments to market at the end of each quarter, which had a negative impact on the net loss for the third quarter of 2019 of $13.6 million, or $0.02 per share. The net loss for the third quarter of 2019, after giving effect to the decrease in market value of our strategic investments, was $62.0 million, or $0.11 per share, compared with a net loss of $27.7 million, or $0.05 per share, for the comparable period of 2018. The 2018 period’s net loss benefited from an $11.6 million income tax benefit primarily resulting from a change in state income tax rates during that period.

Cash, cash equivalents and marketable securities were $64.7 million as of September 30, 2019. Subsequent to the close of the third quarter, the Company raised gross proceeds of $75.0 million from an underwritten public offering of common stock.

CONFERENCE CALL & WEBCAST INFORMATION

OPKO’s senior management will provide a business update and discuss results in greater detail in a conference call and live audio webcast at 4:30 p.m. Eastern time today, Tuesday, November 5, 2019. The conference call dial-in and webcast information is as follows:
DOMESTIC DIAL-IN:

866-634-2258
INTERNATIONAL DIAL-IN:

330-863-3454
PASSCODE:

7270239
WEBCAST:

OPKO 3Q19 Results Conference Call
For those unable to participate in the live conference call or webcast, a replay will be available beginning approximately two hours after the close of the conference call. To access the replay, dial 855-859-2056 or 404-537-3406. The replay passcode is 7270239. The replay can be accessed for a period of time on OPKO’s website at OPKO 3Q19 Results Conference Call.