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 14, 2019 Novelion Therapeutics Inc. (NASDAQ: NVLN), a biopharmaceutical company dedicated to developing and commercializing therapies for individuals living with rare diseases ("Novelion" or the "Company"), today reported financial results for the fourth quarter and year ended December 31, 2018 (Press release, QLT, MAR 14, 2019, View Source [SID1234534329]).

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Novelion’s Interim Chief Executive Officer Ben Harshbarger commented, "We are pleased with our fourth quarter results which reflect strong revenue performance and show meaningful impact from the cost reduction initiatives executed throughout 2018. We remain focused on undertaking a comprehensive capital restructuring and also on delivering our two very important rare disease therapies to indicated patients in need."

Business Update

Following marketing authorization of MYALEPTA (metreleptin) for generalized lipodystrophy (GL) and partial lipodystrophy (PL) by the EMA in July, our subsidiary Aegerion Pharmaceuticals commenced the pricing and reimbursement processes in key EU markets. Reimbursement decisions in many of the key EU markets are anticipated throughout 2019. MYALEPTA sales growth in 2018 was supported by named patient sales programs, which allow for sales on an unsolicited basis prior to regulatory approval and/or pricing and reimbursement decisions, as well as the launch of MYALEPTA in Germany in the fourth quarter.

In February 2019, Aegerion entered into an exclusive licensing agreement with Recordati Rare Diseases Inc. ("Recordati") for the commercialization of JUXTAPID (lomitapide) in Japan. The agreement includes exclusive rights in Japan for Recordati to commercialize JUXTAPID for the current approved indication, homozygous familial hypercholesterolemia (HoFH). The terms of, and use of proceeds from, the Recordati licensing agreement are described more fully in Novelion’s Form 8-K filed on February 6, 2019.

In January 2019, Aegerion held a meeting with the U.S. Food and Drug Administration (FDA) to obtain feedback on the design of the placebo-controlled study that will be required in order to pursue the PL indication for MYALEPT in the U.S. The Company is assessing feedback on the study design and integrating it into the Phase 3 study protocol.

Aegerion plans to file for regulatory approvals for metreleptin in GL and PL in certain key markets outside the U.S. and EU, including Brazil, in 2019.

As previously announced, Novelion and Aegerion have each engaged advisors to independently explore and advise them on all available strategic alternatives regarding the Company’s capital structure, such as a restructuring of Aegerion’s Convertible Notes due August 2019 (including a restructuring that would likely involve a debt for equity swap), a sale or merger of Novelion or Aegerion, or the sale or other disposition of certain businesses or assets. The implementation of one or more of such transactions (or the failure to complete any such transaction or transactions) will likely require Aegerion, and could require Novelion, to seek the protections of applicable bankruptcy laws allowing for corporations to seek to restructure their debts and other affairs under a reorganization.
Fourth Quarter 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $15.2 million in the fourth quarter of 2018, compared to $20.1 million for the same period in 2017, $8.2 million, or 53.9%, of which was from prescriptions written in the U.S. and $0.8 million of which was royalty revenue from sales of JUXTAPID in the EMEA region. The JUXTAPID revenue decline in the fourth quarter of 2018 compared to the same period in 2017 was primarily due to product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy.

MYALEPT: Novelion reported net revenues of MYALEPT of $25.5 million in the fourth quarter of 2018, compared to $18.8 million for the same period in 2017, $13.4 million, or 52.5%, of which was from prescriptions written in the U.S. MYALEPT revenue growth in the fourth quarter was driven by increased sales in all key markets.

GAAP total net revenues for the fourth quarter of 2018 were $40.7 million compared to $38.9 million for the same period in 2017.

Cost of product sales for the fourth quarter of 2018 was $18.0 million compared to $17.0 million for the same period in 2017, resulting in stable year-over-year fourth quarter gross margins.

GAAP total operating expenses for the fourth quarter of 2018 were $21.7 million compared to total operating expenses of $35.9 million, a 39.6% reduction compared to the same period in 2017. GAAP SG&A expenses were $14.1 million in the fourth quarter of 2018 compared to $24.1 million for the same period in 2017. GAAP R&D expenses were $7.7 million in the fourth quarter of 2018 compared to $11.8 million for the same period in 2017.

On a non-GAAP basis, during the fourth quarter of 2018, SG&A expenses were $13.0 million compared to $22.5 million for the same period in 2017. The 42.2% decrease in non-GAAP SG&A expenses in the fourth quarter of 2018 compared with the same period in 2017 was primarily related to cost reduction initiatives executed throughout 2018.

On a non-GAAP basis, during the fourth quarter of 2018, R&D expenses decreased 33.6% to $7.7 million compared to $11.6 million for the same period in 2017, reflecting cost reduction initiatives executed throughout 2018.

GAAP net loss in the fourth quarter of 2018 was $19.4 million, an improvement of approximately 21.1% compared to GAAP net loss of $24.6 million during the same period in 2017.

On a non-GAAP basis, net income was $2.9 million in the fourth quarter of 2018 compared to a net loss of $3.3 million for the same period in 2017.

A full reconciliation of the GAAP financial results to non-GAAP financial results is included in the financial information tables below.

Full Year 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $59.1 million for the year ended December 31, 2018, compared to $72.1 million for 2017. The decline in sales resulted from product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy. Named patient sales of JUXTAPID in Brazil totaled $0.4 million in 2018, compared to $6.7 million of JUXTAPID named patient sales in Brazil in 2017. Revenue growth in Japan in 2018 helped offset the sales decline in the U.S. and Brazil.

MYALEPT: Novelion reported net revenues of MYALEPT of $71.4 million for the year ended December 31, 2018, compared to $66.3 million for 2017. The increase was primarily attributable to revenues in France, Germany and Turkey. In addition, 2017 MYALEPT sales benefited from $2.3 million of one-time deferred revenue recognition in the U.S.

GAAP total net revenues for the year ended December 31, 2018 were $130.4 million compared to $138.4 million for 2017.

Cost of product sales for the year ended December 31, 2018 was $59.7 million compared to $77.2 million for 2017, resulting in improved gross margin. The improvement in 2018 was primarily a result of higher reserves in 2017 for excess and obsolete inventory which were charged to cost of product sales, partially offset by a higher royalty rate on U.S. sales of metreleptin in 2018.

GAAP total operating expenses for the year ended December 31, 2018 were $120.8 million compared to total operating expenses of $148.0 million for 2017. GAAP SG&A expenses were $79.8 million for the year ended December 31, 2018 compared to $96.5 million for 2017. GAAP R&D expenses were $38.8 million for the year ended December 31, 2018 compared to $49.0 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, SG&A expenses decreased 20.0% to $72.6 million compared to $90.7 million for 2017, primarily as a result of cost reduction initiatives executed throughout 2018. Restructuring charges for 2018 were $2.2 million, compared with restructuring charges of $2.5 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, R&D expenses decreased 20.5% to $38.3 million compared to $48.2 million for 2017 due primarily to cost reduction initiatives executed throughout 2018.

GAAP net loss for the year ended December 31, 2018 was $108.3 million compared to GAAP net loss of $126.7 million for 2017.

Net loss on a non-GAAP basis for the year ended December 31, 2018 was $25.3 million, compared to $30.0 million for 2017.

As of December 31, 2018, the Company’s consolidated unrestricted cash balance was $45.2 million, compared to $55.4 million at December 31, 2017. Novelion’s consolidated cash as of December 31, 2018 includes $13.3 million at Novelion and $31.9 million at the Aegerion subsidiary level.

Debt and Government Settlement Payments

As of December 31, 2018, Aegerion’s debt liabilities and government settlement payments included $302.5 million in outstanding principal under Aegerion’s Convertible Notes due August 15, 2019, $75.9 million in outstanding principal (including paid in kind fees and interest) under Aegerion’s secured term loans having a maturity date of June 30, 2019, $37.1 million outstanding under Aegerion’s secured intercompany term loan with Novelion, as lender, which has a maturity date of July 1, 2019 (which term loan amounts were subsequently reduced by repayments received from the Recordati license transaction described above), as well as $31.1 million owed under Aegerion’s settlements with the Department of Justice and the U.S. Securities and Exchange Commission (the "Commission"), payable in prescribed installments until the first quarter of 2021.

Financial Guidance

Novelion expects total net revenues in 2019 to be between $160.0 and $175.0 million, including $30.0 million of licensing revenues, in the form of the $25.0 million upfront licensing payment and $5.0 payment upon transfer of the marketing authorization to Recordati, resulting from the Recordati transaction.

On March 14, 2019 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that it has entered into a master clinical supply agreement under which Roche will supply atezolizumab (Tecentriq) to Infinity for use in MARIO-3, a Phase 2 multi-arm combination cohort study (Press release, Infinity Pharmaceuticals, MAR 14, 2019, View Source [SID1234534363]). The study will evaluate IPI-549, Infinity’s first-in-class, oral immuno-oncology product candidate targeting immune-suppressive tumor-associated myeloid cells through selective inhibition of phosphoinositide-3-kinase (PI3K)-gamma, in combinations with Tecentriq and Abraxane (nab-paclitaxel) in front-line triple negative breast cancer (TNBC) and in combination with Tecentriq and Avastin (bevacizumab) in front-line renal cell cancer (RCC) beginning in the second half of 2019.

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"We are very pleased to have entered into this agreement with Roche to evaluate combinations including IPI-549 and Tecentriq in front-line solid tumor settings," said Sam Agresta, M.D., M.P.H., Chief Medical Officer at Infinity. "MARIO-3 is a key part of our strategy to expand the breadth and depth of the development of IPI-549 into earlier lines of therapy and in combination with potentially transformative new treatment regimens for patients. We look forward to initiating MARIO-3 later this year."

About Infinity Pharmaceuticals and IPI-549

Infinity is an innovative biopharmaceutical company dedicated to advancing novel medicines for people with cancer. Infinity is advancing IPI-549, a first-in-class, oral immuno-oncology development candidate that selectively inhibits PI3K-gamma, in multiple clinical studies. MARIO-1 is an ongoing Phase 1/1b study evaluating IPI-549 as a monotherapy and in combination with Opdivo (nivolumab) in approximately 225 patients with advanced solid tumors including patients refractory to anti-PD-1 therapy. Infinity intends to initiate MARIO-275, a global, randomized, combination study of IPI-549 combined with Opdivo in I/O naïve urothelial cancer patients, as well as to initiate MARIO-3, the first IPI-549 combination study in front-line advanced cancer patients. MARIO-3 will evaluate IPI-549 in combination with Tecentriq and Abraxane in front-line TNBC and in combination with Tecentriq and Avastin in front-line RCC. With the addition of MARIO-275 and MARIO-3 to the ongoing MARIO-1 study, Infinity will be evaluating IPI-549 in the anti-PD-1 refractory, I/O-naïve, and front-line settings. For more information on Infinity, please refer to Infinity’s website at www.infi.com.

On March 14, 2019 Kitov Pharma (NASDAQ/TASE: KTOV), an innovative pharmaceutical company, reported it has signed an agreement to acquire FameWave Ltd., a privately held biopharmaceutical company developing CM-24, a clinical stage monoclonal antibody targeting CEACAM1, a novel immune checkpoint (Press release, Kitov Pharmaceuticals , MAR 14, 2019, View Source [SID1234534309]). Kitov is planning initiation of a Phase I/II study in early 2020 to evaluate the safety and efficacy of CM-24 in combination with an anti PD-1 inhibitor. Kitov to host a conference call to discuss the transaction. The scheduling of the call will be announced separately.

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"Combining this transaction with our proprietary NT219 program, Kitov will become a clinical stage oncology company backed by the support of leading global life science funds. With the NT219 and CM-24 oncology candidates, we are opening an exciting future for Kitov and I’m looking forward to building on this momentum. We are very pleased that the investment and support of three leading global life science funds will enable Kitov to advance our clinical programs and expand our institutional investor base," stated Kitov CEO, Isaac Israel.

"The acquisition of CM-24 is a tremendous opportunity for Kitov and our shareholders. We believe CM-24 has the potential to treat recurrent and advanced stage cancers including ovarian, colorectal, melanoma, lung, bladder and gastric cancers, and that our Phase I/II trial design could result in a strong display of the drug’s efficacy to the benefit of patients and their families. The journey Kitov started with Consensi’s FDA approval and our recently announced distribution partnership for Consensi in the US, when combined with our plans to submit an IND for NT-219 in 2019 and the acquisition of CM-24, transforms Kitov into a robust immune-oncology development company," Mr. Israel concluded.

Preclinical studies provide strong justification for CM-24’s mechanism of action in activating the immune system through multiple pathways as validated by world renowned researchers at Harvard Medical School and MIT, in an article published in Nature* as well as by Prof. Gal Markel from the Tel Hashomer Medical Center**. Additional preclinical studies showed that a combination of CM-24 with a PD-1 antibody resulted in a synergistic anti-cancer effect. Kitov plans to explore higher doses and to test CM-24 in combination with an anti PD-1 inhibitor. A significant amount of data is available for the existing Investigational New Drug (IND) to support the continuation of the clinical studies.

FameWave will enter into a joint clinical collaboration agreement, which is now in an advanced stage of negotiation with a major pharmaceutical company, for a planned Phase I/II study of CM-24 in combination with a PD-1 antibody in early 2020, with preliminary data expected in late 2020.

On March 14, 2019 AVEO Oncology (NASDAQ: AVEO) reported financial results for the full year ended December 31, 2018 and provided a business update (Press release, AVEO, MAR 14, 2019, View Source [SID1234534330]).

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"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer"

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"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer," said Michael Bailey, president and chief executive officer of AVEO. "We continue to believe that there is a significant potential commercial opportunity for an active and well tolerated therapy within the third plus line of therapy, particularly one that demonstrated activity in a highly refractory patient population that has received prior PD-1 treatment. We are hopeful that the positive PFS outcomes from TIVO-3 translate into an improved overall survival hazard ratio and look forward to reporting a more mature interim OS outcome in the fourth quarter of 2019."

Recent Highlights

Presented Topline Results from TIVO-3 During an Oral Presentation at the 2019 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium. In February 2019, AVEO presented topline results from the TIVO-3 trial, AVEO’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in 350 subjects with refractory advanced or metastatic renal cell carcinoma (RCC) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium held February 14-16, 2019 in San Francisco. The results were presented during an oral presentation titled "TIVO-3: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC)." A copy of the presentation is currently available in the Publications & Presentation section of AVEO’s website.

The presentation noted that the TIVO-3 trial met its primary endpoint of demonstrating a statistically significant benefit in median progression-free survival (PFS). Median PFS for tivozanib was also longer than sorafenib both in patients who received prior PD-1 therapy and those who received two prior VEGF TKI therapies. The secondary endpoint of overall response rate also demonstrated a statistically significant improvement for patients receiving tivozanib compared to sorafenib.

The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis. As presented, the preliminary OS analysis conducted at an October 4, 2018 data cutoff date, which included additional patients previously lost to follow-up, showed a non-statistically significant difference in OS favoring sorafenib (hazard ratio: 1.12, p-value: 0.44).

Tivozanib was generally well-tolerated relative to sorafenib, with reported grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. The improved tolerability of tivozanib was evident in the lower rates of dose reductions and interruptions for toxicity in patients receiving tivozanib compared to those receiving sorafenib. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.
Announced NDA Timing Update. In January 2019, the U.S. Food and Drug Administration (FDA) recommended that AVEO not submit a New Drug Application (NDA) for tivozanib at this time using the preliminary OS results from the TIVO-3 trial. The FDA indicated that these preliminary OS results do not allay their concerns about the potential detriment in OS outlined in the Complete Response Letter dated June 6, 2013. AVEO now plans to make an NDA filing decision following the availability of more mature OS results. AVEO intends to conduct an additional interim OS analysis in August 2019, the results of which are expected to be reported in the fourth quarter of 2019.
Data from Phase 1b Expansion Cohort of Ficlatuzumab and Cytarabine in Relapsed and Refractory AML to be Presented at 2019 AACR (Free AACR Whitepaper) Annual Meeting. Data from the investigator-sponsored Phase 1b expansion cohort evaluating the safety and tolerability of ficlatuzumab, AVEO’s potent hepatocyte growth factor (HGF) inhibitory antibody, in combination with cytarabine in patients with relapsed and refractory acute myeloid leukemia (AML) will be presented during a poster session at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The presentation, titled, "Cyfi: Results from a Phase 1b expansion cohort of anti-hepatocyte growth factor and cytarabine in relapsed and refractory AML" (abstract CT078 / 2) will be featured during a poster session (Session PO.CT03) on Monday, April 1, 2019 from 1:00-5:00pm Eastern Time.
Entered Immuno-Oncology Clinical Supply Agreement with AstraZeneca. In December 2018, AVEO entered into a clinical supply agreement with AstraZeneca to evaluate the safety and efficacy of AstraZeneca’s IMFINZI (durvalumab), a human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in combination with tivozanib in first-line hepatocellular carcinoma, or liver cancer, in a Phase 1/2 study. AVEO will serve as the study sponsor; each party will contribute the clinical supply of its study drug and study costs will be otherwise shared equally. The Phase 1 portion of the study is expected to commence this year.
Earned $2 Million Milestone Payment from EUSA Pharma. In November 2018, AVEO announced the triggering of a $2 million milestone payment from EUSA Pharma related to the reimbursement in Germany for FOTIVDA as a first line treatment of adult patients with advanced RCC.
Extended Debt Facility Interest-Only Period. In December 2018, AVEO announced a six-month extension to the interest-only period under its existing amended and restated loan and security agreement with Hercules Capital, Inc. The extension was granted as a result of achieving certain predefined requirements under the agreement, including successfully meeting the primary endpoint of the TIVO-3 trial.
Raised $7.5 Million Under the Sales Agreement with SVB Leerink, Extending Financial Runway. In February 2019, AVEO raised $7.5 million through its sales agreement with SVB Leerink. Approximately $32 million of shares remain available for future issuance and sale pursuant to the sales agreement, which was originally entered into in February 2018. AVEO believes that the proceeds generated in February 2019 through the sales agreement, together with its available cash, cash equivalents, and marketable securities at December 31, 2018, and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, will allow it to fund planned operations into the first quarter of 2020.
Full Year 2018 Financial Highlights

AVEO ended 2018 with $24.4 million in cash, cash equivalents and marketable securities as compared with $33.5 million at December 31, 2017.
Total revenue for 2018 was approximately $5.4 million compared with $7.6 million for 2017.
Research and development expense for 2018 was $20.7 million compared with $25.2 million for 2017.
General and administrative expense for 2018 was $10.8 million compared with $9.1 million for 2017.
Net loss for 2018 was $5.3 million, or a loss of $0.04 and $0.19 per basic and diluted share, respectively, compared with a net loss of $65.0 million for 2017, or a loss of $0.61 per basic and diluted share.
The 2018 net loss was partially offset by an approximate $19.9 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from the decrease in the stock price that occurred within the fiscal year. In 2017, the non-cash loss attributable to the increase in the fair value of such warrant liability was $33.7 million.
Financial Guidance

AVEO believes that its $24.4 million in cash, cash equivalents, and marketable securities at the end of 2018, together with the additional $7.5 million raised from sales under its sales agreement with SVB Leerink in February 2019 and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, would allow it to fund planned operations into the first quarter of 2020. This estimate assumes no receipt of additional milestones from AVEO’s partners, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of outstanding warrants issued in connection with the 2016 private placement or outstanding warrants issued in connection with the recent settlement of the securities class action litigation.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal and breast cancers. In addition, a new formulation of tivozanib is in pre-clinical development for the treatment of age-related macular degeneration.