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Synlogic Presents Preclinical Data from First Synthetic BioticTM Clinical Candidate in Immuno-Oncology at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting

On November 6, 2018 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage drug discovery and development company applying synthetic biology to beneficial microbes to develop novel living medicines, reported the presentation of preclinical data from its first immuno-oncology (IO) program at the 33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2018) (Press release, Synlogic, NOV 6, 2018, View Source [SID1234530844]). Synlogic’s first Synthetic Biotic clinical candidate (SYNB1891) is designed to induce the production of type I interferon (IFN) through dual activation of innate immune pathways. Data that will be presented at SITC (Free SITC Whitepaper) 2018 demonstrate that SYNB1891 generated significant anti-tumor activity, systemic immunity and long-term immunological memory in mouse tumor models. The data highlight the advantages of SYNB1891 for the potential treatment of cancers that are resistant to current immunotherapy approaches.

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"Our goal is to design Synthetic Biotic medicines that enable us to expand the benefits of immunotherapy broadly across tumor types," said Aoife Brennan, M.B., Ch. B., Synlogic’s president and chief executive officer. "Tumors have multiple mechanisms to evade the immune system and our Synthetic Biotic platform is uniquely suited to address this area of unmet medical need given our ability to engineer multiple mechanisms in a single biotic. We are excited to move this first program into the clinic."

"Our Synthetic Biotic drug candidate, SYNB1891, enabled dual activation of the innate immune system via both the bacterial chassis and its STING agonist payload in mouse tumor models," said Jose Lora, Ph.D., Synlogic’s vice president of research. "We have engineered a non-pathogenic bacterial strain to deliver immunostimulatory molecules directly into the tumor microenvironment, which has the potential to induce a local immune response and establish systemic immunity while minimizing systemic toxicity."

In a presentation, Development of a STING Agonist-producing Synthetic Biotic Medicine to Activate Innate and Adaptive Immunity and Drive Antitumor Immune Responses, to be given at the SITC (Free SITC Whitepaper) 33rd Annual Meeting on Friday, November 9, 2018, Synlogic scientists will describe an engineered strain of E. coli Nissle, (SYNB1891) that produces cyclic di-AMP (CDA) which stimulates the STING pathway. Recent studies have demonstrated that activation of the STimulator of INterferon Genes (STING) pathway can play a critical role in the initiation of an anti-tumor immune response via activation of antigen presenting cells (APCs) and presentation of tumor antigens. SYNB1891 can be delivered directly into the tumor where it remains active for several days to stimulate a local immune response. When the bacteria are engulfed by APCs within the tumor, the STING pathway is activated within the cell resulting in a type I IFN response. In addition, the bacterial chassis used in Synlogic’s Synthetic Biotic approach is believed to be able to stimulate the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response.

In preclinical studies that will be presented at SITC (Free SITC Whitepaper) 2018, Synlogic has demonstrated that:

In vitro, SYNB1891 produces biologically-relevant levels of CDA, activating both mouse and human APCs
In a reporter assay, SYNB1891 induced production of higher levels of type I IFN protein compared to naked CDA, and in human primary APCs SYNB1891 treatment resulted in significantly higher expression of genes encoding type I IFN-beta and IL-6, when compared to naked STING-agonist treatment
Treatment with the un-engineered E. coli Nissle (SYNB) alone resulted in increased tumoral innate cytokine levels and anti-tumor activity, demonstrating that the bacterial chassis itself triggers complementary innate immunity pathways which are further potentiated by arming the bacteria with STING agonist
SYNB1891 prototype-treated tumors demonstrate upregulation of an inflammation-related gene signature
SYNB1891 prototype treatment of B16.F10 melanoma tumors resulted in an early rise in innate-immune cytokines and at later times resulted in T cell activation in tumors and tumor-draining lymph nodes
These pharmacodynamic changes correlated with robust anti-tumor responses and complete tumor regressions
Mice that exhibited complete regression of tumors in response to SYNB1891 prototype treatment demonstrated long-term immunological memory when re-challenged with tumor cells >40 days post tumor eradication
Investor and Analyst Event Details
On Saturday, November 10, 2018, at the SITC (Free SITC Whitepaper) 33rd Annual meeting in Washington D.C., Synlogic will also host an Investor and Analyst Event. The program will feature commentary from experts Filip Janku, M.D., Ph.D., Associate Professor in the Department of Investigational Cancer Therapeutics and Center Medical Director for the Clinical and Translational Research Center at MD Anderson Cancer Center, and Dmitriy Zamarin, M.D., Ph.D., Assistant Attending Physician in Gynecologic Medical Oncology and Immunotherapeutics Services at the Memorial Sloan Kettering Cancer Center who will discuss the unmet medical need and current landscape in immuno-oncology, as well as company representatives who will outline Synlogic’s plans for clinical development of its clinical candidate, SYNB1891.

Presentations will begin at 12:30 pm, until 2:00 pm. ET, on Saturday, November 10, 2018.

The event will be webcast live and available via a link on the company’s website in the Events Calendar in the Investors and Media section.

Aclaris Therapeutics Reports Third Quarter 2018 Financial Results and Provides Update on Clinical and Commercial Developments

On November 6, 2018 Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led biopharmaceutical company focused on identifying, developing, and commercializing innovative therapies to address significant unmet needs in aesthetic and medical dermatology and immunology, reported financial results for the third quarter of 2018 and provided an update on its clinical development and commercial programs (Press release, Aclaris Therapeutics, NOV 6, 2018, View Source [SID1234530841]).

In October, Aclaris entered into a definitive asset purchase agreement with Allergan Sales, LLC to acquire worldwide rights to RHOFADE (oxymetazoline hydrochloride) cream, 1% and additional intellectual property. The acquisition includes an exclusive license to certain intellectual property for RHOFADE, which is approved in the United States for the topical treatment of persistent facial erythema (redness) associated with rosacea in adults. Aclaris expects this acquisition to close in the fourth quarter of 2018.

During the third quarter of 2018, total net revenue was $1.6 million, which consisted of net sales of ESKATA (hydrogen peroxide) Topical Solution, 40% (w/w) of $0.5 million and contract research revenue of $1.1 million.

In September, Aclaris initiated the Phase 3 program for A-101 45% Topical Solution (A-101 45%) for the treatment of common warts (verruca vulgaris).

Aclaris has completed enrollment in the ongoing AA-201 topical formulation trial of ATI-502 in patients with patchy alopecia areata (AA), a less severe phenotype of AA, data from which is expected in the first half of 2019.

"This is an exciting time for Aclaris. With the anticipated closing of the acquisition of RHOFADE in the fourth quarter, we will take another major step toward establishing ourselves as a fully integrated biopharmaceutical company with multiple commercial products, a robust clinical-stage pipeline and drug discovery engine," said Dr. Neal Walker, President and Chief Executive Officer of Aclaris.

Clinical Pipeline Update:

A-101 45% Topical Solution –

Initiated Phase 3 program (THWART-1 and THWART-2) for the treatment of common warts in September 2018. Topline data are expected in the second half of 2019.

Plan to commence an open-label safety extension trial investigating A-101 45% for the treatment of common warts in 2019.

JAK Inhibitor Trials:

AA-202 Topical –

An ongoing Phase 2 clinical trial of ATI-502, a topical JAK 1/3 inhibitor, for the treatment of AA.

Data from the full cohort of patients expected before year end.

After completing the 28-day portion of the trial, patients entered a 6-month open-label extension during which all continuing patients will receive drug. Treatment period extended in August 2018 for an additional 6 months to allow for full year of drug exposure.

Evidence of hair regrowth in the open-label extension portion of this trial has been observed.

Safety results – generally well-tolerated; no treatment related serious adverse events reported to date.

AUATB-201 Topical –

An ongoing Phase 2 open-label clinical trial of ATI-502 for the topical treatment of AA in Australia.

In this trial, Aclaris is evaluating the safety and efficacy of ATI-502 on the regrowth of eyebrows in patients with AA, including patients with alopecia totalis (AT) and alopecia universalis (AU). Interim update:

12 patients have been enrolled; 5 continue in the trial. Patients will also enroll in a 12 month extension phase of the trial after completing 6 months.

Evidence of eyebrow hair regrowth has been observed in two patients.

Safety results – generally well-tolerated; no treatment-related serious adverse events reported to date.

AA-201 Topical –

Completed enrollment of this ongoing Phase 2 clinical trial of ATI-502 for the topical treatment of AA.

This randomized, double-blinded, parallel-group, vehicle-controlled trial will evaluate the safety, efficacy and dose response of two concentrations of ATI-502 on the regrowth of hair in approximately 120 patients with AA. This trial is being conducted in the United States and data are expected in the first half of 2019.

VITI-201 Topical – Completed enrollment of this ongoing Phase 2 open-label clinical trial of ATI-502 for the topical treatment of vitiligo. This trial will evaluate the safety and efficacy of ATI-502 on the repigmentation of facial skin in 33 patients with vitiligo, and data are expected in 2019.

AGA-201 Topical – Completed enrollment of this ongoing Phase 2 open-label clinical trial of ATI-502 for the topical treatment of androgenetic alopecia (AGA), also known as male/female pattern hair loss. This trial will evaluate the safety and efficacy of ATI-502 on the regrowth of hair in 31 patients with AGA, and data are expected in the first half of 2019.

AD-201 Topical – an ongoing Phase 2 open-label clinical trial of ATI-502 in patients with atopic dermatitis (AD). This trial will evaluate the safety and efficacy of ATI-502 applied twice daily to affected skin for four weeks in approximately 30 adult patients with moderate-to-severe AD, and data are expected in mid-2019.

AUAT-201 Oral – an ongoing Phase 2 dose ranging trial of ATI-501, an oral JAK 1/3 inhibitor for the treatment of AA. This randomized, double-blinded, parallel-group, placebo-controlled trial will evaluate the safety, efficacy and dose response of three concentrations of ATI-501 on the regrowth of hair in approximately 80 patients with AA, and data are expected in the second half of 2019.

ATI-450 (MK-2 Inhibitor) – Investigational New Drug application on track for submission to the FDA in mid-2019.

Recent Corporate Highlights:

In October, Aclaris entered into a Loan and Security Agreement with Oxford Finance LLC. The Loan Agreement provides for up to $65 million in term loans. Of the $65 million, Aclaris borrowed $30 million on October 31, 2018. The remaining $35 million will become available for draw beginning on the closing date of the RHOFADE acquisition and ending on the earlier of March 31, 2019 or an event of default.

In October, Aclaris closed an underwritten public offering of 9,941,750 shares of Aclaris’ common stock at a price to the public of $10.75 per share, which includes the full exercise of the underwriters’ option to purchase 1,296,750 additional shares, for total gross proceeds of $106.9 million. Aclaris paid underwriting discounts and commissions of $6.4 million. All of the common stock in the offering was sold by Aclaris.

Issued US Patent # 10,098,910 – In October, Aclaris was issued a U.S. patent with 18 claims directed to an applicator containing a formulation of high concentration hydrogen peroxide and methods of using such an applicator to treat seborrheic keratosis (SK), warts and other indications, which is scheduled to expire in 2035. Orange Book listed.

Co-authored an article titled: "Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss" in the journal Cancer Research. ATI-450, an investigational drug, is a selective inhibitor of p38 mitogen-activated protein kinase-activated protein kinase 2 (p38MAPK/MK2) interface and an attractive candidate for stromal-targeted therapy.

Commercial Update:

Over 1,050 ESKATA accounts opened to date.

Sales force focused on driving clinical and business integration in existing ESKATA accounts in addition to expanding account base.

National DTC campaign initiated on October 1.

Financial Highlights:

Third Quarter 2018 Financial Results

For the quarter ended September 30, 2018, total net revenues were $1.6 million, which consisted of net sales of ESKATA of $0.5 million and contract research revenue of $1.1 million, compared to $0.7 million for the quarter ended September 30, 2017, all of which was contract research revenue. For the nine months ended September 30, 2018, total net revenues were $6.4 million, which consisted of net sales of ESKATA of $2.0 million, contract research revenue of $3.4 million, and other revenue of $1.0 million, compared to $0.7 million for the nine months ended September 30, 2017, all of which was contract research revenue. Cost of revenues for the quarter and nine months ended September 30, 2018 were $1.2 million and $3.3 million, respectively, compared to $0.5 million for both the quarter and nine months ended September 30, 2017.

For the quarter ended September 30, 2018, total operating expenses were $33.9 million, compared to $19.0 million for the third quarter of 2017. For the nine months ended September 30, 2018, total operating expenses were $99.5 million, compared to $47.2 million for the same period in 2017.

Research and development (R&D) expenses for the quarter and nine months ended September 30, 2018 were $15.9 million and $43.5 million, respectively, compared to $10.9 million and $26.6 million, for the same periods of 2017. The increases of $5.0 million and $16.9 million were mainly the result of the expansion of Aclaris’ JAK inhibitor and common wart programs, as multiple Phase 2 trials of ATI-501 and ATI-502 and Phase 3 trials of A-101 45% are ongoing in 2018. There were also increases in medical affairs activities related to ESKATA and costs associated with drug discovery programs as a result of the acquisition of Confluence in August 2017. Personnel expenses, including stock-based compensation, increased due to increased headcount to support these programs and as a result of the acquisition of Confluence in August 2017. These increases were offset by a decrease in costs related to the development of ESKATA leading to Aclaris’ NDA submission in February 2017 following the completion of the clinical trials.

Sales and marketing (S&M) expenses for the quarter and nine months ended September 30, 2018 were $11.4 million and $35.0 million, respectively, compared to $3.6 million and $7.2 million, for the same periods of 2017. The increases of $7.8 million and $27.8 million were mainly the result of increases in direct marketing and professional fees, as well as other commercial expenses incurred to support the launch of ESKATA in May 2018. Personnel

expenses, including stock-based compensation, increased as Aclaris completed the hiring of its field sales force in the first quarter of 2018.

General and administrative (G&A) expenses for the quarter and nine months ended September 30, 2018 were $6.6 million and $21.0 million, respectively, compared to $4.6 million and $13.4 million, for the same periods of 2017. The increases of $2.0 million and $7.6 million were mainly the result of higher personnel expenses, including stock-based compensation, due to increased headcount to support the commercial launch of ESKATA, and as a result of the acquisition of Confluence in August 2017. G&A expenses for the nine months ended September 30, 2018 also included a $1.5 million ESKATA-related milestone payment, whereas the nine months ended September 30, 2017 included a $1.0 million ESKATA-related milestone payment.

For the quarter ended September 30, 2018, net loss was $32.7 million, or $1.06 per basic and diluted share, as compared to $18.2 million, or $0.63 per basic and diluted share, for the third quarter of 2017. For the nine months ended September 30, 2018, net loss was $94.2 million, or $3.04 per basic and diluted share, as compared to $45.6 million, or $1.68 per basic and diluted share, for the same period of 2017.

Liquidity and Capital Resources

As of September 30, 2018, Aclaris had aggregate cash, cash equivalents and marketable securities of $134.3 million compared to $208.9 million as of December 31, 2017.

Aclaris anticipates that its cash, cash equivalents and marketable securities balances, including the proceeds from the public offering of common stock in October and the initial drawdown from the loan facility with Oxford, will be sufficient to fund its operations into the second half of 2020, without giving effect to any potential new business development transactions or financing activities.

2018 Financial Outlook

Aclaris has updated its expected 2018 GAAP R&D expenses to be in the range of $62 to $64 million, including estimated stock-based compensation of $7 million.

Aclaris updated its expected 2018 GAAP selling, general and administrative (SG&A) expenses, which combine its Sales and marketing and General and administrative line items, to be in the range of $77 to $79 million, including estimated stock-based compensation of $14 million.

Company to Host Conference Call

Management will conduct a conference call at 5:00 PM ET today to discuss Aclaris’ financial results and provide a general business update. The conference call will be webcast live over the Internet and can be accessed by logging on to the "Investors" page of the Aclaris Therapeutics website, www.aclaristx.com, prior to the event. A replay of the webcast will be archived on the Aclaris Therapeutics website for 30 days following the call.

Agenus Reports Third Quarter 2018 Financial Results and Provides Corporate Update

On November 6, 2018 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, cancer vaccines and adoptive cell therapies1, provided a corporate update and reported financial results for the third quarter of 2018 (Press release, Agenus, NOV 6, 2018, View Source [SID1234530830]).

"We have made substantial operational advances. These are unprecedented for a company of our size but also for the field of I-O," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "We have shown that our CTLA-4 and PD-1 antibodies are active in the clinic with clinical benefit seen in the majority of the more than 130 patients treated. Recently we met with the FDA to confirm our clinical path to a BLA filing. In addition to these, our discovery engines have produced 4 INDs which have been filed this year, including our next generation CTLA-4. We plan to finish the year with two additional IND filing of first-in-class bispecifics. We also expect the closure of at least one corporate partnership transaction by year end."

Key operational and business updates

Operational Achievements:
PD-1 & CTLA-4 show clinical benefit in majority of patients across multiple solid tumors, including cervical cancer
Clinical benefit rate of 68% and 63% for AGEN2034 & AGEN18842
FDA meeting confirms path to BLA filing for lead molecules
Three trials are ongoing to leverage accelerated approval pathways
New discoveries advance to clinic
Four INDs filed in 2018, including Next-Gen CTLA-4, AGEN1181
Two First-in-class bispecific IND filings on track by year end
2018 Payment milestones triggered in partnerships with Incyte, Merck
LAG-3 (INCAGN02385) and TIM-3 (INCAGN02390) in the clinic with milestones received and to be received in Q4
Undisclosed target with Merck entered clinic also generating a milestone payment
Sales of GSK’s Shingrix, containing QS-21 Stimulon, have significantly exceeded earlier sales projections
Partnership discussions on track to be concluded by year end
Manufacturing Speed and Innovation driving advances to the clinic:
Setting industry records for clinical & pivotal grade material
3-5x faster for lead compounds
First-in-class bispecific, AGEN1223, manufactured at scale in <2 months
AgenTus Cell Therapy Business:
Lead identified for IND filing; private financing and plans for IPO underway
Third Quarter 2018 Financial Results

Cash and cash equivalents were $46.3 million at the end of the 3rd quarter compared to $43.2 million and $60.2 million at June 30, 2018 and December 31, 2017 respectively. Subsequent to the end of 3rd quarter, Agenus announced the completion of a private financing of $40 million with a single investor netting the company approximately $39.9 million.

For the third quarter ended September 30, 2018, we reported a net loss of $34 million or $0.29 per share compared to a net loss for same period in 2017 of $37 million, or $0.37 per share. In the third quarter, we recognized revenue of $13 million which includes a milestone achieved and non-cash royalties earned.

For the nine months ended September 30, 2018, we had a net reported loss of $113 million or $1.04 per share compared to a net reported loss for the same period in 2017 of $86 million or $0.88 per share. The increased net loss reflects reduced revenue during 2018 due to accelerated milestones received during 2017 from Incyte and the 2018 loss on early extinguishment of debt.

Conference Call, Webcast and Prepared Statement Information

Conference Call Information:

Date: Tuesday November 6, 2018

Time: 8:30 a.m. ET

Domestic Dial-in Number: (844) 492-3727

International Dial-in Number: (412) 317-5118

Conference ID: Agenus

Live Webcast: accessible from the Company’s website at View Source or with this link View Source

A replay will be available on the Company’s website approximately two hours after the call and will remain available for 90 days.

Protagonist Therapeutics Reports Third Quarter 2018 Financial Results and Provides Corporate Update

On November 6, 2018 Protagonist Therapeutics, Inc. (Nasdaq:PTGX) reported its financial results for the third quarter ended September 30, 2018, and provided a corporate update on its clinical development programs (Press release, Protagonist, NOV 6, 2018, View Source [SID1234530829]).

"We are pleased to report continued progress from each of the three clinical programs evaluating differentiated and novel therapeutics enabled by our proprietary peptide engineering platform," commented Dinesh V. Patel, Ph.D., Protagonist President and Chief Executive Officer. "We recently presented safety and efficacy data from the Phase 2 PROPEL study. Notably, these data show dose-dependent histologic remission in ulcerative colitis patients. The cumulative data for PTG-100, which now includes clinical, endoscopic, histologic and biomarker data, is supportive of the GI-restricted, oral targeted therapy approach for potential treatment of inflammatory bowel diseases."

"In addition, we recently announced successful completion of the Phase 1 clinical trial of the oral interleukin-23 receptor antagonist PTG-200. We are working closely with our partner Janssen Biotech to support the U.S. IND filing for a Phase 2 Crohn’s trial in the coming months."

"Our hepcidin mimetic PTG-300 is on track for initiation of an open label, global, phase 2 trial in beta-thalassemia patients by year end. We are encouraged to note that PTG-300 now has Orphan Drug Designation both from the U.S. FDA and European Medicines agency, as well as Fast Track designation from the U.S. FDA for beta-thalassemia."

Product Development Update:

PTG-100

· Clinical data from the PROPEL Study presented at the recent United European Gastroenterology Week demonstrated that treatment with PTG-100, an oral, gut-restricted alpha-4-beta-7 integrin antagonist peptide, was well tolerated and associated with higher rates of clinical remission relative to placebo.

· The dose-dependent increase in rates of histologic remission, the blood biomarker data and topline safety data presented at the meeting expand upon the clinical remission and endoscopic response results announced previously in August 2018 that involved an independent, blinded re-read of endoscopies and had demonstrated signals of clinical efficacy.

· The totality of the data from the Phase 2 PROPEL study in UC patients provides first evidence of safety and clinical efficacy with an oral alpha-4-beta-7-integrin specific antagonist agent and supports further development of PTG-100.

PTG-200

· The Phase 1 study of PTG-200, an oral peptide IL-23 receptor antagonist partnered with Janssen Biotech, was successfully completed. Top-line results from this randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study in 80 normal healthy volunteers demonstrated that PTG-200 treatment was well tolerated, with no serious adverse events or dose-limiting toxicities observed. Pharmacokinetic and pharmacodynamic parameters were consistent with the gastrointestinal-restricted design of PTG-200.

· Results from this study provide the first clinical data in support of PTG-200 and creates a path forward for its evaluation as a potential first-in-class oral IL-23 pathway based therapeutic for treatment of IBD.

·Protagonist and Janssen Biotech are working towards filing a U.S. IND in the coming months to support a Phase 2 clinical study in Crohn’s disease patients.

PTG-300

·The Company remains on track to initiate a global Phase 2 clinical trial in beta-thalassemia patients in the fourth quarter of 2018.

· The U.S. FDA granted Fast Track Designation to PTG-300 for the treatment of chronic anemia due to ineffective erythropoiesis in patients with beta-thalassemia. This designation will facilitate the future development and expedite the review process of PTG-300.

· The European Medicines Agency granted Orphan Drug Designation to PTG-300 in the treatment of beta-thalassemia. Orphan drug designation from the US FDA had been previously granted for PTG-300 for potential treatment of beta-thalassemia. An orphan designation provides regulatory and financial incentives for development as well as certain benefits upon regulatory approval, if received.

Corporate Update — Financing:

· Protagonist announced the completion of a financing with investors including BVF Partners L.P. and their affiliates for gross proceeds of $22 million in August 2018. This enables the company to fund the development of its multiple clinical assets in diverse disease indications addressing unmet medical needs.

Financial Results

Protagonist reported a net loss of $8.7 million and $25.1 million, respectively, for the third quarter and first nine months of 2018, as compared to a net loss of $4.8 million and $33.9 million, respectively, for the same periods of 2017. The increase in net loss for the third quarter of 2018 as compared to the prior year period was driven primarily by a decrease in revenue under the Janssen Collaboration Agreement related to proportional performance as measured by actual costs incurred as a percentage of budgeted costs, and increases in research and development (R&D) and general and administrative (G&A) expenses. The decrease in net loss for the first nine months of 2018 as compared to the prior year period was driven primarily by an increase in revenue under the Janssen Collaboration Agreement, which became effective in the third quarter of 2017, partially offset by increases in R&D and G&A expenses. The net loss for the third quarter and first nine months of 2018 includes non-cash stock-based compensation of $2.0 million and $4.8 million, respectively, as compared to $1.2 million and $3.1 million, respectively, for the same periods of 2017.

R&D expenses for the third quarter and first nine months of 2018 were $12.1 million and $45.2 million, respectively, as compared to $11.2 million and $34.5 million, respectively, for the same periods of 2017. The increases in R&D expenses were primarily due to costs related to contract manufacturing and the preparation for and conduct of clinical trials for our product candidates. R&D expenses for the third quarter and first nine months of 2018 included increases in salaries and employee-related expenses due to an increase in R&D personnel.

G&A expenses for the third quarter and first nine months of 2018 were $3.4 million and $10.2 million, respectively, as compared to $2.6 million and $8.7 million, respectively, for the same periods of 2017. The increases in G&A expenses were primarily due to increases in salaries and employee-related expenses to support the growth of our operations.

Protagonist ended the third quarter with $138.5 million in cash, cash equivalents and investments. The company expects to have sufficient financial resources to fund operations to mid-2020.

BioCryst Reports Third Quarter 2018 Financial Results

On November 6, 2018 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the third quarter ended September 30, 2018 (Press release, BioCryst Pharmaceuticals, NOV 6, 2018, View Source [SID1234530828]).

"With enrollment in APeX-2 complete, and the successful results from ZENITH-1, we are excited with the momentum that is building towards meeting the urgent demand of HAE patients for an oral therapy option to prevent and treat their attacks," said Jon Stonehouse, president and chief executive officer of BioCryst.

"We have many significant milestones lined up over the next several months and we are focused on delivering high quality APeX-2 data in the second quarter of 2019, filing our New Drug Application (NDA) for BCX7353 in the fourth quarter of 2019 and advancing at least one additional pipeline program into the clinic in the first half of the year," Stonehouse added.

Upcoming Key Milestones:

Complete the 250 mg and 500 mg dose cohorts of the ZENITH-1 clinical trial for acute treatment of hereditary angioedema (HAE) attacks with BCX7353 (Q1 2019)

Meet with U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for input on the design of a Phase 3 clinical trial of BCX7353 for acute treatment of HAE attacks, and commence the Phase 3 trial (Summer 2019)

Report results from the APeX-2 clinical trial (Q2 2019)

Advance at least one preclinical program into the clinic and begin the Phase 1 clinical trial (1H 2019)

File NDA for BCX7353 for prevention of HAE attacks with FDA (Q4 2019)

Third Quarter 2018 Financial Results

For the three months ended September 30, 2018, total revenues were $1.5 million, compared to $8.8 million in the third quarter of 2017. The decrease was primarily associated with two infrequent 2017 events that did not recur in 2018. A $5.0 million milestone payment associated with the FDA approval of a supplemental New Drug Application (sNDA) for RAPIVAB (peramivir injection), extending its availability for the treatment of acute uncomplicated influenza to pediatric patients two years and older, and the recognition of $1.5 million of peramivir product sales to the company’s commercial partner, Green Cross Corporation.

Research and development (R&D) expenses for the third quarter of 2018 increased to $22.0 million from $17.5 million in the third quarter of 2017, primarily due to increased spending on the company’s HAE and preclinical programs.

General and administrative (G&A) expenses for the third quarter of 2018 increased to $7.9 million, compared to $3.3 million in the third quarter of 2017. The increase was primarily due to merger-related costs associated with the company’s terminated merger with Idera Pharmaceuticals, Inc. (Idera).

Interest expense was $2.3 million in the third quarter of 2018, compared to $2.1 million in the third quarter of 2017.

Net loss for the third quarter of 2018 was $29.6 million, or $0.28 per share, compared to a net loss of $15.1 million, or $0.18 per share, for the third quarter 2017.

Cash, cash equivalents and investments totaled $151.0 million at September 30, 2018, and reflect a decrease from $159.0 million at December 31, 2017. Cash and investments reflect the proceeds from a July 2018 enhancement to our credit facility and an August 2018 public equity offering, offset by normal operating expenses and merger related costs incurred in the nine-month period. Net operating cash use for the third quarter 2018 was $29.4 million, and for the first nine months of 2018 was $70.7 million.

Year to Date 2018 Financial Results

For the nine months ended September 30, 2018, total revenues were $17.9 million, compared to $21.3 million in the first nine months of 2017. The decrease in revenue was primarily associated with infrequent revenue events that occurred in 2017 that did not recur in 2018, as well as a decrease of revenue from galidesivir development under U.S. Government contracts. Those 2017 events were the recognition of $4.1 million of royalty revenue from Japanese government stockpiling of RAPIACTA and the recognition of $1.5 million of peramivir product sales to the company’s commercial partner, Green Cross Corporation. In the nine-month periods, there was a $5.0 million milestone and $7.0 million of deferred revenue both associated with the EMA’s approval of peramivir (ALPIVAB) recognized in the second quarter of 2018, and two infrequent events that occurred in the third quarter of 2017, as discussed in the third quarter commentary above.

R&D expenses in the first nine months of 2018 increased to $61.5 million from $50.0 million in the first nine months of 2017, primarily due to increased spending on our HAE and preclinical programs. These increases were partially offset by a decrease in the company’s peramivir and galidesivir development spending in 2018.

G&A expenses for the first nine months of 2018 increased to $25.0 million, compared to $9.2 million in the first nine months of 2017. The increase was primarily due to approximately $11 million of merger-related costs associated with the company’s terminated merger with Idera and a $4.9 million reserve for collectability of the EMA approval milestone of peramivir.

Interest expense was $6.8 million in the first nine months of 2018, compared to $6.3 million in the first nine months of 2017.

Net loss for the first nine months of 2018 was $73.8 million, or $0.73 per share, compared to a net loss of $46.2 million, or $0.58 per share, for the first nine months of 2017.

Third Quarter 2018 Corporate Developments

On September 17, 2018, BioCryst announced that the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, had awarded BioCryst an additional $3.5 million to support clinical trials of galidesivir in patients with yellow fever.

On September 6, 2018, BioCryst announced that the Centers for Disease Control and Prevention (CDC) had awarded BioCryst a $34.7 million contract for the procurement of up to 50,000 doses of BioCryst’s approved antiviral influenza therapy, RAPIVAB (peramivir injection) over a five-year period.

On September 4, 2018, BioCryst announced initial results from the ZENITH-1 trial showing that a single 750 mg oral dose of BCX7353 was well tolerated and superior to placebo (p<0.05) against the majority of efficacy endpoints evaluated in HAE patients suffering an acute attack.

On August 6, 2018, BioCryst announced it has received Fast Track Designation by the FDA for BCX7353 for the prevention of angioedema attacks in patients with hereditary angioedema.

On August 6, 2018, BioCryst announced the full exercise of the underwriters’ option to purchase additional shares and the completion of its public offering resulting in the sale of 10,454,546 shares of its common stock at a price of $5.50 per share. The net proceeds from this offering were approximately $53.4 million, after deducting underwriting discounts and commissions and other estimated offering expenses.

On July 25, 2018, BioCryst announced that results from the Phase 2, APeX-1 trial of BCX7353 for the prevention of attacks in patients with HAE were published in the July 26th issue of The New England Journal of Medicine.

On July 20, 2018, BioCryst entered into a $30 million secured loan facility with MidCap Financial Trust as administrative agent and lender (MidCap), pursuant to the terms and conditions of that certain Amended and Restated Credit and Security Agreement. The Credit Agreement replaces the Credit and Security Agreement dated as of September 23, 2016.

On July 10, 2018, BioCryst announced that it had terminated the previously announced merger agreement with Idera following the company’s stockholders’ failure to approve the adoption of the merger agreement. Pursuant to the merger agreement, the company reimbursed Idera $6 million in July 2018.
Financial Outlook for 2018

Based upon development plans, merger-related incurred costs from the terminated merger agreement with Idera and awarded government contracts, BioCryst continues to expect its previously issued 2018 financial outlook to be appropriate, with net operating cash use to be in the range of $85 to $105 million, and its 2018 operating expenses to be in the range of $90 to $110 million. The company’s operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the company’s stock, as well as by the vesting of the company’s outstanding performance-based stock options.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID #9090479. A live webcast of the call and slides will be available online at the investors section of the company website at www.biocryst.com. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 9090479.

About BCX7353

Discovered by BioCryst, BCX7353 is a novel, oral, once-daily, selective inhibitor of plasma kallikrein currently in development for the prevention and treatment of angioedema attacks in patients diagnosed with HAE. BCX7353 was generally safe and well tolerated in the Phase 2 APeX-1 clinical trial. BioCryst is currently conducting the Phase 3 APeX-2 clinical trial and the long-term safety APeX-S clinical trial, both evaluating two dosage strengths of BCX7353 administered orally once-daily as a preventive treatment to reduce the frequency of attacks in patients with HAE. BioCryst is also conducting the ZENITH-1 clinical trial. ZENITH-1 is a proof-of-concept Phase 2 clinical trial testing an oral liquid formulation of BCX7353 for the treatment of acute angioedema attacks.