On August 8, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported financial results and business highlights for the second quarter ended June 30, 2019 (Press release, Tocagen, AUG 8, 2019, View Source [SID1234538469]).

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"We are making excellent progress towards achieving our corporate objectives for the year. We are focused on providing the final analysis of our pivotal Phase 3 Toca 5 trial and preparing for a potential rolling BLA filing with FDA. The Toca 5 trial involving 403 patients with recurrent brain cancer will generate an extensive data set and holds promise to shape the treatment of these patients with a novel, multi-modality cancer-selective gene therapy in combination with surgery," said Marty Duvall, chief executive officer of Tocagen. "We also continue to execute our life cycle strategy for Toca 511 & Toca FC with the submission to FDA of a draft protocol for the planned Phase 2/3 trial of Toca 511 & Toca FC in patients with newly diagnosed glioblastoma sponsored by NRG Oncology, which remains on track to activate by the end of 2019. In addition, we recently advanced plans to evaluate Toca 511 & Toca FC in non-CNS tumors with a trial for patients with non-muscle invasive bladder cancer, which is also expected to initiate by the end of the year."

Second Quarter 2019 and Recent Highlights
2019 Corporate Milestones

Toca 5 second interim analysis completed: On May 21, Tocagen announced the pivotal Toca 5 Phase 3 clinical trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma (HGG) would continue without modification following a planned second interim analysis conducted by an Independent Data Monitoring Committee. Tocagen expects to report the final analysis of the Toca 5 trial this year.
Progress related to Toca 511 & Toca FC BLA and commercialization: With Breakthrough Therapy Designation, Tocagen is preparing for the initiation of a rolling biologics license application, pending positive data from Toca 5. The company’s launch readiness activities span disease state awareness, branding activities, distribution, channel and pricing strategies, payor and key opinion leader engagements and beginning to build the commercial and medical affairs infrastructure and team.
NRG Oncology trial in newly diagnosed glioblastoma (ndGBM) proceeding: The Phase 2/3 trial to be conducted by NRG Oncology (NRG-BN006) evaluating Toca 511 & Toca FC in combination with standard of care (SOC) versus SOC alone in patients with ndGBM is proceeding towards initiation by year-end 2019.
Planned reporting of updated Toca 6 data: Tocagen remains on track to provide updated data including immune modulation data from this Phase 1b trial in advanced solid tumors at an upcoming scientific congress this year.
Activation of Toca 8 clinical program in bladder cancer: As part of Tocagen’s life cycle plans for Toca 511 & Toca FC and based on encouraging preclinical data and results from the Toca 6 trial, the company plans to initiate a Phase 1b trial, Toca 8, in non-muscle invasive bladder cancer (NMIBC) in the second half of this year.
Preclinical research publication: Tocagen’s most recent preclinical research paper described the use of Tocagen’s retroviral replicating platform to successfully deliver a single chain monoclonal antibody fragment against PD-L1 resulting in durable and highly selective anti-tumor activity compared to systemically administered anti-PD-L1 or anti-PD-1 monoclonal antibodies.
Second Quarter 2019 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $12.0 million for the quarter ended June 30, 2019, compared to $12.8 million for the quarter ended June 30, 2018. The R&D expenses in both periods were primarily driven by costs to support the Toca 5 trial and manufacturing of drug product. The decrease quarter over quarter is primarily due to reduced clinical trial costs in 2019 compared to 2018 as the Toca 5 trial nears completion.

General and Administrative (G&A) Expenses: G&A expenses were $4.9 million for the quarter ended June 30, 2019, compared to $2.6 million for the quarter ended June 30, 2018. The increase in G&A expenses was primarily due to higher personnel and related costs, including stock-based compensation, due to additional headcount and increased contracted services to support commercial readiness activities.

Net Loss: Net loss was $17.1 million, or $0.72 per common share (basic and diluted), for the quarter ended June 30, 2019, compared to a net loss of $16.1 million, or $0.81 per common share (basic and diluted), for the quarter ended June 30, 2018. The 2019 calculation is based on 23.7 million average common shares outstanding for the second quarter of 2019, compared to 19.9 million average common shares outstanding for the second quarter of 2018.

2019 Six-Month Results

R&D Expenses: R&D expenses were $24.4 million for the six months ended June 30, 2019 compared to $23.2 million for the six months ended June 30, 2018. The increase in R&D expenses for the six months ended June 30, 2019 primarily reflect increased personnel and related costs to support the Toca 5 clinical trial as well as manufacturing and other activities to support the potential commencement of a regulatory filing later this year following the completion of the study.

G&A Expenses: G&A expenses were $9.3 million for the six months ended June 30, 2019 compared to $5.0 million for the first six months ended June 30, 2018, with the increase primarily driven by higher personnel and related costs, including stock-based compensation, due to additional headcount and increased contracted services to support commercial readiness activities.

Net Loss: Net loss for the first six months ended June 30, 2019 was $34.2 million, or $1.46 per common share (basic and diluted), compared to a net loss of $29.0 million, or $1.45 per common share (basic and diluted), for the six months ended June 30, 2018. This calculation is based on 23.4 million average common shares outstanding for the six months ended June 30, 2019, compared to 19.9 million average shares outstanding for the same period in 2018.

Cash Position
Cash, cash equivalents and marketable securities were $68.3 million at June 30, 2019 compared to $96.1 million at December 31, 2018.

About Toca 511 & Toca FC
Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

On August 8, 2019 BioLife Solutions, Inc. (NASDAQ: BLFS) ("BioLife" or the "Company"), a leading developer and supplier of a portfolio of best-in-class bioproduction tools for cell and gene therapies, reported financial results and operational highlights for the three and six months ended June 30, 2019 (Press release, BioLife Science, AUG 8, 2019, View Source [SID1234538468]).

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Revenue from biopreservation media and automated thaw product sales for the second quarter of 2019 reached a record of $6.7 million, an increase of 29% compared with the second quarter of 2018. For the first half of 2019 revenue totaled $12.5 million, representing an increase of 39% compared with the prior-year period. Product revenue growth for both periods was driven by sales of CryoStor and HypoThermosol biopreservation media and the recently acquired ThawSTAR automated thaw products to the high-growth cell and gene therapy market.

Mike Rice, BioLife President & CEO, commented, "Throughout the second quarter, we demonstrated our ability to efficiently manage our business during a sustained period of rapid growth. Demand for our proprietary biopreservation media products continues to be strong from new and existing customers. During the quarter we received 14 new cross-reference requests for our FDA master files from cell and gene therapy companies who intend to use CryoStor and/or HypoThermosol in upcoming clinical trials. Based on these new requests, direct customer forecasts and anticipated demand from our worldwide network of distributors, we are optimistic about how the business will perform for the balance of 2019.

"We also realized strong initial demand for automated thaw products in our first full quarter following the acquisition of Astero Bio, with 39 new customer orders. Of note, most of these customers came from the cell and gene therapy segment. We look forward to a Q4 launch of a new ThawSTAR CB automated thaw product for large volume cell and gene therapies to be frozen in cryobags. With respect to SAVSU, we remain bullish on our ability to capture a significant share of the cell and gene therapy cold chain management market. Since January 2019, the evo system has been used in initial shipments by more than 50 cell and gene therapy companies. We look forward to integrating our sales and marketing activities and exhibiting our expanded product portfolio at 10 cell and gene therapy scientific conferences throughout the rest of the year."

Second Quarter 2019 Revenue Highlights

Cell & Gene Therapy Market Segment

Total product revenue: $4.0 million; representing 59% of total revenue with 33% growth over the same period last year.
Shipped initial orders to 51 new biopreservation media customers and 39 new automated thaw products customers, most of which were cell and gene therapy companies in the regenerative medicine market segment.
Received 14 new cross-reference requests for our FDA master files for CryoStor and HypoThermosol.
Worldwide Distributor Network

Product revenue: $2.2 million; representing 33% of total revenue with 31% growth over the same period last year.
Key worldwide distributors include: STEMCELL Technologies, MilliporeSigma, Thermo Fisher and VWR.
Second Quarter and Six Month 2019 Financial Results

BioLife Solutions is presenting various financial metrics under U.S. Generally Accepted Accounting Principles (GAAP) and as adjusted (non-GAAP) to reflect acquisition-related activity. A reconciliation of GAAP to non-GAAP metrics appears at the end of this news release.

Revenue

Total revenue for the second quarter of 2019 increased 29% to $6.7 million compared with $5.2 million for the second quarter of 2018.
Sales of ThawSTAR automated thaw products totaled $374,000 in the second quarter.
Total revenue for the six months ended June 30, 2019 increased 39% to $12.5 million compared with $9.0 million for the first six months of 2018.
Gross Margin

Gross margin (GAAP) for the second quarter of 2019 increased to 70.8% from 70.3% in the second quarter of 2018. Adjusted gross margin (non-GAAP) for the second quarter of 2019 increased to 72.3% from 70.3% in 2018.
Gross margin (GAAP) for the six months ended June 30, 2019 increased to 71.1% from 67.7% for the same period in 2018. Adjusted gross margin (non-GAAP) for the six months ended June 30, 2019 increased to 71.9% from 67.7% in 2018.
Operating Expenses

Operating expenses (GAAP) for the second quarter of 2019 were $3.8 million compared with $2.4 million for the second quarter of 2018. Adjusted operating expenses (non-GAAP) for the second quarter of 2019 were $3.7 million compared with $2.4 million in 2018.
Operating expenses (GAAP) for the six months ended June 30, 2019 were $7.5 million compared with $4.7 million for the same period in 2018. Adjusted operating expenses (non-GAAP) for the six months ended June 30, 2019 were $7.1 million compared with $4.7 million in 2018.
Operating Income

Operating income (GAAP) for the second quarter of 2019 was $919,000 compared with $1.3 million for the second quarter of 2018. Adjusted operating income (non-GAAP) for the second quarter of 2019 was $1.2 million compared with $1.3 million in 2018.
Operating income (GAAP) for the six months ended June 30, 2019 was $1.4 million compared with $1.4 million for the same period in 2018. Adjusted operating income (non-GAAP) for the six months ended June 30, 2019 was $1.9 million compared with $1.4 million in 2018.
Net Income Attributable to Common Stockholders

Net income attributable to common stockholders (GAAP) for the second quarter of 2019 was $838,000 compared with $1.0 million for the second quarter of 2018. Adjusted net income attributable to common stockholders (non-GAAP) for the second quarter of 2019 was $1.1 million compared with $1.0 million in 2018.
Net income attributable to common stockholders (GAAP) for the six months ended June 30, 2019 was $1.3 million compared with $943,000 for the same period in 2018. Adjusted net income attributable to common stockholders (non-GAAP) for the six months ended June 30, 2019 was $1.7 million compared with $943,000 in 2018.
Earnings per Share

Earnings per diluted share (GAAP) for the second quarter of 2019 were $0.03 compared with $0.05 for the second quarter of 2018. Adjusted earnings per diluted share (non-GAAP) for the second quarter of 2019 were $0.04 compared with $0.05 in 2018.
Earnings per diluted share (GAAP) for the six months ended June 30, 2019 were $0.05 compared with $0.05 for the same period in 2018. Adjusted earnings per diluted share (non-GAAP) for the six months ended June 30, 2019 were $0.07 compared with $0.05 in 2018.
EBITDA

EBITDA, a non-GAAP measurement, for the second quarter of 2019 was $917,000 compared with $1.2 million for the second quarter of 2018. Adjusted EBITDA for the second quarter of 2019 was $1.9 million compared with $1.7 million in 2018.
EBITDA, a non-GAAP measurement, for the six months ended June 30, 2019 was $1.3 million compared with $1.3 million for the same period in 2018. Adjusted EBITDA for the six months ended June 30, 2019 was $3.3 million compared with $2.3 million in 2018.
Cash

Cash and cash equivalents as of June 30, 2019 were $19.6 million compared with $30.7 million as of December 31, 2018. The decrease reflects $12.5 million in cash consideration paid in conjunction with the acquisition of Astero Bio Corporation, which closed in early April.
Roderick de Greef, BioLife Chief Financial Officer, remarked, "In addition to successfully integrating Astero’s operations during the second quarter, our financial results at all levels remained strong."

2019 Financial Guidance

Management updated 2019 financial guidance to include contributions from Astero (beginning April 1) and SAVSU (beginning August 8), as follows:

Total revenue of $27.5 million to $30.5 million, representing growth of 39% to 55% over 2018.
Gross margin is expected to be in a range of 69% to 70% on a GAAP and non-GAAP basis, compared with 69% in 2018.
Operating expenses on a GAAP basis ranging from $18.5 to $19.5 million, up from previous guidance of $15.5 to $16.5 million as a result of acquisition costs, amortization of intangible assets and the addition of SAVSU related operating expenses. Adjusted operating expenses (non-GAAP) ranging from $17 to $18 million.
Full-year positive adjusted operating income, adjusted net income and adjusted EBITDA.
Conference Call & Webcast

The Company will host a conference call and live webcast at 4:30 p.m. ET this afternoon. To access the live webcast, please go to www.biolifesolutions.com/earnings/. Alternatively, you may access the live conference call by dialing (844) 825-0512 (U.S. & Canada) or (315) 625-6880 (International) with the following Conference ID: 1368786. A webcast replay will be available approximately two hours after the call and will be archived on www.biolifesolutions.com for 90 days.

On August 8, 2019 Nevro Corp. (NYSE: NVRO), a global medical device company that is providing innovative, evidence-based solutions for the treatment of chronic pain, reported financial results for the second quarter ended June 30, 2019 (Press release, Nevro, AUG 8, 2019, View Source [SID1234538467]).

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Revenue for the second quarter of 2019 was $93.6 million, a 3% decrease compared to $96.1 million during the prior year period. U.S. revenue for the second quarter of 2019 was $78.1 million, a 2% decrease compared to $79.9 million in the prior year period. The year-over-year decrease in U.S. revenue was primarily driven by the impact of customer destocking associated with the Company’s previously announced decision to alter its practice regarding certain high-volume product orders. International revenue was $15.5 million compared to $16.2 million in the prior year period. This represents a 4% decrease on an as-reported basis and a 2% increase on a constant currency basis.

"Our second quarter 2019 financial results demonstrate sequential improvement across the board, as well as some encouraging early signs of progress in our commercial execution, including patient treatment activity with our customers. In the U.S., we saw a year-over-year increase in patient trial procedures of 15%, while permanent implant procedures grew 10% over the prior year period," said D. Keith Grossman, Chairman, CEO and President. "I remain confident that as we continue to refine our commercial strategies and execution, prepare for our upcoming new product launches and drive interest in HF10 therapy, we will be well-positioned to enter our next phase of growth as we move into late 2019 and enter 2020."

Gross profit for the second quarter of 2019 was $63.9 million, a 6% decrease compared to $67.9 million in the prior year period. Gross margin was 68% in the second quarter of 2019 compared to 71% in the prior year period.

Operating expenses for the second quarter of 2019 were $90.5 million, a 19% increase compared to $76.1 million in the prior year period. The year-over-year increase in operating expenses was primarily driven by U.S. sales and marketing personnel costs, as well as clinical trial-related expenses. Legal expenses associated with patent litigation were $3.9 million for the second quarter of 2019, compared to $5.8 million in the prior year period.

Net loss from operations for the second quarter of 2019 was $26.6 million, compared to $8.2 million in the prior year period.

Cash, cash equivalents and short-term investments totaled $233.9 million as of June 30, 2019. Net cash used during the second quarter of 2019 was $5.7 million and $30.6 million for the six months ended June 30, 2019.

Full Year 2019 Financial Guidance
Nevro currently expects 2019 worldwide revenues to be in the $368 to $374 million range. Gross margin is expected to be in the high 60’s as a percent of revenue.

Webcast and Conference Call Information
Management will host a conference call today beginning at 1:30 p.m. PT / 4:30 p.m. ET. Investors interested in listening to the conference call may do so by dialing (833) 286-5807 in the U.S. or (647) 689-4452 internationally, using Conference ID: 1694716. In addition, a live webcast will be available on the "Investors" section of the company’s website at www.nevro.com, as well as an archived recording.

On August 8, 2019 Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), reported financial results for the second quarter ended June 30, 2019 and provided a summary of recent events (Press release, Regulus, AUG 8, 2019, View Source [SID1234538466]).

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"With the completed financing and restructuring of our term loan, we believe we are in a good position to work expeditiously to address the clear requirements outlined by FDA to reinitiate the MAD clinical study for RGLS4326," said Jay Hagan, CEO of Regulus. "We will also be evaluating potential options to initiate single dose studies in order to further characterize the molecule."

Second Quarter 2019 Corporate Highlights and Recent Updates

Private Financing: In May 2019, the Company closed the first tranche of its $41.8 million private placement of equity (the "Private Placement"). The Company received net proceeds of approximately $15.7 million from the first tranche, after deducting placement agent fees and other offering expenses. Subject to the Company’s public announcement on or before December 31, 2019 of its plan to recommence the Phase 1 multiple ascending dose ("MAD") clinical trial for RGLS4326 based upon correspondence from the United States Food and Drug Administration ("FDA"), the investors who purchased securities in the first tranche of the Private Placement have agreed to purchase shares of non-voting convertible preferred stock and accompanying warrants to purchase shares of common stock in a second closing (the "Milestone Closing"). If the Milestone Closing occurs, the gross proceeds to the Company from that closing will be approximately $25.1 million. The Company expects to use the proceeds from the Private Placement primarily to advance RGLS4326 for the treatment of autosomal dominant polycystic kidney disease ("ADPKD"), to advance select programs from its pipeline of microRNA therapies and for general corporate purposes. Excluding any potential proceeds from the Milestone Closing, the Company believes it has sufficient cash to fund operations into mid-2020.
Term Loan Amendments: In May 2019, and concurrently with the Private Placement, the Company amended its Term Loan with Oxford Finance to provide a new twelve-month period of interest-only payments, commencing May 2019, and a two-year extension of its maturity date from June 2020 to May 2022. Upon the closing of the second tranche of the Company’s Private Placement, the Company will receive an additional twelve-month period of interest-only payments, commencing May 2020.
RG-012 Transition to Sanofi: In November 2018, the Company and Sanofi agreed to transition further development activities of the miR-21 programs, including the Company’s RG-012 program, to Sanofi who will be responsible for all costs incurred in the development of these miR-21 programs (the "2018 Sanofi Amendment"). As of June 30, 2019, the transition activities, including the transfer of the investigational new drug application ("IND"), were complete. The Company received a total of $6.8 million in upfront and material transfer-related payments, which were recognized as revenue in the three months ended March 31, 2019. Regulus is also eligible to receive up to $40 million in clinical milestone payments.
Lease Agreement: In June 2019, the Company entered into an amendment of its lease (the "Lease Amendment") of 24,562 square feet located at 10628 Science Center Drive Suite 100, San Diego, California 92121. Under the terms of the Lease Amendment, the expiration of the lease was accelerated from June 30, 2023 to June 30, 2019, and the lease terminated on July 1, 2019. Concurrently with the Lease Amendment, the Company entered into a new lease agreement (the "New Lease") for 8,727 square feet located at 10628 Science Center Drive, Suite 225, San Diego, California, 92121, which it uses as its new principal offices and laboratory for research and development. This relocation reduced the Company’s facility size by approximately 65% and reduced its future contractual lease obligations by approximately 78%.
Management Transition: In July 2019, the Company appointed Cris Calsada as its new Chief Financial Officer, effective August 30, 2019. Ms. Calsada joins Regulus from Sanifit where she has served as Chief Financial Officer since December 2017. Ms. Calsada brings to Regulus’ senior management team a unique combination of financial, operational and managerial experience. She has over 20 years of leadership experience in the life sciences and technology industries. Prior to her employment with Sanifit, Ms. Calsada was self-employed as a finance consultant to various life sciences companies. From 2004 until its acquisition in 2015, she served in positions of increasing responsibility with Ambrx, most recently serving as its Chief Operating Officer and Vice President of Finance. Prior to Ambrx, she worked for Sony Online Entertainment as its Executive Director of Finance and Controller. Earlier in her career, she practiced as a certified public accountant. Ms. Calsada received a B.S. in Business Administration with emphasis in Accounting from San Diego State University and an M.B.A. from the University of Southern California Marshall School of Business. Ms. Calsada’s appointment follows the resignation of the Company’s previous Chief Financial Officer, Dan Chevallard, in July 2019.
Program Updates

RGLS4326 for ADPKD: In January 2019, the Company announced data from a planned interim analysis of a new mouse chronic toxicity study after 13 weeks of dosing in which no adverse or other significant findings across the range of doses tested were shown. In January 2019, the Company submitted a comprehensive data package for RGLS4326 to FDA that included the results from the planned 13-week interim analysis of the repeat mouse chronic toxicity study, as well as results from additional investigations, analytical testing, additional data from the previously terminated mouse chronic toxicity study, data from the completed Phase I single ascending dose ("SAD") study and data from the first cohort of the Phase I MAD study, to support its plan to resume the Phase I MAD study. After review of the requested submission, FDA notified the Company of additional nonclinical data requirements and placed the IND on a partial clinical hold, formalizing the specific requirements to initiate the MAD study and further proceed into chronic dosing in ADPKD patients. The additional data requirements have been outlined in two parts. In order to resume the MAD study, FDA has requested the final reports from the chronic toxicity studies in both mice and non-human primates and satisfactory related analyses to ensure subjects can be safely dosed. Additional data and analyses from new nonclinical studies, planned to be generated over the next several quarters, will be required for chronic dosing, and may also be used to support the resumption of the MAD study. Regulus is allowed to proceed with additional SAD clinical studies as part of the process to gather additional supporting information to guide the future development of the program.
Anti-miR-132 for Nonalcoholic Steatohepatitis (NASH): In April 2019, Regulus presented a late breaker poster at the EASL International Liver Congress describing the development of its lead anti-miR-132 for the treatment of NASH. Across multiple animal models of NASH, the lead candidate demonstrated improvement in key endpoints, including NAFLD Activity Score (NAS), liver transaminases, hyperglycemia, and disease-related gene expression. In the diet-induced NASH mouse model (Amylin model) after two to four weekly doses, early onset of improvement across multiple disease parameters including liver triglycerides and blood levels of transaminases was observed. After nine weeks of treatment, there was evidence of sustained benefit with significant improvement of liver fibrosis and hyperglycemia compared to control-treated animals. The Company believes that targeting dysregulated microRNA in a complex disease like NASH may offer a unique mechanism of action from other programs in development. The Company plans to seek a partner to further advance the development of this program.
Second Quarter 2019 Financial Results

Cash Position: As of June 30, 2019, Regulus had $19.6 million in cash and cash equivalents.

Revenue: Revenue was less than $0.1 million and $6.8 million for the three and six months ended June 30, 2019, respectively, compared to less than $0.1 million for each the three and six months ended June 30, 2018. The increase for the six months ended June 30, 2019 was attributable to revenue recognition of the upfront payments received under the 2018 Sanofi Amendment related to the transfer of RG-012.

Research and Development (R&D) Expenses: R&D expenses were $1.8 million and $7.8 million for the three and six months ended June 30, 2019, compared to $10.0 million and $21.8 million for the same periods in 2018. The decreases were driven by decreases in external development expenses, primarily attributable to the voluntary pause of the RGLS4326 Phase 1 MAD clinical study in the third quarter of 2018 and commencement of the transfer of the RG-012 program to Sanofi in the fourth quarter of 2018. Additionally, the decreases were driven by reductions in personnel and internal expenses, primarily attributable to a reduction in costs subsequent to our corporate restructuring in the third quarter of 2018.

General and Administrative (G&A) Expenses: G&A expenses were $2.9 million and $6.4 million for the three and six months ended June 30, 2019, compared to $3.3 million and $7.1 million for the same periods in 2018. These amounts reflect personnel-related and ongoing general business operating costs.

Net Loss: Net loss was $5.0 million, or $0.30 per share (basic and diluted), and $8.3 million, or $0.61 per share (basic and diluted), for the three and six months ended June 30, 2019, respectively, compared to $13.8 million, or $1.59 per share (basic and diluted), and $29.9 million, or $3.44 per share (basic and diluted), for the same periods in 2018. Historical and current period net loss per share values have been retroactively adjusted to reflect our October 2018 reverse stock split.

About Autosomal Dominant Polycystic Kidney Disease (ADPKD)

ADPKD, caused by the mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60.

About RGLS4326

RGLS4326 is a novel oligonucleotide designed to inhibit miR-17 and designed to preferentially target the kidney. Preclinical studies with RGLS4326 have demonstrated direct regulation of PKD1 and PKD2 in human ADPKD cyst cells, a reduction in kidney cyst formation, improved kidney weight/body weight ratio, decreased cyst cell proliferation, and preserved kidney function in mouse models of ADPKD.

On August 8, 2019 Synthetic Biologics, Inc. (NYSE American: SYN), a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, reported financial results for the three months ended June 30, 2019 (Press release, Synthetic Biologics, AUG 8, 2019, View Source [SID1234538465]). The Company also announced today a clinical trial agreement with Washington University School of Medicine in St. Louis ("Washington University") to conduct a Phase 1b/2a clinical trial of SYN-004 (ribaxamase), with enrollment expected to begin in the first quarter of 2020.

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"Our clinical trial collaboration with Washington University is an important step in our pursuit of a more cost-effective development strategy for SYN-004 targeting a more specialized patient population," stated Steven A. Shallcross, Chief Executive and Financial Officer. "SYN-004’s unique mechanism of action designed to degrade intravenous (IV) beta-lactam antibiotics and prevent dysbiosis of the gut microbiome has the potential to significantly improve outcomes for patients who undergo allogeneic hematopoietic cell transplantation (HCT), an area of significant unmet medical need."

"Prompt initiation of broad-spectrum IV beta-lactam antibiotics at onset of fever after conditioning chemotherapy for allogenic HCT is a life-saving intervention. However, this causes significant disruption of the microbiome, which places these patients at very high risk for infection due to some of our greatest antibiotic resistant threats, such as Clostridioides difficile, vancomycin-resistant Enterococci (VRE), and multidrug-resistant Gram-negative bacteria. We are seeking to determine if coadministration of SYN-004 while the patient is receiving IV beta-lactam antibiotics will preserve the microbiome and thus mitigate the risk from these threats," said Dr. Erik R. Dubberke Professor of Medicine and Clinical Director, Transplant Infectious Diseases at Washington University. "There are data to suggest preservation of the microbiome in allogeneic HCT recipients results in improved immune function after HCT as well. This would further enhance these patients’ outcomes and quality of life."

Mr. Shallcross continued, "During the second quarter, we remained focused on executing our strategy to advance our portfolio of gastrointestinal (GI) and microbiome-focused clinical programs. We held a highly informative pre-IND meeting with the U.S. Food and Drug Administration (FDA) for our SYN-020 intestinal alkaline phosphatase (IAP) program and clarified the parameters for IND-enabling toxicology studies. These activities are ongoing and will support our anticipated Investigational New Drug (IND) application which we intend to file promptly during the first quarter of 2020." Mr. Shallcross concluded, "Interest from prospective patients in our investigator-sponsored Phase 2b clinical trial of SYN-010 in breath-methane positive irritable bowel syndrome with constipation (IBS-C) patients remains strong. However, after consulting with the investigators at Cedars-Sinai Medical Center, the study sponsor, enrollment has been extended to accommodate higher than anticipated screen-fail rates. This is, in part, due to errant laxative use during the screening period that adversely impacts baseline measurements of IBS-C symptoms and breath-methane levels. Rigorous screening and reliable baseline parameters are critical to all IBS-C clinical trials in order to ensure the possibility of generating a meaningful data set of the highest quality. At this time, we are discussing with Cedars-Sinai the opportunity for a data read out in the first half of 2020, extending our previous guidance from the fourth quarter of 2019. We look forward to sharing important updates and progress for this and all our GI and microbiome-focused clinical programs."

Clinical Development and Operational Update

Entered into a Clinical Trial Agreement with Washington University School of Medicine in St. Louis to conduct a Phase 1b/2a clinical trial of SYN-004 (ribaxamase)
Under the terms of this agreement, Synthetic Biologics will serve as the sponsor of the study and supply SYN-004 (ribaxamase) and Dr. Dubberke will serve as the principal investigator along with his Washington University colleague Dr. Mark A. Schroeder, Associate Professor of Medicine, Division of Oncology, Bone Marrow Transplantation and Leukemia,
Enrollment is expected to begin during the first quarter of 2020, contingent upon review by the FDA and approval of the clinical study protocol by Washington University’s Institutional Review Board (IRB),
The proposed study is a Phase 1b/2a single-center, randomized, double-blinded, placebo-controlled clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of oral SYN-004 (ribaxamase) in up to 36 adult allogeneic HCT recipients,
Study participants will be enrolled into three sequential cohorts that will be administered a different study-assigned IV beta-lactam antibiotic. Eight participants in each cohort will receive SYN-004 (ribaxamase) and four will receive placebo,
Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee, which will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic,
The proposed study will also evaluate potential protective effects of SYN-004 (ribaxamase) on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 (ribaxamase) in allogeneic HCT recipients;
Enrollment is ongoing in the Phase 2b investigator-sponsored clinical study of SYN-010, for the treatment of IBS-C
The Phase 2b clinical study is being conducted by the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai Medical Center and is a 12-week, placebo-controlled, double-blind, randomized clinical trial evaluating two dose strengths of oral SYN-010 (21 mg and 42 mg) in approximately 150 patients diagnosed with IBS-C,
The primary objective for the study will be to determine the efficacy of SYN-010, measured as an improvement from baseline in the weekly average number of complete spontaneous bowel movements (CSBMs) during the 12-week treatment period for SYN-010 21 mg and 42 mg daily doses relative to placebo,
Secondary efficacy endpoints for both dose strengths of SYN-010 will measure changes from baseline in abdominal pain, bloating, stool frequency as well as the use of rescue medication relative to placebo,
A data readout is anticipated in 1H 2020,
Cedars-Sinai Medical Center and Synthetic Biologics are co-funding the study. The patent rights covering the use of SYN-010 are owned by Cedars-Sinai Medical Center and are exclusively licensed by Cedars-Sinai Medical Center to Synthetic Biologics;
Evaluated potential clinical development strategies to advance SYN-020 (intestinal alkaline phosphatase) to and through clinical trials targeting areas of significant unmet medical need, including enterocolitis associated with radiation therapy for cancer
Held Pre-IND meeting with FDA and clarified the requirements for IND-enabling toxicology studies
Exploratory study found SYN-020 enhanced 5-FU tumor treatment in a mouse ectopic colon cancer tumor model. A confirmatory study is ongoing with larger cohort sizes and additional mechanistic endpoints which, if repeated, may allow for further broadening of the clinical development strategy for this program,
Anticipate filing a US IND application in Q1 2020;
Continued to exercise prudent cash management and financial stewardship
Further reduced cash burn, extending projected cash runway to fund operations through at least the end of Q3 2020;
Quarter Ended June 30, 2019 Financial Results

General and administrative expenses decreased by 27% to $1.0 million for the three months ended June 30, 2019, from $1.4 million for the three months ended June 30, 2018. This decrease is primarily due to decreased stock-based compensation expense related to forfeitures and decreased options grants, along with the reduction of investor relations and consulting costs. The charge related to stock-based compensation expense was $59,000 for the three months ended June 30, 2019, compared to $264,000 the three months ended June 30, 2018.

Research and development expenses decreased by 27% to $2.6 million for the three months ended June 30, 2019, from $3.6 million for the three months ended June 30, 2018. This decrease is primarily the result of lower SYN-004 (ribaxamase) indirect program costs for the three months ended June 30, 2019, including salary and related expense reductions resulting from the 2018 restructuring and the fact that no clinical trial activity for SYN-004 (ribaxamase) was ongoing during the quarter, offset by an increase in manufacturing costs for SYN-020. The research and development costs incurred during the quarter were primarily related to the investigator-sponsored Phase 2b clinical study of SYN-010, a potential Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, and the continued development of SYN-020. Research and development expenses also include a charge relating to stock-based compensation expense of $31,000 for the three months ended June 30, 2019, compared to $293,000 for the three months ended June 30, 2018.

Other income was $80,000 for the three months ended June 30, 2019, compared to other income of $789,000 for the three months ended June 30, 2018. Other income for the three months ended June 30, 2019 is primarily comprised of interest income while the three months ended June 30, 2018 is comprised of non-cash income of $783,000 from the change in fair value of warrants. The decrease in the fair value of the warrants was due to the decrease in our stock price.

Cash and cash equivalents as of June 30, 2019 was $21.7 million, a decrease of $7.2 million from December 31, 2018.

Conference Call

Synthetic Biologics will hold a conference call today, Thursday, August 8, 2019, at 4:30 p.m. (ET). The dial-in information for the call is as follows, U.S. toll free: +1 888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.