On March 14, 2019 March 14, 2019 (GLOBE NEWSWIRE) — Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its fourth-quarter and full-year 2018 financial results (Press release, Constellation Pharmaceuticals, MAR 14, 2019, View Source [SID1234534359]).

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"2019 is a year of data for Constellation, and our clinical programs are making significant progress and approaching important readouts," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals.

"We are excited by preliminary data from our first four patients from the MANIFEST clinical trial, each showing one or more of the following: conversion from transfusion dependence to transfusion independence, hemoglobin increases, improvements in bone marrow fibrosis scores, spleen reductions, and symptom improvements. These results taken together suggest that CPI-0610 may have disease-modifying effects in myelofibrosis patients. We plan to present an interim update of data from MANIFEST from approximately 18-20 evaluable patients at a medical meeting in the second quarter of 2019.

"We also plan to present Phase 1b data from the ProSTAR clinical trial of CPI-1205 in metastatic castration-resistant prostate cancer in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting on April 1. Enrollment is on track in the Phase 2 portion of the ProSTAR trial, and we expect to provide an interim update of data of the Phase 2 portion at a medical meeting in the second half of 2019," Mr. Raythatha continued.

"The Constellation team continues to work diligently toward becoming a late-stage oncology development company and bringing important new medicines to underserved cancer patients," Mr. Raythatha concluded.

Recent News

MANIFEST

Enrollment is on track in the MANIFEST clinical trial in myelofibrosis patients. The Company has now opened approximately 20 clinical trial sites in the U.S., Canada, and Europe. As of February 28, 2019, 28 patients had been enrolled in the second-line arms of MANIFEST. The Company plans to provide an update on approximately 18-20 evaluable patients with at least three months of data at a second quarter medical meeting.

Each of the first four patients in MANIFEST remains on study. As of the last data cutoff on December 10, 2018, the first two patients treated with a combination of CPI-0610 and ruxolitinib had been treated for over 16 months. The first two patients treated with CPI-0610 monotherapy had been treated for over 12 months. As previously reported, each of these four patients has shown a reduction in spleen volume and improved hemoglobin levels. One of the combination therapy patients was transfusion dependent before therapy and converted to being transfusion independent after CPI-0610 was added to the patient’s regimen. As of December 10, 2018, this patient had been free of transfusions for over 52 weeks. Additionally, bone marrow biopsies before and after treatment were analyzed for the first two evaluable patients on monotherapy, and both demonstrated a one-grade improvement in bone marrow fibrosis score as well as associated improvements in hemoglobin. Taken together, these results suggest that CPI-0610 may be improving bone marrow function in these ruxolitinib-resistant MF patients.

We believe CPI-0610 has the potential for a differentiated toxicity profile compared with other BET inhibitors. In a Phase 1 clinical trial, the Company showed that the dose-limiting toxicity for BET inhibitors of thrombocytopenia was reversible and non-cumulative for CPI-0610. In addition, preliminary data suggest that CPI-0610 may have a wider therapeutic window relative to some other BET inhibitors, based on their published data. The recommended Phase 2 dose of CPI-0610 in the MANIFEST study is 125 mg once daily, with titration allowed up to 225 mg once daily, which is the maximum tolerated dose.
ProSTAR

Constellation plans to provide an update of Phase 1b data for ProSTAR in a poster at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Atlanta on April 1.
The Phase 2 portion of the ProSTAR clinical trial continues to enroll patients in line with the Company’s plans. Constellation plans to present an interim update of data of the Phase 2 portion of ProSTAR at a medical meeting in the second half of 2019.
Constellation recently began dosing in heavily pretreated patients in a new arm of ProSTAR. Previously, a compassionate-use patient, who had experienced disease progression despite treatment with 12 agents (including abiraterone, enzalutamide, and chemotherapy) prior to CPI-1205, experienced an 80% reduction in PSA levels and evidence of tumor size reduction in the neck lymph nodes when treated with CPI-1205 in combination with enzalutamide. The new treatment arm will enroll up to 30 patients in a single arm of CPI-1205 in combination with enzalutamide in heavily pretreated patients.
Corporate

On February 20, Constellation announced that Dr. Scott Braunstein was appointed to the Board of Directors. Dr. Braunstein is also a member of the Audit Committee. Dr Braunstein has an impressive track record of helping emerging and established biopharmaceutical companies as an investor and a pharmaceutical executive.
On March 1, Jessica Christo was appointed Chief Product Development Officer. Ms. Christo brings to Constellation 25 years of product development experience in the biopharmaceutical industry in clinical operations, data management, program management, biostatistics, and related fields.
Fourth Quarter 2018 Financial Results

Cash and cash equivalents as of December 31, 2018 decreased 10.8% to $114.6 million compared to September 30, 2018, primarily due to operating expenses.
Research and development (R&D) expenses increased 65.4% year over year to $16.6 million in the fourth quarter of 2018 mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 118.3% year over year to $4.0 million in the fourth quarter of 2018, primarily due to costs related to building out the organization as the Company evolved from a preclinical-stage company to a multi-candidate clinical-stage company, as well as costs associated with operating as a public company.
The net loss attributable to common stockholders increased 17.5% year over year to $19.9 million mainly due to increases in G&A and R&D expenses, partly offset by the inclusion of unpaid cumulative dividends in 2017 that were waived in 2018. The net loss per share attributable to common stockholders decreased 95.6% to $0.77 per share for the fourth quarter of 2018 due to an increase in shares outstanding as a result of the initial public offering and conversion of the preferred stock to common stock.
Full-Year 2018 Financial Results

Research and development (R&D) expenses increased 49.5% year over year to $48.8 million in 2018 mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 92.8% year over year to $12.5 million in 2018, primarily due to costs related to building out the organization as the Company evolved from a preclinical-stage company to a multi-candidate clinical-stage company, as well as costs associated with operating as a public company.
The net loss attributable to common stockholders increased 11.5% year over year to $59.9 million mainly due to increases in G&A and R&D expenses, partly offset by the inclusion of unpaid cumulative dividends in 2017 that were waived in 2018. The net loss per share attributable to common stockholders decreased 91.1% to $5.00 per share for 2018 due to an increase in shares outstanding as a result of the initial public offering and conversion of the preferred stock to common stock.
Financial Guidance

We expect that our cash and cash equivalents as of December 31, 2018, will fund operating expenses and capital expenditure requirements into the second quarter of 2020.

Anticipated Milestones

The Company anticipates achieving the following milestones during 2019:

First Half 2019

Provide a data update from the Phase 1b portion of the ProSTAR trial for CPI-1205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting on April 1
Provide an interim update of data from the MANIFEST Phase 2 trial of CPI-0610 at a second-quarter 2019 medical meeting
Initiate a Phase 1 trial for CPI-0209
Second Half 2019

Provide an interim update of data from the Phase 2 portion of the ProSTAR trial for CPI-1205
Provide an additional data update from the MANIFEST trial for CPI-0610
Financial Results (Unaudited)

Constellation Pharmaceuticals, Inc.
Consolidated Statements of Operations and Comprehensive Loss
Years ended
December 31, Three months ended
December 31,
(In thousands, except share and per-share amounts) 2018 2017 2018 2017
Revenue $ — $ — $ — $ —
Operating expenses:
Research and development 48,769 32,617 16,626 10,053
General and administrative 12,475 6,471 4,006 1,835
Total operating expenses 61,244 39,088 20,632 11,888
Loss from operations (61,244 ) (39,088 ) (20,632 ) (11,888 )
Other income (expense):
Interest income 1,547 169 688 58
Interest expense (228 ) (901 ) — (102 )
Change in fair value of preferred stock tranche liability — 4,443 — —
Total other income (expense), net 1,319 3,711 688 (44 )
Net loss and comprehensive loss (59,925 ) (35,377 ) (19,944 ) (11,932 )
Cumulative dividends on convertible preferred stock — (18,390 ) — (5,048 )
Net loss attributable to common stockholders (59,925 ) (53,767 ) (19,944 ) (16,980 )
Net loss per share attributable to common stockholders, basic and diluted $ (5.00 ) $ (56.10 ) $ (0.77 ) $ (17.64 )
Weighted average common shares outstanding, basic and diluted 11,984,293 958,447 25,789,305 962,330


Constellation Pharmaceuticals, Inc.
Consolidated Balance Sheets
(In $ thousands) December 31,
2018 December 31,
2017
Cash and cash equivalents 114,592 16,404
Other current assets 2,711 1,318
Total assets 118,938 19,103
Current liabilities 14,660 11,131
Total liabilities 14,780 11,708
Convertible preferred stock — 173,228
Total stockholders’ equity (deficit) 104,158 (165,833 )
Note: Abbreviated financial statements; please refer to Form 10-K for more details, including explanatory notes.

On March 14, 2019 Targovax ASA (OSE: TRVX), a clinical stage biotechnology company developing immune activators to target hard-to-treat solid tumors, reported that it has granted a freedom-to-operate (FTO) license to Zelluna Immunotherapy for the development of mutant RAS T cell receptor (mutRAS TCRs) therapies (Press release, Targovax, MAR 14, 2019, View Source [SID1234554018]).

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Through the development of the TG neoantigen vaccine program, Targovax has established a significant patent portfolio and know-how in therapies targeting mutant RAS cancers. In addition to covering the TG vaccine program, these patents and know-how are also highly relevant in T cell therapy.

Zelluna Immunotherapy has built a portfolio of validated mutRAS TCRs isolated from long-term cancer survivors treated with first generation TG mutRAS vaccines. Targovax has agreed to out-license Targovax patents and know-how to Zelluna to enable the development of Zelluna’s mutRAS TCRs and create a stronger joint position in the mutRAS TCR field. In addition, the companies have signed a letter of intent to establish an R&D collaboration for the discovery and development of additional novel mutRAS TCR products.

Under the license agreement, Zelluna has been granted a global, non-exclusive license to relevant Targovax patents and know-how, for which Targovax will be compensated financially. The potential deal value amounts to NOK 100 million in milestones and annual fees, in addition to royalties on sales and sub-licensing revenues. Zelluna will retain full rights to, and freedom to operate (FTO) for, its portfolio of mutRAS TCRs and will be responsible for the development of these.

Øystein Soug, CEO of Targovax, said: "Our unique TG technology has already demonstrated a clinical benefit by generating immune responses to RAS driver mutations, and we remain committed to developing mutRAS vaccines in the currently underserved mutant RAS cancer indications. Additionally, we are confident that our proprietary technology and know-how has potential application in the parallel field of T cell therapy; itself a rapidly evolving novel class of immunotherapies. The intention of joining forces with Zelluna, will be strengthening the ability to develop a portfolio of mutRAS TCR products to be applied in T cell therapy, which will complement our TG vaccine development and further solidify Targovax’s strong position as the leader in mutRAS targeted immunotherapy".

On March 14, 2019 AstraZeneca will share pioneering research and development across its successful Oncology portfolio and extensive next-generation pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, USA, 29 March to 3 April 2019 (Press release, AstraZeneca, MAR 14, 2019, View Source [SID1234534328]).

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The new research will showcase AstraZeneca’s potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, taking the DNA Damage Response (DDR) pipeline beyond PARP inhibition. Additional highlights include new insights from the MYSTIC and TATTON trials for Imfinzi (durvalumab) and Tagrisso (osimertinib) in predicting response and addressing treatment resistance in lung cancer.

In total, data from 84 presentations will illustrate the progress of AstraZeneca’s Oncology pipeline, with 28 abstracts reporting new Immuno-Oncology (IO) data, 33 focused on complementary biological pathways exploring the DDR mechanism, and 20 on tumour drivers and resistance mechanisms.

José Baselga, Executive Vice President, Research & Development, Oncology, said: "AstraZeneca is continuing to strengthen its portfolio of innovative cancer medicines by exploring new indications and developing a pioneering next-generation pipeline. We will be sharing some of our latest research at the 2019 AACR (Free AACR Whitepaper) Annual Meeting, including 28 new molecular entities and six combinations, highlighting an exciting new phase of scientific discovery from our Oncology R&D."

IO pipeline explores new pathways to enhance immune response

Key data from AstraZeneca’s early-stage clinical and preclinical IO pipeline include potential new medicines targeting multiple pathways, providing insight into novel mechanisms to boost current immune response and modify the tumour microenvironment both alone and in combination with checkpoint inhibition.

Presentations will highlight AstraZeneca’s growing portfolio in small molecules and antisense oligonucleotides (ASOs) targeting immunosuppressive mechanisms in cancer, and the Company’s exploration of the adenosine pathway, which is increasingly recognised as critical to tumour suppression and represents a new frontier within IO.

Phase I and preclinical data demonstrating AZD4635, a small molecule A2AR antagonist, prevents adenosine-mediated immunosuppression. Early clinical activity has been observed with AZD4635 monotherapy or in combination with Imfinzi in patients with metastatic castration-resistant prostate cancer (Abstracts #LB-192/10, #CT026/21)
Preclinical research on the activity of ASO AZD8701 (ION-AZ7), showing that inhibiting FOXP3 may limit immunosuppressive functions and induce tumour regression (Abstract #2713)
Preclinical pharmacodynamic and mechanistic data illustrating how danvatirsen (AZD9150), a STAT3 ASO reverses immunosuppression to produce significant anti-tumour effects, both as monotherapy and in combination with anti-PDL1 (Abstract #3215/25)
Preclinical data for MEDI5083, a novel fusion protein which activates the CD40 pathway, indicating robust immune activation and anti-tumour activity (Abstract #1534/3)
Preclinical data for MEDI1191, a novel IL12-based treatment designed for injection directly into tumours, showing potential to drive anti-tumour response for patients with solid tumours both as monotherapy and in combination with anti-PDL1 (Abstract #5017/11)
Next wave of DDR targets

New research will showcase AstraZeneca’s DDR pipeline beyond PARP inhibition, including on the discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor (Abstract #DDT01-02). DNA-PK is critical in repairing DNA double strand breaks through the non-homologous end joining (NHEJ) pathway and has also been linked to the replication stress response (RSR), a type of DDR.

Additional new data will be shared on reversing PARP inhibitor resistance by targeting alternative DDR dependencies, like the RSR (Abstract #932).

Predicting response and addressing treatment resistance in lung cancer: new insights from MYSTIC and TATTON trials for Imfinzi and Tagrisso

Exploratory analyses of blood and tissue tumour mutational burden (TMB) from the Phase III MYSTIC trial assess TMB as a potential biomarker of survival in 1st-line use of Imfinzi with or without tremelimumab vs. chemotherapy in metastatic non-small cell lung cancer (NSCLC) (Abstract #CT074). The trial did not meet the primary endpoints, but Imfinzi monotherapy demonstrated clinical activity in the primary analysis. The MYSTIC trial provides the most comprehensive data set to date evaluating blood TMB and is the only Phase III randomised, controlled trial to demonstrate an association between high TMB and overall survival benefit with immunotherapy treatment. This new analysis will further evaluate the use of TMB as a potential biomarker predictive of survival benefit with IO treatment.

In addition, several abstracts will be presented from the TATTON Phase Ib trial testing the combination of Tagrisso with potential new medicines savolitinib or selumetinib in NSCLC patients who have progressed on prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment (Abstracts #CT032, #CT033, #CT034). The TATTON trial supports SAVANNAH, an ongoing Phase II clinical trial exploring the combination of Tagrisso and savolitinib to overcome MET-driven EGFR-TKI resistance following treatment with Tagrisso in EGFR-mutated (EGFRm) NSCLC. Characterisation of detection methods for identifying MET-driven EGFR-TKI resistance will be presented (Abstract #4897/20). TATTON will also inform the trial design of ORCHARD, a Phase II platform trial exploring potential new treatment options to address resistance mechanisms in patients with EGFRm NSCLC who have experienced disease progression following 1st-line treatment with Tagrisso.

Key AstraZeneca presentations at AACR (Free AACR Whitepaper) 2019

Lead author

Abstract title

Presentation details

Immuno-Oncology

Peters, S

Tumour mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a Phase 3 study of first-line durvalumab ± tremelimumab vs chemotherapy

Abstract #CT074

Session CTPL03 – Optimizing PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy: Dedicated to the Memory of Waun Ki Hong

Monday 1 April

10:30am-12:45pm

Marcus Auditorium- Bldg A-GWCC

Srinivasan, S

STAT3 ASO reverses immunosuppression and enhances cytotoxic cell function to enhance PDL1 blockade

Abstract #3215/25

Session PO.IM02.01 – Combination Immunotherapies 2

Tuesday 2 April

8:00am-12:00pm

Section 23

Barbon, CM

The A2AR antagonist AZD4635 prevents adenosine-mediated immunosuppression of CD103+ dendritic cells

Abstract #LB-192/10

Session LBPO.IM02 – Late-Breaking Research:
Immunology 2

Tuesday 2 April

8:00am-12:00pm

Section 42

Merchant, MS

Evidence of Immune Activation in the first-in-human Phase 1a dose escalation study of the Adenosine 2a Receptor Antagonist, AZD4635, in patients with advanced solid tumors

Abstract #CT026/21

Session PO.CT01 – Phase I Clinical Trials: Part 1

Sunday 31 March

1:00pm-5:00pm

Section 16

Sinclair, C

Discovery and characterization of AZD8701, a high affinity antisense oligonucleotide targeting FOXP3 to relieve immunosuppression in cancer

Abstract #2713

Session MS.IM02.01 – Rational Combinations of Immunotherapy

Monday 1 April

4:35pm-4:50pm

Room A411-Georgia World CC

Wang, Y

MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen presenting cells and promotes a robust anti-tumor immune response in a B16F10 murine tumor model

Abstract #1534/3

Session PO.IM02.17 – Therapeutic Antibodies 2

Monday 1 April

8:00am-12:00pm

Section 25

Luheshi, N

MEDI1191, a novel IL-12 mRNA therapy for intratumoral injection to promote TH1 transformation of the patient tumor microenvironment

Abstract #5017/11

Session PO.IM02.10 – Tumor Immune Microenvironment

Wednesday 3 April

8:00am-12:00pm

Section 25

DNA damage response

Goldberg, FW

Discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor

Abstract #DDT01-02

Session DDT01 – New Drugs on the Horizon: Part 1

Sunday 31 March

1:24pm-1:48pm

Room A305 – Georgia World CC

Cadogan, EB

AZD7648: A potent and selective inhibitor of DNA-PK with pharmacodynamic and monotherapy anti-tumour activity

Abstract #3505/16

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

Fok, J

AZD7648, a potent and selective inhibitor of DNA-PK, potentiates the activity of ionising radiation and doxorubicin in vitro and causes tumour regression in xenograft models

Abstract #3512/23

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

O’Connor, M

Reversing PARP inhibitor resistance by targeting the replication stress response

Abstract #932

Session MS.ET03.01 – Drug Resistance

Sunday 31 March

4:35pm-4:50pm

Room B304 – Georgia World CC

Tumour drivers and resistance

Yu, H

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT032

Session CTPL02 – Can the Challenge of NSCLC Resistance be MET or Will We Not MEK It?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Sequist, L

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT033

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Ramalingam, S

Osimertinib plus selumetinib for patients (pts) with EGFR-mutant (EGFRm) NSCLC following disease progression on an EGFR-TKI: results from the Phase Ib TATTON study

Abstract #CT034

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Hartmaier, RJ

Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study

Abstract #4897/20

Session PO.CL11.07 – Novel Strategies for Biomarker Identification and Use in Cancer 3

Wednesday 3 April

8:00am-12:00pm

Section 19

Liquid biopsies

Barrett, JC

Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Major Symposium: Regulatory Science and Policy

Session SYPOL07 – Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Tuesday 2 April

3:00pm-5:00pm

Room A402 – Georgia World CC

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On March 14, 2019 Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical company focused on developing and commercializing novel tetracyclines to treat serious and life-threatening conditions, reported financial results for the fourth quarter and year ended December 31, 2018, provided an overview of recent achievements, and highlighted key milestones for 2019 (Press release, Tetraphase, MAR 14, 2019, View Source [SID1234534362]).

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"We capped off 2018 with a strong finish, with the regulatory approvals of XERAVA (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI) in both the U.S. and Europe, followed by the commercial launch of XERAVA in the U.S. in mid-October," said Guy Macdonald, President and Chief Executive Officer of Tetraphase. "With the U.S. launch off to a solid start, XERAVA is now available for use in U.S. hospitals and healthcare institutions for the treatment of a range of patients with empiric and confirmed cIAI. We are encouraged by the progress we have made during our first few months of launch, with more than 400 formulary reviews already completed or scheduled to occur by mid-year and a re-ordering rate for XERAVA above 70 percent. Further, as we look to the balance of 2019, we have made the decision to delay launching XERAVA in the EU5 independently and will instead continue to focus our resources on building momentum and supporting a successful launch in the U.S."

Mr. Macdonald continued, "With respect to our pipeline, we expect to complete our bronchopulmonary disposition study for TP-6076, targeted against Acinetobacter baumannii and other multidrug-resistant pathogens, later this year and look forward to presenting preclinical data on our new acute myeloid leukemia (AML) pipeline candidate, TP-2846, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta."

Key Milestones for 2019

Complete 400 formulary reviews for XERAVA by mid-year
Present preclinical data on TP-2846 at the AACR (Free AACR Whitepaper) Annual Meeting – 2Q 2019
Everest Medicines to begin Phase 3 clinical trial of eravacycline in cIAI in China – 2Q 2019
Complete bronchopulmonary disposition study for TP-6076 – 2H 2019
Fourth Quarter and Recent Highlights

Commercially Launched XERAVA for cIAI in the U.S.
The Company commercially launched XERAVA in the U.S. in mid-October 2018. XERAVA is now available for use in hospitals and healthcare institutions for the treatment of a range of patients with empiric and confirmed cIAI. The salesforce is focusing on institutions responsible for treating 90 percent of patients with Gram-negative infections. Currently, three antimicrobial susceptibility tests (ASTs) have been approved for commercial use including the Eravacycline Mast Disk by Hardy Diagnostics; the Eravacycline MIC Strip by Liofilchem, Inc.; and the Sensititre Plate by Thermo Fisher Scientific, Inc. Previously, more than 200 healthcare institutions ordered ASTs for research-use-only purposes.
Received Marketing Authorization from the European Commission (EC) for XERAVA in the European Union (EU)
In September, the EC adopted the July 2018 positive opinion issued by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) to grant marketing authorization for XERAVA for the treatment of cIAI in adults in all EU member states as well as Iceland, Liechtenstein and Norway.
Entered into Loan and Security Agreement with Solar Capital Limited
In November 2018, the Company entered into a loan agreement with Solar Capital Limited, providing up to $75 million, with $30 million funded at closing, which is being used to support the commercial launch of XERAVA and for general corporate purposes.
Announced New Preclinical Data on TP-2846 for AML to be Presented at the 2019 AACR (Free AACR Whitepaper) Annual Meeting
In February 2019, Tetraphase announced it will present three posters on TP-2846, the Company’s newly revealed pipeline candidate for AML, at the 2019 AACR (Free AACR Whitepaper) Annual Meeting taking place March 29 – April 3 at the Georgia World Congress Center in Atlanta. The poster presentations will include in vitro and in vivo data supporting TP-2846’s potential as a novel tetracycline antileukemia agent.
Approval of Everest Medicines’ Investigational New Drug (IND) Application for Eravacycline in cIAI by the China National Medical Products Administration (NMPA)
In June 2018, Everest Medicines, a C-Bridge Capital-backed biopharmaceutical company, which has the exclusive license to develop and commercialize eravacycline in China, Taiwan, Hong Kong, Macau, South Korea and Singapore, submitted an IND application to the China NMPA, formerly the China FDA. The IND was approved by China NMPA, and Everest expects to begin enrolling patients in its Phase 3 study of eravacycline in cIAI in the second quarter of 2019.
Presented XERAVA and TP-6076 Data at the Infectious Disease Society of America’s (IDSA) 2018 IDWeek
In October 2018, the Company presented data related to XERAVA and TP-6076 at IDSA’s IDWeek. Among the data presented were results from a post-hoc analysis of XERAVA Phase 3 data, which showed high clinical cure and microbiological eradication rates with XERAVA among patients with cIAI and concurrent bacteremia. Data from a Phase 1 randomized, placebo-controlled, double-blind, multiple-ascending-dose study demonstrating positive safety, tolerability and pharmacokinetic results for the Company’s novel, fully synthetic tetracycline, TP-6076, were also presented.
Presented XERAVA Data at the American College of Clinical Pharmacy (ACCP) 2018 Global Conference
At the ACCP 2018 Global Conference in October, the Company announced positive data from a post-hoc analysis of two Phase 3 trials of XERAVA in cIAI in higher-risk populations – obese patients and those with altered renal function. Similar clinical cure rates were observed for XERAVA in these populations across all classifications of renal function, further supporting that the drug is an effective empiric treatment for cIAI and may provide an alternative to antibiotics that require dosing modification in patients with altered renal function. XERAVA was also effective regardless of body mass index when dosed 1mg/kg IV every 12 hours, based on total body weight when compared to carbapenems.
Fourth Quarter and Full-Year 2018 Financial Results

As of December 31, 2018, Tetraphase had cash and cash equivalents of $107.8 million and 53.7 million shares outstanding. The Company expects that its cash and cash equivalents, as well as expected revenue, will be sufficient to fund operations into the third quarter of 2020.

For the fourth quarter of 2018, Tetraphase reported a net loss of $21.5 million, or $0.40 per share, compared to a net loss of $23.5 million, or $0.46 per share, for the same period in 2017. For the year ended December 31, 2018, Tetraphase reported a net loss of $72.2 million, or $1.37 per share, compared to a net loss of $114.8 million, or $2.63 per share, for the same period in 2017.

XERAVA product revenue for the fourth quarter and year ended December 31, 2018 was $178,000, reflecting sales of the product which was commercially introduced in the U.S. in mid-October 2018.

Total revenues were $4.3 million for the fourth quarter of 2018, compared to $2.5 million for the same period in 2017. Total revenues were $18.9 million for the year ended December 31, 2018, compared to $9.7 million for the same period in 2017. Total revenues for the fourth quarter and year ended December 31, 2018 consisted of XERAVA product revenue, license and collaboration revenue from the Company’s relationship with Everest Medicines and government contract revenue. The increases in total revenues for the fourth quarter and year ended December 31, 2018 compared to the same prior-year periods were primarily due to the collaboration and XERAVA revenue, neither of which existed in 2017.

Research and development (R&D) expenses for the fourth quarter of 2018 were $10.7 million, compared to $18.5 million for the same period in 2017. R&D expenses for the year ended December 31, 2018 were $54.9 million, compared to $101.7 million for the same period in 2017. The decreases in R&D expenses for the fourth quarter and year ended December 31, 2018 compared to the same prior-year periods were primarily due to lower clinical trial costs associated with the IGNITE Phase 3 clinical trials, which concluded in the first quarter of 2018, and a decrease in chemistry, manufacturing and controls (CMC) expenses for XERAVA.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2018 were $14.7 million, compared to $7.9 million for the same period in 2017. SG&A expenses for the year ended December 31, 2018 were $37.1 million, compared to $23.7 million for the same period in 2017. The increases in SG&A expenses for the fourth quarter and year ended December 31, 2018 compared to the same prior-year periods were primarily due to an increase in commercial launch-related expenses for XERAVA and related G&A infrastructure investments.

Conference Call and Webcast Information

Tetraphase will host a conference call today at 4:30 p.m. ET to discuss its financial results and provide an update on the Company. The call can be accessed by dialing 844-831-4023 (U.S. and Canada) or 731-256-5215 (international) and entering conference ID number 4187876. To access the live audio webcast, visit the "Investors — Events & Presentations" section of the Tetraphase website at www.tphase.com.

A replay of the conference call will be available from 7:30 p.m. ET on Thursday, March 14, 2019, through 7:30 p.m. ET on Thursday, March 21, 2019 and by dialing 855-859-2056 (U.S. and Canada) or 404-537-3406 (international). The conference ID number is 4187876. A replay of the webcast will be available on Tetraphase’s website for 90 days.

About XERAVATM

XERAVA (eravacycline for injection) is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections (cIAI) in patients 18 years of age and older. It is approved for use in the U.S. and Europe. XERAVA was investigated for the treatment of cIAI as part of the Company’s IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline) Phase 3 program. In the first pivotal Phase 3 trial in patients with cIAI, twice-daily intravenous (IV) eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to ertapenem and was well-tolerated. In the second Phase 3 clinical trial in patients with cIAI, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to meropenem and was well-tolerated. In both trials, XERAVA achieved high cure rates in patients with Gram-negative pathogens, including resistant isolates.

XERAVATM Important Safety Information

XERAVA is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections in patients 18 years of age and older.

XERAVA is not indicated for the treatment of complicated urinary tract infections.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs or to any of the excipients. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with XERAVA.

The use of XERAVA during tooth development (last half of pregnancy, infancy and childhood to the age of eight years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.

The use of XERAVA during the second and third trimester of pregnancy, infancy and childhood up to the age of eight years may cause reversible inhibition of bone growth.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis.

The most common adverse reactions observed in clinical trials (incidence ≥ 3%) were infusion site reactions, nausea, and vomiting.

XERAVA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased blood urea nitrogen, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial drugs, and may occur with XERAVA. Discontinue XERAVA if any of these adverse reactions are suspected.

To report SUSPECTED ADVERSE REACTIONS, contact Tetraphase Pharmaceuticals Inc., at 1-833-7-XERAVA (1-833-793-7282) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full prescribing information for XERAVA.

About Tetraphase Pharmaceuticals, Inc.

Tetraphase Pharmaceuticals, Inc., is a biopharmaceutical company using its proprietary chemistry technology to create novel tetracyclines for serious and life-threatening conditions, including bacterial infections caused by many of the multidrug-resistant bacteria highlighted as urgent public health threats by the World Health Organization and the Centers for Disease Control and Prevention. The Company has created more than 3,000 novel tetracycline compounds using its proprietary technology platform. Tetraphase’s lead product XERAVATM is approved for the treatment of complicated intra-abdominal infections by the U.S. Food and Drug Administration and the European Medicines Agency. The Company’s pipeline also includes TP-271 and TP-6076, which are in Phase 1 clinical trials, and TP-2846, which is in preclinical testing for acute myeloid leukemia. Please visit www.tphase.com for more company information.

On March 13, 2019 Protalix BioTherapeutics, Inc. (NYSE American:PLX, TASE:PLX), a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell-based expression system, ProCellEx, reported that it will postpone its 2018 financial results corporate update from Thursday, March 14, 2019, to Monday, March 18, 2019 at 8:30 am ET (Press release, Protalix, MAR 13, 2019, View Source;p=RssLanding&cat=news&id=2391209 [SID1234534282]).

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To participate in the conference call, please dial the following numbers prior to the start of the call: United States: (844) 358-6760; International: (478) 219-0004. Conference ID number 9583103.

The conference call will also be broadcast live and available for replay for two weeks on the Company’s website, www.protalix.com, in the Events Calendar of the Investors section. Please access the Company’s website at least 15 minutes ahead of the conference to register, download, and install any necessary audio software.