On May 13, 2021 Applied DNA Sciences, Inc. (NASDAQ: APDN) (the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing, reported consolidated financial results for the three and six months ended March 31, 2021 (Press release, Applied DNA Sciences, MAY 13, 2021, View Source [SID1234579927]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to deliver a strong fiscal second quarter with year-over-year revenue growth of 384%, capping an impressive first half of the fiscal year distinguished by demand for our COVID-19 diagnostics and surveillance testing offerings (cumulatively "COVID-19 testing business")," said Dr. James A. Hayward, president and CEO, Applied DNA. "Our strategic and operational execution across non-COVID-19 testing initiatives was also notable: we launched our first-ever clinical trial for a therapeutic candidate in the form of a LinearDNA COVID-19 vaccine candidate for the veterinary market; advanced our cGMP capabilities and compliance roadmap that is a precursor to securing more lucrative CMO relationships and lays the foundation potentially to disrupt the market for the manufacturing of nucleic acid-based therapies; established a recurring revenue stream from the dietary supplements industry via Nutrition21’s use of our CertainT platform; strengthened our capital position, and deepened the management team to support our growth goals."

Continued Dr. Hayward, "Our COVID-19 testing strategy is increasingly informed by the acceleration in vaccine distribution. While traditional positive/negative testing remains a component of our go-to-market strategy, we believe that we are well-positioned despite increasing vaccination rates given our ability to detect SARS-COV-2 mutations. The expansion of our COVID-19 product portfolio with our Selective Genomic Surveillance (SGS) Panel and expanded intended use of our EUA for our LineaTM COVID-19 Assay Kit to include asymptomatic serial screening testing reflects a differentiated capability that expands our addressable market to include populations that can serve as a nexus for vaccinated and under-vaccinated populations coming together with increasing frequency, such as skilled nursing facilities, and supports the reopening of schools and workplaces. With our newly expanded intended use, together with the receipt of a New York clinical laboratory permit and CLIA certification for COVID-19 testing using EUA-authorized methods and devices by our Applied DNA Clinical Labs, LLC subsidiary, we believe our COVID-19 testing business presents a compelling opportunity for continued top-line growth.

"During the second half of the fiscal year, we will focus on positioning our COVID-19 testing business for the expected ongoing need for tests and services to support clients’ reopening strategies. While today our SGS Panel is available on a research use only (RUO) basis, our logical next step would be to seek an EUA to bring this critical tool out from the lab and to every Emergency Room and other healthcare providers that serve as the first line of defense against coronavirus variants to potentially inform their use of monoclonal antibody and convalescent plasma therapies. Concurrently and in line with our phased approach to cGMP that is further bolstered by preliminary positive neutralizing antibody results in domestic felines in our LinearDNA COVID-19 vaccine candidate clinical trial, we intend to explore an expansion of our LinearDNA-based therapeutic pipeline into classes of therapies that will best utilize the many benefits of our LinearDNA platform.

"While the speed and shape of the global recovery and timing of its impact on our supply chain security business remain uncertain, over the past year, we have seen brands and their supply chains put more emphasis on supply chain security and transparency to enhance their market position exiting the pandemic. We continue to position our CertainT platform as an enabler of the trust that both brands and consumers seek in a post-pandemic world, which, following the passage of the Uyghur Forced Labor Prevention Act, has further catalyzed our interest in leveraging our deep expertise in cotton genotyping and new next-generation sequencing capability to support brands’ regulatory requirements and ethical responsibilities."

Concluded Dr. Hayward, "Our strong balance sheet affords us substantial strategic and operational flexibility, as well as the ability to make both short- and longer-term investments in our businesses. We believe these investments in R&D and pre-commercial and commercial initiatives further enhance our growth profile."

Fiscal Second Quarter 2021 Financial Highlights:

Revenues increased 384% for the second quarter of fiscal 2021 to $2.7 million, compared with $552 thousand reported in the same period of the prior fiscal year and increased 65% from $1.6 million for the first quarter of fiscal 2021. The increase in revenues year over year was due primarily to an increase in service revenues of approximately $1.4 million and an increase of $767 thousand in product revenues. The increase in service revenue was primarily from revenues derived from our safeCircle COVID-19 surveillance testing. The increase in product revenue was mainly attributable to an increase in sales of our Linea COVID-19 Assay Kit.
Total operating expenses increased to $4.6 million for the second fiscal quarter of 2021, compared with $3.0 million in the prior fiscal year’s second quarter. This increase is primarily attributable to an increase in payroll of $315 thousand for staffing of Applied DNA Clinical Labs, LLC (ADCL), as well as an increase of $277 thousand for supplies and equipment to operate the ADCL laboratory. The increase in operating expenses also related to an increase in stock-based compensation expense of $422 thousand relating to officer stock option grants that vested immediately. The increase is also the result of increases in research and development expenses of $171 thousand and depreciation and amortization of $133 thousand.
Net loss applicable to common stockholders for the quarter ended March 31, 2021 was $1.5 million, or $0.21 per share, compared with a net loss of $3.0 million, or $0.79 per share, for the quarter ended March 31, 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $1.5 million and negative $2.6 million for the quarters ended March 31, 2021 and 2020, respectively. See below for information regarding non-GAAP measures.
Cash and cash equivalents stood at $13.9 million on March 31, 2021, compared to $7.8 million as of September 30, 2020.
Six-Month Financial Highlights:

Revenues increased 262% for the first six months of fiscal 2021 to $4.3 million, compared with $1.2 million reported in the same period of the prior fiscal year. The increase in revenues year over year was due primarily to an increase in service revenues of approximately $2.0 million and an increase of $1.1 million in product revenues. The increase in service revenue was primarily from revenues derived from our safeCircle COVID-19 surveillance testing. The increase in product revenue was mainly attributable to an increase in sales of our Linea Assay Kit.
Total operating expenses increased to $9.0 million for the first six months of fiscal 2021, compared with $6.1 million in the same period of the prior fiscal year. This increase is primarily attributable to an increase in payroll of $1 million. The increase in payroll relates to additional headcount to staff at ADCL, as well as an increase for officer bonuses. The increase in operating expenses also related to an increase in stock-based compensation expense of $725 thousand primarily relating to officer stock option grants that vested immediately.
Net loss applicable to common stockholders for the six-months ended March 31, 2021 was $6.3 million, or $1.00 per share, compared with a net loss of $5.6 million, or $1.76 per share, for the first six months of fiscal 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $3.9 million for the first six months of fiscal 2021, compared to negative $5.0 million for the same period in the prior fiscal year. See below for information regarding non-GAAP measures.
Fiscal Second Quarter 2021 Conference Call Information

The Company will hold a conference call and webcast to discuss its fiscal second quarter-end 2021 results on Thursday, May 13, 2021 at 4:30 PM ET. To participate on the conference call, please follow the instructions below. While every attempt will be made to answer investors’ questions on the Q&A portion of the call, not all questions may be answered.

Webcast replay: View Source
For those unable to attend the live call, a copy of management’s PowerPoint presentation will be available for review under the ‘IR Calendar’ section of the company’s Investor Relations web site: View Source

Information about Non-GAAP Financial Measures

As used herein, "GAAP" refers to accounting principles generally accepted in the United States of America. To supplement our condensed consolidated financial statements prepared and presented in accordance with GAAP, this earnings release includes Adjusted EBITDA, which is a non-GAAP financial measure as defined in Rule 101 of Regulation G promulgated by the Securities and Exchange Commission. Generally, a non-GAAP financial measure is a numerical measure of a company’s historical or future performance, financial position, or cash flows that either excludes or includes amounts that are not normally excluded or included in the most directly comparable measure calculated and presented in accordance with GAAP. The presentation of this non-GAAP financial information is not intended to be considered in isolation or as a substitute for, or superior to, the financial information presented in accordance with GAAP. We use this non-GAAP financial measure for internal financial and operational decision-making purposes and as a means to evaluate period-to-period comparisons of the performance and results of operations of our core business. Our management believes that these non-GAAP financial measures provide meaningful supplemental information regarding the performance of our business by excluding non-cash expenses that may not be indicative of our recurring operating results. We believe this non-GAAP financial measure is useful to investors as they allow for greater transparency with respect to key metrics used by management in its financial and operational decision making.

"EBITDA"- is defined as earnings (loss) before interest expense, income tax expense and depreciation and amortization expense.

"Adjusted EBITDA"- is defined as EBITDA adjusted to exclude (i) stock-based compensation and (ii) other non-cash expenses.

On May 13, 2021 HTG Molecular Diagnostics, Inc. (Nasdaq: HTGM) (HTG), a life science company whose mission is to advance precision medicine, reported its financial results for the first quarter ended March 31, 2021 (Press release, HTG Molecular Diagnostics, MAY 13, 2021, View Source [SID1234579926]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Recent Business Highlights

● Released a second technical white paper (White Paper Two) characterizing the company’s planned transcriptome panel using the HTG EdgeSeq technology. White Paper Two, among other things, compares the performance and feasibility of a prototype of HTG’s planned transcriptome panel to RNA sequencing (RNA-Seq) across multiple cancer indications. White Paper Two also demonstrates the feasibility and expected performance of the transcriptome panel, including:

○ Ability to differentiate samples based on gene expression profiles;
○ Repeatability amongst replicates from multiple cancer indications with archived samples;
○ Accuracy of differential expression analysis using a direct comparison to RNA-Seq;
○ Potential as a robust alternative to RNA-Seq for gene expression profiling while maintaining the advantages of the HTG EdgeSeq technology.

With the feasibility testing for all elements of the panel’s design complete, the company is now in the optimization phase of development, working to further improve the panel’s design, workflow, and robustness. Having completed our final round of probe quality control testing, defined our quality control metric strategy and finalized the reagent formulation during the quarter, we have ordered our final probe pool for the panel. Final panel design lock is anticipated in the second quarter of 2021 followed by formal panel design verification with initial commercialization anticipated by the third quarter of 2021.

● Increased participation in the company’s transcriptome panel Early Adopter Program (EAP), refining study details with over 25 collaborators to date, including those in both academia and pharma. The EAP allows a select group of customers access to the initial transcriptome panel for use in their laboratories or through services performed by HTG prior to commercial launch of the panel.

"Our team continues to be very optimistic about the launch of the transcriptome panel using our HTG EdgeSeq technology," said John Lubniewski, President and CEO of HTG. "Data published in our second white paper highlight the potential of this panel as a robust, clinically deployable alternative to RNA-Seq for gene expression profiling. We believe the benefits of our HTG EdgeSeq technology and the transcriptome panel, including ease of use, cost savings, turnaround time and broad applicability, will make this a very attractive alternative for gene expression profiling applications. We continue to meet our development milestones and look forward to providing updates on our progress in the coming months."

"In the fourth quarter of 2020, our base business showed signs of recovery after experiencing a substantial impact from COVID-19 in the second and third quarters of 2020. The reopening process stalled again in the first quarter of 2021 in Europe and our pharmaceutical company customers have continued a slow return to pre-COVID-19 clinical trial levels. We are hopeful of a return to pre-COVID revenue levels as vaccinations become more widely available and business continues to normalize," Mr. Lubniewski continued.

First Quarter 2021 Financial Highlights:

Total revenue for the first quarter ended March 31, 2021 was $1.4 million, compared with $2.2 million for the same period in 2020. HTG believes the decrease in revenue is a result of the impact of the COVID-19 pandemic requiring the closure of customer facilities, causing a significant reduction in oncology-related clinical trial activity or limiting the ability of our customers to operate at pre-pandemic levels.

Product and product-related services revenue was $1.4 million, compared with $2.0 million for the same period in 2020. Throughout the pandemic, HTG’s ability to ship instruments and consumables to customer facilities and the ability of its customers to prepare and ship samples to HTG’s VERI/O laboratory for processing has been limited.

There was no collaborative development services revenue for the quarter ended March 31, 2021, compared with $0.2 million for the same period in 2020, reflecting the completion of remaining tasks under existing arrangements. The company has ongoing sales efforts to identify and contract new programs in this area.

Net loss from operations for the first quarter ended March 31, 2021 was $4.6 million, compared with $5.4 million for the same period in 2020. Net loss per share was $(0.80) for the quarter ended March 31, 2021 compared with $(1.27) for the same period in 2020.

Cash, cash equivalents and short-term available-for-sale securities totaled $30.8 million as of March 31, 2021, with current liabilities of approximately $8.3 million and non-current liabilities of $11.5 million.

Conference Call and Webcast:

HTG will host a conference call for the investment community today beginning at 4:30 p.m. Eastern Time. Conference call and webcast details are as follows:

On May 13, 2021 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported financial results for the first quarter ended March 31, 2021 (Press release, Alpine Immune Sciences, MAY 13, 2021, View Source [SID1234579925]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The first quarter of this year has been highly productive as we continue to make strong progress across our pipeline. We look forward to sharing the first clinical data update on NEON-1, a Phase 1 dose escalation and expansion study of ALPN-202 monotherapy, at the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "In addition, we continue our focus on the imminent global Phase 2 study of ALPN-101 in systemic lupus erythematosus, targeted to initiate around the middle of the year."

First Quarter 2021 and Recent Updates

ALPN-202: Conditional CD28 costimulator and dual checkpoint inhibitor
In April 2021, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, Dr. Mark Voskoboynik from Nucleus Network and The Alfred Hospital in Melbourne, Australia, presented a Trials in Progress poster describing the ongoing first-in-human, Phase 1 clinical trial involving monotherapy with ALPN-202, the company’s lead oncology program.
In April 2021, Alpine announced an upcoming clinical data presentation on NEON-1 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting scheduled to take place June 4, 2021.
Research
In April 2021, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, Alpine researchers demonstrated the use of directed evolution to engineer novel variant immunoglobulin domain (vIgD) Fc fusion proteins that enable tumor antigen-dependent CD28 costimulation.
General Corporate
Promotion of Remy Durand, Ph.D. to Chief Business Officer: Dr. Durand joined Alpine Immune Sciences in 2018 as Vice President, Business Development and Corporate Strategy, and has played a leading role in building the company’s partnerships with AbbVie and Adaptimmune, and has represented the company at investor meetings and conferences.
Appointed Pamela Holland, Ph.D. as Senior Vice President, Research: Dr. Holland is an experienced cancer biologist with a proven track record of successfully discovering and progressing multiple preclinical therapeutics into clinical development, most recently at Surface Oncology and Amgen.
First Quarter 2021 Financial Results

As of March 31, 2021, we had cash, cash equivalents, restricted cash, and investments totaling $115.4 million. Net cash used in operating activities for the quarter ended March 31, 2021 was $16.0 million compared to net cash used in operating activities of $9.7 million for the quarter ended March 31, 2020. We recorded net losses of $10.6 million and $5.5 million for the quarters ended March 31, 2021 and 2020, respectively.

Collaboration revenue for the quarter ended March 31, 2021 was $3.2 million and related to our agreement with AbbVie, compared to $1.1 million related to our agreement with Adaptimmune for the quarter ended March 31, 2020.

Research and development expenses for the quarter ended March 31, 2021 were $10.4 million compared to $4.9 million for the quarter ended March 31, 2020. The increase was primarily attributable to increases in contract manufacturing and process development of our product candidates, clinical trial activities, and personnel-related expenses.

General and administrative expenses for the quarter ended March 31, 2021 were $3.3 million compared to $1.8 million for the quarter ended March 31, 2020. The increase was primarily attributable to increases in professional and legal services, personnel-related expenses, and insurance and facility costs to support the growth and expansion of our business.

Alpine expects that its current cash resources, combined with the potential $75 million in pre-option exercise milestones payable under its option and license agreement with AbbVie, for the development and commercialization of ALPN-101, are sufficient to fund Alpine’s planned operations through 2023.

On May 13, 2021 Achieve Life Sciences, Inc. (NASDAQ:ACHV), a clinical-stage pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation and nicotine addiction, reported first quarter 2021 financial results and provided an update on the cytisinicline clinical development program (Press release, OncoGenex Pharmaceuticals, MAY 13, 2021, View Source [SID1234579924]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Recent Events & Highlights

Provided update on the Phase 3 ORCA-2 clinical trial evaluating the efficacy and safety of 3.0 mg cytisinicline dosed 3 times daily compared to placebo in 750 adult smokers at 17 clinical sites in the United States
Published Phase 2b ORCA-1 safety, efficacy, and compliance results in Nicotine and Tobacco Research
Announced the appointment of Dr. Bridget Martell and Dr. Cindy Jacobs to Achieve’s Board of Directors
Published RAUORA Head-to-Head Non-Inferiority Clinical Trial Comparing Cytisinicline and Chantix (varenicline) in Addiction
"In the first quarter, we’ve seen great interest and increased momentum in the ORCA-2 trial and look forward to completing enrollment by the middle of the year," commented John Bencich, Chief Executive Officer of Achieve. "We will continue to focus our efforts on execution of the Phase 3, ensuring all required NDA-enabling activities remain on track, and furthering our discussions with potential strategic partners to prepare for cytisinicline commercialization."

Phase 3 ORCA-2 Trial
The Phase 3 ORCA-2 trial continues to enroll at 17 clinical sites in the United States. Approximately 750 adult smokers will be randomized to one of three study arms to determine the efficacy and safety of cytisinicline administered for either six or twelve weeks, compared to placebo. The primary endpoint is biochemically verified continuous abstinence during the last four weeks of treatment in the six and twelve-week cytisinicline treatment arms compared to placebo. Each treatment arm will be compared independently to the placebo arm and the trial will be determined to be successful if either or both of the cytisinicline treatment arms show a statistical benefit compared to placebo. The trial is expected to complete enrollment by the middle of 2021.

ORCA-1 Results Published in Nicotine and Tobacco Research
Results from the Phase 2b ORCA-1 trial were published in the scientific journal Nicotine and Tobacco Research. ORCA-1 evaluated the efficacy and safety of cytisinicline across various dosing and administration schedules in 254 smokers in the United States. The publication reported that subjects treated with cytisinicline, regardless of dose or schedule, had statistically significantly higher (p<0.001) end of treatment abstinence rates compared to those treated with placebo. Participants in the 3.0 mg cytisinicline 3 times daily (TID) arm, were five times more likely to quit smoking than those in the placebo arm (OR of 5.04, 95% CI: 1.42, 22.32, p<0.001). Cytisinicline was well-tolerated with no serious or severe adverse events (AEs) reported.

Appointment of Drs. Martell and Jacobs to Board of Directors
Achieve announced the appointment of two new members to Achieve’s Board of Directors, Dr. Bridget Martell and Dr. Cindy Jacobs. Dr. Martell is board certified in both Internal and Addiction Medicine and is an experienced executive leader in the pharmaceutical industry. Dr. Jacobs serves as Achieve’s President and Chief Medical Officer, and in addition to her Board of Directors duties, will continue in her current role leading Achieve’s regulatory and clinical development efforts for cytisinicline.

RAUORA Trial Results Published in Addiction
Results from the Phase 3 RAUORA trial were published in the scientific journal Addiction. RAUORA evaluated the effectiveness and safety of cytisinicline compared to Chantix (varenicline) as a smoking cessation aid in 679 indigenous New Zealanders (Māori). The published results indicate that cytisinicline met the pre-specified non-inferiority endpoint, and was trending towards superiority with an Absolute Risk Difference of +4.29 in favor of cytisinicline (95% CI -0.22 to 8.79), and a 55% improvement in quit rates at six months in favor of cytisinicline when compared to Chantix. A Bayesian analysis of the primary efficacy outcome is ongoing. Additionally, statistically significant fewer overall AEs were reported in cytisinicline-treated subjects (Relative Risk 0.56, 95% CI 0.49 to 0.65, p<0.001) including a significantly lower rate of nausea when compared to subjects on Chantix.

Financial Results
As of March 31, 2021, the company’s cash, cash equivalents, and restricted cash was $29.7 million. Total operating expenses for the three months ended March 31, 2021 was $8.0 million. Total net loss for the three months ended March 31, 2021 was $8.0 million.

As of May 13, 2021, Achieve had 6,164,360 shares outstanding.

Conference Call Details
Achieve will host a conference call at 4:30 pm Eastern time today, Thursday, May 13, 2021. To access the webcast, log on to the investor relations page of the Achieve website at View Source Alternatively, access to the live conference call is available by dialing (877) 472-9809 (U.S. & Canada) or (629) 228-0791 (International) and referencing conference ID 6096445. A webcast replay will be available approximately two hours after the call and will be archived on the website for 90 days.

On May 13, 2021 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 first quarter ended March 31, 2021 and provided a corporate update (Press release, Regulus, MAY 13, 2021, View Source [SID1234579923]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited about the data we recently announced from the first cohort of our phase 1b clinical trial of RGLS4326 for the treatment of patients with ADPKD where we saw mean increases of greater than 50% and 20% in Polycystin 1 (PC1) and Polycystin 2 (PC2), respectively. PC1 and PC2 are the products of the PKD1 and PKD2 genes, and are depressed in patients with this disease. The trends for both suggest that with continued therapy, higher levels of these proteins may be attainable and less frequent dosing required. Additionally, RGLS4326 was well tolerated by all nine patients with no serious adverse events reported", stated Jay Hagan, CEO of Regulus. "Data from the first cohort provides the safety and pharmacokinetic data needed to complete the modeled safety margins. We plan to submit these data to FDA this summer in the context of our discussions regarding the remaining partial clinical hold requirements."

Program Updates

RGLS4326 for ADPKD: In February 2021, the Company completed enrollment in the first cohort of a Phase 1b clinical study for RGLS4326 in patients with ADPKD (The "Phase 1b"). The Phase 1b is an adaptive design, open-label, multiple dose study in up to three cohorts of patients with ADPKD. The study is designed to evaluate the safety, pharmacokinetics, and changes in levels of PC1 and PC2 in patients with ADPKD administered RGLS4326 every other week for a total of four doses. The dose level for the first cohort is 1 mg/kg of RGLS4326 and the dose level for the second cohort is 0.3 mg/kg. The third and final cohort will be dosed at a level to be determined based on the results of the first two cohorts. In May 2021, the Company announced top-line results from the first cohort of patients with ADPKD in its ongoing Phase 1b clinical trial of RGLS4326.

In the first cohort, nine patients were enrolled and received 1 mg/kg of RGLS4326 subcutaneously every other week for four doses. Safety, pharmacokinetics, and certain disease related biomarkers were evaluated through the course of the study. The biomarkers included: PC1 and PC2, kidney injury marker 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), as well as urea and creatinine and were chosen to evaluate changes in disease related measures.

Measured levels of PC1 and PC2 increased greater than 50% and 20%, respectively by the end of study compared to baseline levels. Regulus believes these initial data demonstrate that RGLS4326 engages the target miR-17 leading to increased expression of the PKD1 and PKD2 genes and the resultant increases in measured polycystin levels. Measured levels of PC1 and PC2 have been shown to inversely correlate with disease severity and are believed to be directly linked to the underlying genetic drivers of the disease. The overall trend in polycystin showed increasing levels of both PC1 and PC2 over time with a sustained effect suggesting less frequent dosing could be utilized. Importantly, at the time of the analysis, patient mutational status was not known and may further contribute to understanding differences in response rates. Approximately 85% of patients with ADPKD are reported to have a mutation in the PKD1 gene, while the remaining 15% have a mutation in the PKD2 gene. Additionally, the PKD1 gene has one predicted binding site for miR-17 while the PKD2 gene has two predicted binding sites for miR-17, potentially contributing to different response rates between the biomarkers.

RGLS4326 was well tolerated by all nine patients with no serious adverse events reported. All reported adverse events were mild and generally transient in nature.

Overall, the pharmacokinetic profile of RGLS4326 in patients with ADPKD was similar to that observed in a prior healthy volunteer study. Concentrations of RGLS4326 in plasma were greater in patients (Cmax ~ 3 ug/mL) relative to healthy volunteers (Cmax ~ 2 ug/mL), suggesting a lower dose in patients could achieve the desired exposure in the kidney, the target organ of interest.

Data from this first cohort is planned to be submitted for presentation at PKD Connect in June 2021 and at Kidney Week, the American Society of Nephrology annual meeting being held in November 2021.

Corporate Highlights

Lease Agreement for New Corporate Headquarters Executed and Relocation Completed: In February 2021, we entered into a lease agreement (the "New Lease") for 13,438 square feet located at 4224 Campus Point Court, Suite 210, San Diego, California, 92121, which is to be used as our new principal offices and laboratory for research and development. The move into the space leased under the New Lease was completed in April 2021. Concurrently with the New Lease, we assigned the lease to the space that had served as our previous corporate headquarters, and have no remaining obligations associated with the previous corporate headquarters lease after April 2021.

Financial Results

Cash Position: As of March 31, 2021, Regulus had $31.6 million in cash and cash equivalents.

Research and Development (R&D) Expenses: Research and development expenses were $3.3 million for the three months ended March 31, 2021, compared to $3.1 million for the same period in 2020. These amounts reflect internal and external costs associated with advancing our clinical and preclinical pipeline.

General and Administrative (G&A) Expenses: General and administrative expenses were $2.5 million for the three months ended March 31, 2021, compared to $2.4 million for the same period in 2020. These amounts reflect personnel-related and ongoing general business operating costs.

Net Loss: Net loss was $6.0 million, or $0.08 per share (basic and diluted), for the three months ended March 31, 2021, compared to $5.9 million, or $0.25 per share (basic and diluted), for the same period in 2020.

About 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 preferentially target the kidney. Preclinical studies with RGLS4326 have demonstrated direct regulation of Pkd1 and Pkd2, reduction of cyst growth in human in vitro ADPKD models, and attenuation of cyst proliferation and improvement of kidney function in mouse models of ADPKD. The RGLS4326 IND is currently on a partial clinical hold for treatment of extended duration by FDA until the second set of requirements outlined by the agency have been satisfactorily addressed. The Company will use information from the Phase 1 clinical studies, including the first cohort of the Phase 1b together with information from the recently completed additional nonclinical studies generated in 2020, in its plan to address the second set of requirements outlined in the Partial Clinical Hold letter to support studies of extended duration. Regulus plans to discuss its approach to addressing the remaining Partial Clinical Hold requirements with FDA in mid-2021. RGLS4326 received orphan drug designation from FDA in July 2020.