On March 12, 2020 Protalix BioTherapeutics, Inc. (NYSE American: PLX) (TASE: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the fourth quarter and full year ended December 31, 2019, and provided a business update on recent corporate and clinical developments (Press release, Protalix, MAR 12, 2020, View Source [SID1234555506]). The Company will discuss the clinical, corporate and financial highlights on a conference call and live webcast, scheduled for Thursday, March 12th, 2020 at 8:30 am EDT.

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"2019 was a pivotal year for Protalix, as we successfully expanded on our strong foundation and entered into a new phase of development as a world-class recombinant therapeutic company," said Dror Bashan, Protalix’s President and Chief Executive Officer. "With this continued forward momentum toward commercialization of our Fabry program, we believe Protalix is positioned for both near- and long-term success," he continued.

"We are increasingly enthusiastic about our PRX-102 asset now that we have three ongoing, fully-enrolled Phase III clinical trials of PRX-102, and as we anticipate our BLA submission to the U.S. Food and Drug Administration under the Accelerated Approval pathway next quarter," added Mr. Bashan. "Furthermore, we anticipate the final results of our BRIDGE and BRIGHT trials in the first and second halves of 2020, respectively, which will further support our portfolio of data regarding PRX-102. Protalix is firing on all cylinders right now, and the energy among the entire staff reached a new pinnacle in 2019."

"We anticipate 2020 to be a banner year for Protalix as we increase our focus on advancing our clinical pipeline, expanding sales in Brazil of Elelyso, our enzyme replacement therapy for the treatment of Gaucher disease, and leveraging commercial opportunities to expand our global footprint in the treatment of Fabry disease," he concluded.

Conference Call and Webcast Information

The Company will host a conference call on Thursday, March 12, 2020, at 8:30 am, Eastern Daylight Time, to review the clinical, corporate and financial highlights. To participate in the conference call, please dial the following numbers prior to the start of the call:

Domestic: 877-423-9813
International: 201-689-8573
Conference ID: 13699970
Webcast: View Source

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

2019 Full-Year and Recent Business Highlights

Clinical Advancements

·The Company and its collaboration partner, Chiesi Farmaceutici S.p.A., or Chiesi, plan the submission of a BLA for PRX-102 via the FDA’s Accelerated Approval pathway in the second quarter of 2020, based on data from the completed Phase I/II clinical trial of PRX-102 for the treatment of Fabry disease and the ongoing Phase III BRIDGE clinical trial.
Results from the Company’s Phase I/II clinical trial of PRX-102 were published in an article in the May 2019 edition of the Journal of Inherited Metabolic Disease.

·The Company announced positive 12-month interim on-treatment data from the BRIDGE study. The interim data demonstrate a mean improvement in kidney function in both male and female patients when switched from agalsidase alfa (Replagal) to PRX-102. The data will be included in the anticipated BLA filing to help to support the application.

·The Company and Chiesi announced the completion of enrollment in the Phase III BALANCE clinical trial. The head-to-head BALANCE study is designed to evaluate the safety and efficacy of PRX-102 compared to agalsidase beta (Fabrazyme) on renal function in Fabry patients with progressing kidney disease previously treated with agalsidase beta. To date, more than 66 patients are being treated in the Company’s various extension studies after opting to continue treatment with PRX-102 after completion of an initial study.

·Enrollment was completed in the Phase III BRIGHT clinical trial of PRX- 102, via intravenous infusions of 2 mg/kg administered every 4 weeks. Preliminary pharmacokinetic (PK) data showed PRX-102 to be well-tolerated; and infusion of 2 mg/kg PRX-102 administered every 4 weeks resulted in the presence of continuous active enzyme throughout the entire infusion interval. Infusions every 2 weeks is the current standard of care for the treatment of Fabry disease.

Corporate & Financial Developments

·The Company yesterday successfully secured securities purchase agreements to raise proceeds equal to $43.7 million through a private financing with a number of leading Israeli and U.S.- based investors, including Psagot Investment House, More Investment House, Highbridge Capital, UBS O’Connor, Rosalind Capital, and Alrov Properties and Lodging, among others. Rosario Capital and Houlihan Lokey served as financial advisors in the private placement.

·In December 2019, the Company held a special meeting of stockholders to propose the following two critical financial amendments, which stockholders ultimately approved:
oA reverse stock split (1-for-10); and
oA reduction in the total number of shares of the Company’s common stock that the Company is authorized to issue from 350 million to 120 million shares.

·In December 2019, the Company enhanced its Board of Directors with addition of two accomplished biopharmaceutical executives, Pol F. Boudes, M.D., and Gwen A. Melincoff.

·In August 2019, the Company’s Board of Directors unanimously elected Zeev Bronfeld, an independent director, as Chairman of the Board.

·In July 2019, the Company appointed Eyal Rubin as Senior Vice President and Chief Financial Officer.

·In May 2019, the Company appointed Dror Bashan as President and Chief Executive Officer.

Regulatory Advancements

·In February 2020, Protalix and Chiesi announced the receipt of an agreement letter from the FDA for the Initial Pediatric Study Plan (iPSP) for PRX-102 for the treatment of Fabry disease, outlining an agreed-upon approach to address the needs of pediatric Fabry patients.

Financial Results

For the year ended December 31, 2019, compared to the year ended December 31, 2018

·The Company recorded revenues from selling goods of $15.9 million for the year ended December 31, 2019, an increase of $6.9 million, or 77%, compared to revenues of $9.0 million for the same period of 2018. The increase is primarily due to higher sales of Elelyso in Brazil as well as an increase in sales of drug substance to Pfizer.

·Research and development expenses, net, were $44.6 million for the year ended December 31, 2019, an increase of $11.3 million, or 34%, compared to $33.3 million for the same period of 2018. The increase resulted primarily from an increase of $9.1 million in clinical trial related costs as well as a decrease of $2.1 million in grants received from the Israeli Innovation Authority.

·Selling, general and administrative expenses were $9.9 million for the year ended December 31, 2019, a decrease of $1.0 million, or 9%, compared to $10.9 million for the same period of 2018. The decrease resulted primarily from costs related to the Company’s U.S. Exclusive License and Supply Agreement that the Company entered into in 2018, which were not incurred in 2019.

·Net loss was $18.3 million for the year ended December 31, 2019, or $1.23 per share, basic and diluted, compared to a net loss of $26.5 million, or $1.80 per share, basic and diluted, for the same period of 2018.

·At December 31, 2019, the Company had $17.8 million in cash and cash equivalents.

For the three months ended December 31, 2019, compared to the three months ended December 31, 2018

·The Company recorded revenues from selling goods of $3.8 million during the three-month period ended December 31, 2019, an increase of $2.0 million, or 111%, compared to revenues of $1.8 million for the same period of 2018. The increase is primarily due to higher sales of drug substance to Pfizer Inc. as well as higher sales of Elelyso in Brazil.

·Research and development expenses, net, were $9.6 million for the three-month period ended each of December 31, 2019 and December 31, 2018.

·Selling, general and administrative expenses were $3.0 million for the three-month period ended December 31, 2019, an increase of $0.8 million, or 36%, compared to $2.2 million for the same period in 2018. The increase is primarily due to costs related to the efforts to evaluate and pursue strategic alternatives, business development advisory fees, and legal fees and costs related to replacement of the Chief Executive Officer.

·Net profit for the three months ended December 31, 2019 was $0.3 million, or $0.02 per share, basic and diluted, compared to a net loss of $5.4 million, or $0.40 per share, basic and diluted, for the three months ended December 31, 2018.

On March 12, 2020 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that the European Commission (EC) has approved VENCLYXTO (venetoclax) in combination with obinutuzumab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who were previously untreated (Press release, AbbVie, MAR 12, 2020, View Source [SID1234555505]). The approval is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein, Norway and the United Kingdom.

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"This approval underscores the growing utility of VENCLYXTO in treating CLL and demonstrates its clinical benefit as a chemotherapy-free combination therapy option for CLL patients in Europe who have not yet been treated," said Neil Gallagher, M.D., Ph.D., chief medical officer and vice president of development. "We look forward to bringing VENCLYXTO to even more patients who can potentially benefit from achieving a deep response and sustained progression free survival, with the added benefit of a finite treatment duration."

This is the third approval for VENCLYXTO, a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 is a protein that prevents cancer cells from undergoing apoptosis, the process that leads to the natural death or self-destruction of cancer cells. VENCLYXTO is also approved in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy, and as a monotherapy for the treatment of CLL in the presence or absence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor.

This most recent approval is based on results from the Phase 3 CLL14 clinical trial primary analysis (median follow up of 28 months), which demonstrated superior progression-free survival (PFS; the time on treatment without disease progression or death) as assessed by investigators in patients treated with VENCLYXTO plus obinutuzumab compared to patients who received a standard of care chemotherapy regimen of chlorambucil plus obinutuzumab (hazard ratio 0.35; 95% CI (0.23,0.53), p<0.0001, medians not yet reached). At an updated CLL14 efficacy analysis (median follow-up of 40 months), the median PFS had not been reached in the VENCLYXTO + obinutuzumab arm and was 35.6 months [95% CI: 33.7,40.7] in the obinutuzumab + chlorambucil arm (hazard ratio 0.31; 95% CI: 0.22, 0.44). The 36-month PFS estimate in the venetoclax plus obinutuzumab arm was 81.9% [95% CI: 76.5, 87.3] and in the obinutuzumab plus chlorambucil arm was 49.5% [95% CI: 42.4, 56.6]. Additionally, after completing one year of treatment, patients treated with the VENCLYXTO combination experienced deep response as measured by higher rates of undetectable minimal residual disease (MRD) or complete response (CR) as compared to patients receiving a standard of care regimen.1,5

In the trial, adverse events (AEs) were consistent with the known safety profiles of venetoclax and obinutuzumab alone. At least one AE of any grade occurred in 94.3% of patients in the venetoclax combination arm. The most common Grade 3/4 AEs were neutropenia and infections. Tumor lysis syndrome (TLS) was reported in three patients in the venetoclax plus obinutuzumab group (all during treatment with obinutuzumab and before venetoclax).1

"CLL is the most common of the nearly 95,000 new cases of leukemia in Europe each year, and chemotherapy is often the first line of treatment," said Michael Hallek, M.D., lead investigator of the CLL14 study, director of the Department of Internal Medicine and Center of Integrated Oncology at the University Hospital Cologne in Germany, and head of the German CLL Study Group. "Having the option to utilize a first-line, chemotherapy-free treatment combination that can produce a deep response, thus allowing patients to stop treatment, will change the way we treat CLL and have a significant impact on patients."

In January 2020, AbbVie announced that the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus obinutuzumab for the treatment of patients with previously untreated CLL.

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About Chronic Lymphocytic Leukemia
CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow. In 2018, approximately 95,000 new cases of leukemia were diagnosed in Europe.2 CLL is the most common form of leukemia in the Western Hemisphere, accounting for approximately one third of new leukemia diagnoses.3,4

About the CLL14 Trial
The randomized, multicenter, open-label, actively controlled Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of VENCLYXTO and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in patients with previously-untreated CLL and coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] score >6 or creatinine clearance <70 mL/min). The therapies were administered for a fixed duration of 12 cycles for VENCLYXTO in combination with six cycles of obinutuzumab. Cycles were comprised of 28 days. The trial enrolled 432 patients, all of whom were diagnosed according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and were previously untreated. The primary efficacy outcome was PFS as assessed by the investigator.1 Key secondary endpoints were MRD-negativity in peripheral blood and bone marrow, and overall and complete response rates.1

About VENCLYXTO (venetoclax tablets)
VENCLYXTO is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers.

VENCLYXTO is approved in more than 50 countries, including the U.S. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

VENCLYXTO (venetoclax) EU Indication and Summary of Important Safety Information5

Indication
Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B?cell receptor pathway inhibitor, or
in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B?cell receptor pathway inhibitor.
Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use
Tumour lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS. Blood chemistries should be monitored, and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. Serious infections including events of sepsis with fatal outcome have been reported. Patients require monitoring of signs and symptoms of infection and prompt treatment. Supportive measures including antimicrobials for any signs of infection should be considered.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.

Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (≥20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently reported serious adverse reactions (≥2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (≥2%) were pneumonia and febrile neutropenia.

Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and MURANO studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in the CLL14 study, in 15% of patients treated with the combination of venetoclax and rituximab in the MURANO study and 14% of patients treated with venetoclax in the monotherapy studies.

Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.

On March 12, 2020 Thermo Fisher Scientific reported it has signed an agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to co-develop a companion diagnostic (CDx) in oncology (Press release, Thermo Fisher Scientific, MAR 12, 2020, View Source [SID1234555504]). The CDx will support clinical trial enrollment globally.

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Under the agreement, Thermo Fisher Scientific will collaborate with Janssen Research & Development, LLC scientists to validate multiple biomarkers for use with Thermo Fisher’s Oncomine Dx Target Test, which will be used to identify variant-positive patients for enrollment into clinical trials focused on non-small cell lung cancer (NSCLC). Additional indications in oncology may follow as part of the agreement.

Oncomine Dx Target Test is a next-generation sequencing (NGS) assay that contains 46 cancer-related biomarkers and a workflow that features a fast turnaround time and the lowest sample requirements on the market for detection of both DNA and RNA variants.

NGS is an established method of identifying gene variants at the center of several clinical trials or which are targeted by on-market and emerging therapies for cancer. Since its approval by the U.S. Food and Drug Administration in 2017, Oncomine Dx Target Test has been the focus of multiple drug development and clinical trial support agreements between Thermo Fisher and international pharmaceutical companies.

"The ability of the Oncomine Dx Target Test to rapidly detect variants of interest from very small quantities of DNA or RNA samples makes this technology ideally suited to support development programs requiring an NGS-based workflow that delivers actionable insights consistently," said Peter Silvester, senior vice president and president of Life Sciences Solutions at Thermo Fisher Scientific. "We are confident that this approach to patient stratification helps expedite drug development initiatives which ultimately are designed to promote better health outcomes through targeted therapies."

On March 12, 2020 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to developing and commercializing next-generation medicines to improve the lives of patients with immune-mediated diseases, reported financial results for the year ended December 31, 2019 and provided an update on anticipated clinical milestones (Press release, Aldeyra Therapeutics, MAR 12, 2020, View Source [SID1234555503]).

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"2019 was a year of continued momentum for our lead programs, as we reported statistically significant and clinical relevant data that underscored the potential of reproxalap as a first-line therapy in allergic conjunctivitis and dry eye disease, conditions that in the aggregate affect more than one billion people worldwide," stated Todd C. Brady, M.D., President and CEO of Aldeyra. "Reproxalap potentially represents a highly differentiated mechanism of action compared with existing therapies. We are excited about the market opportunities for reproxalap as we continue to advance towards the completion of clinical development."

Recent Highlights and Upcoming Milestones

Allergic Conjunctivitis: Aldeyra expects to complete the INVIGORATE Phase 3 clinical trial of topical ocular reproxalap in the second half of 2020. In 2019, Aldeyra announced achievement of the primary endpoint of the Phase 3 ALLEVIATE Trial in allergic conjunctivitis, as well as statistically significant reductions in ocular itching and redness in an allergen chamber clinical trial.

Dry Eye Disease: Based on the achievement of symptom endpoints in two well-controlled clinical trials, Aldeyra plans to meet with the U.S. Food and Drug Administration (FDA) prior to initiating Part 2 of the RENEW Trial, and plans to provide an update on future development in dry eye disease following FDA feedback, expected in the second half of 2020.

Proliferative Vitreoretinopathy (PVR): Aldeyra is currently enrolling patients in the GUARD Phase 3 Trial of ADX-2191, a novel anti-inflammatory and anti-proliferative agent for the prevention of PVR, a rare sight-threatening condition with no approved treatment. The GUARD Trial is a two-part, multi-center, randomized, controlled, adaptive clinical trial evaluating the efficacy of intravitreal injections of ADX-2191 versus standard-of-care for the prevention of PVR. The trial will compare recurrent retinal detachment rates over a 24-week period following surgical repair of retinal detachment due to PVR or open globe injury. Enrollment is currently expected to be completed in 2021.

Systemic Autoimmune Disease: A single and multiple ascending dose Phase 1 clinical trial has been completed for ADX-629, a novel orally administered RASP inhibitor in development for the treatment of systemic autoimmune disease and potentially other serious medical conditions. Top-line results are expected in the second quarter of this year. Initiation of Phase 2 clinical testing is planned for the second half of 2020.

Strategic Prioritization of Late-Stage Programs in Ocular Disease

In a separate news release issued earlier today, Aldeyra announced strategic prioritization of late-stage ocular disease programs in allergic conjunctivitis, dry eye disease, and proliferative vitreoretinopathy. In conjunction with the strategic prioritization, Aldeyra appointed ophthalmology drug development expert James A. Gow, M.D., as Senior Vice President of Clinical Development.

Aldeyra has elected to place on hold its clinical development of topical dermal reproxalap for the treatment of ichthyosis associated with Sjogren-Larsson Syndrome and ADX-1612 for the treatment of post-transplant lymphoproliferative disorder. The initiatives to prioritize the portfolio are expected to extend the company’s cash runway through the end of 2021.

Year Ended December 31, 2019 Financial Review

Aldeyra reported a net loss of $60.8 million for the year ended December 31, 2019, compared with a net loss of $38.9 million in 2018. Basic net loss per share was $2.24 for the year ended December 31, 2019, compared with $1.79 per share in 2018. Losses have resulted from the costs of Aldeyra’s clinical trials and research and development programs, as well as from general and administrative expenses.

Research and development expenses were approximately $44.4 million for the year ended December 31, 2019, compared with approximately $29.8 million for the year ended December 31, 2018. The increase of $14.6 million is primarily related to the increase in clinical and preclinical development and manufacturing costs; an increase in personnel costs; and non-cash compensation costs related to a portion of upfront acquisition consideration that is subject to vesting based on continued service.

Acquired in-process research and development expenses were $6.6 million for the year ended December 31, 2019. Aldeyra did not have acquired in-process research and development expenses for the year ended December 31, 2018. The $6.6 million increase is related to the in-process research and development expenses associated with the January 2019 acquisition of Helio Vision.

General and administrative expenses were approximately $12.2 million for the year ended December 31, 2019, compared with $9.9 million for the year ended December 31, 2018. The increase of $2.3 million is primarily related to an increase in personnel costs and public company costs related to compliance with the Sarbanes-Oxley Act of 2002.

Total operating expenses were approximately $63.1 million for the year ended December 31, 2019, compared with total operating expenses of approximately $39.7 million for the year ended December 31, 2018.

Cash, cash equivalents, and marketable securities were $73.4 million as of December 31, 2019.

Conference Call & Webcast Information

Aldeyra will host a conference call today at 8:00 a.m. ET to discuss its full-year 2019 financial results and provide a corporate update. The dial-in numbers are (866) 211-4098 for domestic callers and (647) 689-6613 for international callers. The Conference ID number is 9984588.

A live webcast of the conference call will also be available on the Investors Relations section of the Aldeyra Therapeutics website at View Source After the live webcast, the event will remain archived on the Aldeyra Therapeutics website for 90 days.

About Reproxalap

Reproxalap is a novel, small-molecule immune-modulating covalent inhibitor of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease, and lead to activation of intracellular inflammatory factors, including NF-kB, inflammasomes, and Scavenger Receptor A. Reproxalap’s mechanism of action has been validated with the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications. Topical ocular reproxalap has now been studied in more than 1,100 patients with no observed safety concerns reported; mild instillation site irritation is the most commonly reported adverse event in clinical trials.

About ADX-2191

ADX-2191, an intravitreal formulation of methotrexate, has received orphan drug and fast track designations from the FDA for the prevention of PVR. The observed clinical activity of ADX-2191 in patients with PVR is believed to be the result of down-regulation of aberrant retinal cell proliferation and activity, thereby leading to reduced retinal scarring that is characteristic of PVR. Aldeyra retains an exclusive license to certain patents related to the use of ADX-2191 for the prevention of PVR.

On March 12, 2020 Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical company focused on commercializing its novel tetracycline XERAVA to treat serious and life-threatening infections, reported financial results for the fourth quarter and year ended December 31, 2019, provided an overview of recent achievements, and highlighted key milestones for 2020 (Press release, Tetraphase, MAR 12, 2020, View Source [SID1234555502]).

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"We made significant progress throughout 2019, ending the year with $3.6 million in XERAVA net sales for the full year and a quarter-to-quarter net revenue increase in the fourth quarter of 2019 of 49.3%. Our sales consist solely of actual use and not stocking retail or other channels," said Larry Edwards, President and Chief Executive Officer of Tetraphase. "We believe XERAVA is a critically important new addition to the hospital antibiotic armamentarium, and we remain committed to increasing formulary uptake and reaching all of our targeted accounts. The reorganization efforts we undertook in 2019 to create a streamlined organization singularly focused on the commercialization of XERAVA, including the elimination of our research and development function, are central to the success of our mission. With two recently completed equity offerings in November 2019 and January 2020 adding to our balance sheet, we are now in a stronger financial position to execute on our goals."

Key Milestones for 2020

Complete 143 formulary reviews for XERAVA by mid-year
Continue pulling through appropriate utilization at the 1,200 hospitals at which XERAVA is on formulary or available
Continue double-digit quarter over quarter growth for XERAVA
Create additional opportunities in TIER 2 and TIER 3 Accounts
Out-license pipeline assets and enter into arrangements for commercialization of XERAVA in Europe and Latin America
Filing by Everest Medicines for regulatory approval of XERAVA for complicated intra-abdominal infections in China in the fourth quarter of 2020
Fourth Quarter and Recent Highlights

Continued to Progress Launch of XERAVA in U.S. Hospitals With High Antibiotic Usage

The Company continues to see increased formulary uptake, with a 99% success rate for all formulary reviews to date and $3.6 million in XERAVA sales for the full-year 2019. XERAVA sales for 2018 were $178,000. Tetraphase’s salesforce is now focusing on bringing XERAVA to both Tier 1 as well as Tier 2 institutions, which are the highest users of antibiotics defined by days of therapy. The reorder rate for XERAVA continues to be strong, with reorder rates as high as 67% for all accounts and approximately 77% within the Tier 1 account segment. XERAVA is on formulary or available at more than 1,200 accounts and approximately 143 formulary reviews are pending or planned to take place over the next six months.
Completed Two Equity Financings Totaling Net Proceeds of $23.0 Million

In January 2020, the Company completed a private placement with Armistice Capital, LLC, a healthcare-focused institutional investor, priced at-the-market, that generated gross proceeds of approximately $10 million. In addition, the Company concurrently completed a registered direct offering with certain healthcare-focused institutional investors, priced at-the-market, that generated gross proceeds of approximately $7.5 million. The net proceeds from the concurrent January 2020 private placement and registered direct offering were approximately $15.9 million.

In November 2019, the Company completed a registered direct offering with Armistice Capital, LLC, a healthcare-focused institutional investor, priced at-the-market, that generated net proceeds of approximately $7.1 million.

The Company issued warrants in connection with all of the financings listed above.
Fourth Quarter and Full-Year 2019 Financial Results

As of December 31, 2019, Tetraphase had cash and cash equivalents of $21.2 million and 3.5 million shares outstanding. Subsequent to the end of the fourth quarter, the Company raised an additional $15.9 million in net proceeds via an equity offering. The Company expects that its cash and cash equivalents, including the equity proceeds and its expected revenue, will be sufficient to fund operations into the first quarter of 2021.

For the fourth quarter of 2019, Tetraphase reported a net loss of $11.4 million, or $2.75 per share, compared to a net loss of $21.5 million, or $8.00 per share, for the same period in 2018, driven by both increased product revenues and lower operating expenses. For the year ended December 31, 2019, Tetraphase reported a net loss of $70.1 million, or $22.85 per share, compared to a net loss of $72.2 million, or $27.48 per share, for the same period in 2018.

Total revenues were $1.7 million for the fourth quarter of 2019, of which $1.5 million was from sales of XERAVA, compared to $4.3 million for the same period in 2018, of which $178,000 was from sales of XERAVA. Total revenues were $7.4 million for the year ended December 31, 2019, of which $3.6 million was from sales of XERAVA, compared to $18.9 million for the same period in 2018, of which $178,000 was from sales of XERAVA. Total revenues for the fourth quarter and year ended December 31, 2019 consisted of XERAVA product revenue, license and collaboration revenue from the Company’s relationship with Everest Medicines and government contract revenue. The primary driver of the year over year decrease in revenue was a reduction in the up front and regulatory milestones received from the Company’s relationship with Everest Medicines and the wind down of its government awards and grants and the related revenue.

Research and development (R&D) expenses for the fourth quarter of 2019 were $2.5 million, compared to $10.7 million for the same period in 2018. R&D expenses for the year ended December 31, 2019 were $22.8 million, compared to $54.9 million for the same period in 2018. The significant year over year decrease in R&D expenses was driven by the completion of XERAVA development and our corporate reorganization in June 2019, which included the cessation of development of our pipeline candidates.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2019 were $9.3 million, compared to $14.7 million for the same period in 2018. SG&A expenses for the year ended December 31, 2019 were $49.0 million, compared to $37.1 million for the same period in 2018. The decrease in fourth quarter 2019 SG&A expenses compared to fourth quarter 2018 SG&A expenses was driven by our 2019 corporate reorganization and by up-front Xerava launch expenses incurred in the fourth quarter of 2018. The increase in full year 2019 SG&A expenses compared to full year 2018 SG&A expenses was driven primarily by a full year of commercial and medical affairs expenses in 2019 following the fourth quarter 2018 launch of Xerava.

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. 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) XERAVA 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 XERAVA 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.