On August 6, 2019 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases, reported its financial results for the second quarter ended June 30, 2019 and provided an update on the company’s recent achievements and anticipated upcoming milestones (Press release, Audentes Therapeutics, AUG 6, 2019, View Source [SID1234538233]).

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"It is a very busy time at Audentes, and we are excited by the significant progress we have made across our portfolio," stated Matthew R. Patterson, Chairman and Chief Executive Officer. "Following collaborative interactions with FDA and EMA, we have initiated enrollment of eight additional XLMTM patients into an ASPIRO pivotal expansion cohort, which is designed to confirm the safety and efficacy profile of AT132 at a dose of 3×1014 vg/kg. We are optimistic that these data will support the submission of a BLA for AT132 in mid-2020."

Mr. Patterson continued, "We remain on track for a third quarter IND submission of AT845 for the treatment of Pompe disease. And importantly, we’ve made substantial progress advancing our DMD program. We expect patient dosing with NCH’s AT702 construct to commence as planned in the fourth quarter of 2019 and to submit an IND in the first quarter of 2020 for the Audentes AT702 construct, which is designed to serve as the platform for our rapid expansion into additional DMD genotypes next year. Together with our work in myotonic dystrophy, we believe this rich development pipeline positions us well for continued growth and industry leadership in the field of AAV-based genetic medicines for neuromuscular disease."

Recent Achievements & Upcoming Key Events

AT132 for XLMTM:

Positive data update from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of XLMTM, presented at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in May 2019.
3×1014 vg/kg selected as optimal dose.
Following collaborative interactions with the FDA and EMA, initiated enrollment of eight additional XLMTM patients into the ASPIRO pivotal expansion cohort, designed to confirm the safety and efficacy profile of AT132 at a dose of 3×1014 vg/kg.
Enrollment in the pivotal expansion cohort is expected to be complete in the fall of 2019.
BLA submission for AT132 planned in mid-2020; MAA submission planned for the second half of 2020.
Next clinical data presentation planned at the 24th International Annual Congress of the World Muscle Society (WMS) in Copenhagen, Denmark, October 1-5, 2019.
Additional information on the ASPIRO Pivotal Expansion Cohort:

The pivotal expansion cohort is enrolling eight patients, consisting of four age-matched pairs (+/- 6 months), with one patient from each pair randomized to receive a single dose of AT132 (3×1014 vg/kg) or serve as a delayed treatment control. Delayed treatment control patients will be administered AT132 following the collection of 24-week data from the full pivotal cohort.
Patients will be followed for safety and efficacy for five years, with the primary analysis occurring 24 weeks post treatment.
Key inclusion criteria: less than 5 years of age or have been enrolled in INCEPTUS, on invasive ventilator support for 20-24 hours per day, unable to sit without assistance for at least 30 seconds.
The primary efficacy endpoint is defined as change from baseline in INCEPTUS, on invasive ventilator support for 20-24 hours per day, unable to sit without assistance for at least 30 seconds.
The primary efficacy endpoint is defined as change from baseline in hours of ventilatory support over time through week 24. As of the April 2019 ASPIRO data analysis, all nine patients treated achieved sustained and meaningful reductions in ventilatory support, with four patients successfully completely weaned off of mechanical ventilation.
AT845 for Pompe Disease:

Completed IND-enabling dose ranging and toxicology studies.
On track to submit IND in the third quarter of 2019.
AT702/AT751/AT753 for DMD:

Plan to commence patient dosing in the fourth quarter of 2019 with AT702 produced by NCH. AT702 is designed to induce exon 2 skipping to treat DMD caused by duplications of exon 2 (Dup2) and mutations in exons 1-5 of the dystrophin gene.
Dose ranging and toxicology studies underway to support a first quarter 2020 IND submission for the Audentes AT702 construct and transition the balance of the AT702 DMD program into a Phase 1/2 clinical study utilizing this product candidate.
The construct backbone of the Audentes AT702 product is designed to serve as a vectorized exon skipping platform for rapid expansion into additional DMD genotypes.
Preclinical work is underway to advance AT751 and AT753 to treat DMD patients with genotypes amenable to exons 51 and 53 skipping.
In combination, AT702, AT751 and AT753 have the potential to address more than 25% of DMD patients; plan to leverage our vectorized exon skipping platform to develop additional product candidates with the potential to address up to 80% of DMD patients over time.
AT466 for DM1:

Preclinical vector screening studies underway.
Plan to submit IND in 2020.
Manufacturing:

Advanced chemistry, manufacturing, and controls (CMC) BLA and MAA-readiness efforts for AT132.
State-of-the-art, internal, large-scale cGMP manufacturing facility provides sufficient capacity for AT132 global commercialization as well as the near-term clinical development of all pipeline programs.
Completed construction and commissioning of state-of-the-art, internal plasmid manufacturing facility to support production of nonclinical and cGMP-grade plasmids for all of our development programs, including the potential commercialization of AT132.
Corporate:

Appointed Edward R. Conner, M.D. as Senior Vice President and Chief Medical Officer. Ed is responsible for leading the company’s global clinical development strategy and oversees clinical development, clinical operations, regulatory affairs, medical affairs and patient advocacy.
Promoted Fulvio Mavilio, Ph.D. to Senior Vice President of Translational Science. Fulvio is responsible for advancing the company’s pipeline from discovery through to IND-enabling preclinical development and oversees discovery biology, pharmacology/toxicology, bioinformatics and bioanalytics.
Second Quarter 2019 Financial Results

Cash Position: As of June 30, 2019, cash, cash equivalents and marketable securities were $378.6 million.
Research and Development Expenses: Research and development expense was $37.3 million for the second quarter of 2019 compared to $26.3 million for the same period in 2018, an increase of $11.0 million. The increase was primarily attributable to higher direct program expenses for AT132 and AT845, along with additional R&D headcount to advance clinical and pre-clinical programs. Included in R&D expense for the three months ended June 30, 2019 was $3.2 million of non-cash stock-based compensation expense, compared to $2.3 million in the same period in 2018. For the six months ended June 30, 2019, research and development expense was $77.1 million compared to $46.2 million for the same period in 2018.
General and Administrative Expenses: General and administrative expense was $9.8 million for the second quarter of 2019 compared to $6.3 million for the same period in 2018. The increase was primarily attributable to headcount increases and infrastructure investment to support growth. Included in G&A expense for the three months ended June 30, 2019 was $2.9 million of non-cash stock-based compensation expense, compared to $1.8 million in the same period in 2018. For the six months ended June 30, 2019, general and administrative expense was $21.8 million compared to $12.8 million for the same period in 2018.
Net Loss: Net loss was $44.8 million for the second quarter of 2019 compared to $31.4 million for the same period in 2018. Basic and diluted net loss per share for the three months ended June 30, 2019, was $1.01 compared with $0.85 for the same period in 2018. For the six months ended June 30, 2019, net loss was $94.2 million compared to $56.9 million for the same period in 2018. Basic and diluted net loss per share for the six months ended June 30, 2019, was $2.14 compared with $1.59 for the same period in 2018.
Conference Call
At 4:30 p.m. Eastern Time today, Audentes management will host a conference call and a simultaneous webcast to discuss its second quarter 2019 financial results and provide a corporate update. To access a live webcast of the conference call, please visit the Events & Presentations page within the Investors + Media section of the Audentes website at www.audentestx.com. Alternatively, please call (833) 659-8620 (U.S.) or (409) 767-9247 (international) and dial the conference ID# 4244738 to access the call.

A replay of the webcast will be available on the Audentes website for approximately 30 days.

On August 6, 2019 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that CEO Sandy Macrae will present at the 2019 Wedbush PacGrow Healthcare Conference in New York City (Press release, Sangamo Therapeutics, AUG 6, 2019, View Source [SID1234538318]). The presentation is scheduled for Wednesday, August 14 at 1:20 p.m. Eastern Time.

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The Wedbush presentation will be webcast live and may be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. The presentation will also be available on the Sangamo website after the event.

Earlier in the week, Dr. Macrae will participate in the BTIG Biotechnology Conference 2019 in a panel discussion, "Exploring the Novel Approaches to Treating Sickle Cell Disease". This event is scheduled for Monday, August 12 at 1:00 p.m. Eastern Time. No webcast is available for the BTIG event.

On August 6, 2019 Cambrex Corporation (NYSE: CBM), the leading small molecule company providing drug substance, drug product and analytical services across the entire drug lifecycle, reported that second quarter 2019 financial results will be released on Friday, August 9, 2019 before the market opens (Press release, Cambrex, AUG 6, 2019, View Source [SID1234538184]).

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The Company will host a conference call to discuss the financial results.

Second Quarter 2019 Earnings Conference Call

When: Friday, August 9, 2019 at 8:30 a.m. Eastern Time

Dial-in: 1-888-220-8451 for U.S.
1-323-794-2588 for International
Passcode: 9175707

Dial-in Replay: 1-888-203-1112 for U.S.
1-719-457-0820 for International
Passcode: 9175707
Available through Friday, August 16, 2019

Webcast: www.cambrex.com

On August 6, 2019 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the second quarter of 2019 and provided a business update (Press release, Regeneron, AUG 6, 2019, View Source [SID1234538202]).

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"We had a great quarter marked by top- and bottom-line growth as well as important advances across our innovative R&D engine," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We are further unlocking EYLEA’s potential to help patients with the recent approval in diabetic retinopathy, and are advancing a high-dose formulation into the clinic later this year. Dupixent is growing rapidly in moderate-to-severe atopic dermatitis and asthma, and we continue to receive new indications in younger patients and additional Type 2 diseases, including the recent U.S. approval for chronic rhinosinusitis with nasal polyposis. Lastly, our immuno-oncology platform, which includes Libtayo and our portfolio of bispecific antibodies, is progressing well, with the most advanced bispecific program, REGN1979 (CD20xCD3), entering a potentially pivotal Phase 2 trial in follicular lymphoma."

Key Pipeline Progress
Regeneron has 21 product candidates in clinical development, including five of the Company’s U.S. Food and Drug Administration (FDA) approved products for which it is investigating additional indications. Updates from the clinical pipeline include:
EYLEA (aflibercept) Injection

In May 2019, the FDA approved EYLEA for the treatment of diabetic retinopathy.

The supplemental Biologics License Application (sBLA) for EYLEA in a pre-filled syringe has a target action date of August 12, 2019.

Dupixent (dupilumab)

In May 2019, the European Commission (EC) approved Dupixent for use in adults and adolescents 12 years and older as an add-on maintenance treatment for severe asthma.

In June 2019, the FDA approved Dupixent for use with other medicines to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled.

The European Commission approved Dupixent, extending its approval in the European Union (EU) to include adolescents 12 to 17 years of age with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.

In August 2019, the Company and Sanofi announced that the Phase 3 trial to treat severe atopic dermatitis in children 6 to 11 years of age met its primary and secondary endpoints.

Libtayo (cemiplimab)

In June 2019, the EC granted conditional marketing authorization for Libtayo for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

A Phase 3 adjuvant study in CSCC was initiated.

REGN1979, a bispecific antibody against CD20 and CD3

In June 2019, the Company presented updated positive results from a study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma at the European Hematology Association (EHA) (Free EHA Whitepaper) meeting.

A Phase 2 study in relapsed or refractory follicular lymphoma (FL) is recruiting patients.

Praluent (alirocumab)

In April 2019, based upon data from the Phase 3 ODYSSEY OUTCOMES trial, the FDA approved a new indication for Praluent to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. The label was also updated to include data showing that treatment with Praluent was associated with a reduction in death from any cause.

REGN3500, an antibody to IL-33

In June 2019, the Company and Sanofi announced that the Phase 2 study in asthma met the primary endpoint of improvement in loss of asthma control when comparing REGN3500 monotherapy to placebo. In the trial, the greatest improvement was observed in patients with blood eosinophil levels ≥300 cells/microliter. Patients treated with Dupixent monotherapy did numerically better than REGN3500 across all endpoints. The combination of REGN3500 and Dupixent did not demonstrate increased benefit compared to Dupixent monotherapy in this trial.

Second Quarter 2019 Financial Results

Total Revenues: Total revenues increased by 20% to $1.934 billion in the second quarter of 2019, compared to $1.608 billion in the second quarter of 2018.

Net product sales were $1.205 billion in the second quarter of 2019, compared to $996 million in the second quarter of 2018. EYLEA net product sales in the United States were $1.160 billion in the second quarter of 2019, compared to $992 million in the second quarter of 2018. Overall distributor inventory levels for EYLEA in the United States remained within the Company’s one-to-two-week targeted range.

Total revenues also include Sanofi and Bayer collaboration revenues(5) of $638 million in the second quarter of 2019, compared to $501 million in the second quarter of 2018. The Company’s Antibody License and Collaboration Agreement with Sanofi achieved profitability in connection with commercialization of antibodies in the second quarter of 2019 for the first time. Consequently, Sanofi collaboration revenue in the second quarter of 2019 included the Company’s share of profits from collaboration antibodies of $39 million, while Sanofi collaboration revenue in the second quarter of 2018 included the Company’s share of losses from collaboration antibodies of $69 million. The increase was primarily driven by higher net product sales of Dupixent.

Refer to Table 4 for a summary of collaboration and other revenue.

Research and Development (R&D) Expenses: GAAP R&D expenses were $1.048 billion in the second quarter of 2019, compared to $529 million in the second quarter of 2018. The higher R&D expenses in the second quarter of 2019 were principally due to a $400 million up-front payment in connection with the collaboration agreement with Alnylam Pharmaceuticals, Inc. In the second quarter of 2019, R&D-related non-cash share-based compensation expense was $59 million, compared to $60 million in the second quarter of 2018.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $417 million in the second quarter of 2019, compared to $365 million in the second quarter of 2018. The higher SG&A expenses in the second quarter of 2019 were primarily due to higher headcount and related costs, and an increase in commercialization-related expenses for Dupixent. In the second quarter of 2019, SG&A-related non-cash share-based compensation expense was $38 million, compared to $41 million in the second quarter of 2018.

Cost of Goods Sold (COGS): GAAP COGS was $67 million in the second quarter of 2019, compared to $36 million in the second quarter of 2018. The increase in COGS was primarily due to the Company’s commercialization of Libtayo in the United States, including royalties to third parties and the Company’s obligation to pay Sanofi its share of Libtayo gross profits.

Other Income (Expense): GAAP other income (expense), net, in the second quarter of 2019 and 2018 includes the recognition of $117 million of net unrealized losses and $17 million of net unrealized gains, respectively, on equity securities.

Income Taxes: In the second quarter of 2019, GAAP income tax expense was $32 million and the effective tax rate was 14.1%, compared to $105 million and 16.0%, respectively, in the second quarter of 2018. The effective tax rate for the second quarter of 2019 was positively impacted, compared to the U.S. federal statutory rate, primarily by income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate, stock-based compensation, and federal tax credits for research activities.

GAAP and Non-GAAP Net Income(1): GAAP net income was $193 million, or $1.77 per basic share and $1.68 per diluted share, in the second quarter of 2019, compared to GAAP net income of $551 million, or $5.12 per basic share and $4.82 per diluted share, in the second quarter of 2018.

Non-GAAP net income was $690 million, or $6.32 per basic share and $6.02 per diluted share, in the second quarter of 2019, compared to non-GAAP net income of $624 million, or $5.79 per basic share and $5.45 per diluted share, in the second quarter of 2018.

The difference in GAAP net income and non-GAAP net income in the second quarter of 2019 was largely impacted by (i) the Alnylam up-front payment being recognized as GAAP R&D expense during the period and (ii) unrealized losses recorded in GAAP other income (expense) related to Alnylam common shares the Company purchased in connection with the collaboration agreement. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

2019 Financial Guidance(2)

The Company’s updated full year 2019 financial guidance consists of the following components:
GAAP Sanofi collaboration revenue: Sanofi reimbursement of Regeneron commercialization-related expense

This press release uses non-GAAP net income, non-GAAP net income per share, non-GAAP unreimbursed R&D, and non-GAAP SG&A, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and other items from the related GAAP financial measure. Non-GAAP adjustments also include the estimated income tax effect of reconciling items.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control (such as the Company’s stock price on the dates share-based grants are issued or changes in the fair value of the Company’s equity investments) or items that are not associated with normal, recurring operations. Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. A reconciliation of the Company’s historical GAAP to non-GAAP results is included in Table 3 of this press release.

The Company’s 2019 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release.

A reconciliation of full year 2019 non-GAAP to GAAP financial guidance is included below:

SG&A: Non-cash share-based compensation expense

Unreimbursed R&D represents R&D expenses reduced by R&D expense reimbursements from the Company’s collaborators and/or customers.

The Company’s collaborators provide it with estimates of the collaborators’ respective sales and the Company’s share of the profits or losses from commercialization of products for the most recent fiscal quarter. The Company’s estimates for such quarter are reconciled to actual results in the subsequent fiscal quarter, and the Company’s share of the profit or loss is adjusted on a prospective basis accordingly, if necessary.

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its second quarter 2019 financial and operating results on Tuesday, August 6, 2019, at 8:30 AM. To access this call, dial (800) 708-4540 (U.S.) or (847) 619-6397 (International). A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for 30 days.

On August 6, 2019 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company, reported that its manufacturing partner, Aldevron, has successfully completed the manufacturing of the TUSC2 (Tumor Suppressor Candidate 2) plasmid DNA pursuant to the manufacturing agreement between Genprex and Aldevron that was announced in September 2018 (Press release, Genprex, AUG 6, 2019, View Source [SID1234538218]).

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Genprex’s initial product candidate, Oncoprex consists of a TUSC2 plasmid DNA manufactured by Aldevron encapsulated in a nanovesicle made from lipid molecules with a positive electrical charge. Historically, the manufacturing steps of combining the plasmid DNA with the lipid nanovesicles of Oncoprex, has been done for Genprex at MD Anderson Cancer Center. Since Genprex’s IPO, the company has been working to transfer and scale up these processes through other contract manufacturers.

"Each successful release of plasmid DNA batches is an important milestone for Genprex as it allows us to not only demonstrate continued progress in coordinating scale-up manufacturing of Oncoprex, but it takes us one step closer to re-entering the clinic with both our EGFR program and our immunotherapy combination programs. Biologics manufacturing, especially for lipid nanoparticle (or LNP) delivered gene therapy, is a complex process, but one we tackle with pride alongside dedicated partners such as Aldevron, through a similar vision to deliver innovative therapies to patients with significant unmet medical needs," said Julien Pham, MD, Genprex’s President and Chief Operating Officer.

The U.S. Food and Drug Administration (FDA) has made manufacturing a top priority for cell and gene therapy companies. The FDA’s former Commissioner, Scott Gottlieb, noted in 2018 that the agency devotes approximately 80 percent of its focus during reviews of gene therapy candidates to manufacturing and quality concerns. FDA’s Director of the Center for Drug Evaluation and Research, Janet Woodcock, M.D., noted in July 2019 that the agency is adapting to the flood of new drug applications stemming from advances in gene therapy and is shifting its stance toward drug development more than in recent years. This shift emphasizes the need for gene therapy companies to not only demonstrate clinical efficacy but also be able to manufacture these drugs on a large scale.

Genprex has made manufacturing one of its top priorities since its IPO in 2018. During that time, Genprex has been building out its manufacturing process development to support this expansion and advance its commercial scaling capabilities.

Earlier this year, Genprex strengthened its senior team with the appointment of Eric Chapdelaine as Senior Director of Pharmaceutical Sciences and Manufacturing to support the company’s manufacturing, technical operations, and supply chain management.