On October 24, 2018 Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a leader in precision genetic medicine for rare diseases,reported financial results for the third quarter of 2018 (Press release, Sarepta Therapeutics, OCT 24, 2018, View Source [SID1234530290]).

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"We are pleased to report another positive quarter, delivering strong EXONDYS 51 sales and tracking to achieve our full-year sales objectives while both advancing our RNA pipeline and making substantial progress in the creation of an enduring gene therapy engine," stated Doug Ingram, Sarepta’s president and chief executive officer. "We continued this quarter to advance our RNA pipeline, PMOs and next-generation PPMO platform, with urgency. Further, the strides we have taken in service of our gene therapy engine, including unprecedented results in our micro-dystrophin program, rights to what are now 14 gene therapy programs, the addition of manufacturing partners, and the continued hiring of gene therapy talent, speak to our vision. Others may be content with steady progress. We see a revolution and it is our intention to lead that revolution to the benefit of countless genetic disease patients awaiting life-enhancing therapies."

Third Quarter 2018 and Recent Corporate Developments

Lysogene Agreement – Signed a license agreement with Lysogene, a biopharmaceutical company specializing in gene therapy targeting central nervous system (CNS) diseases, for the development of a gene therapy, LYS-SAF302, to treat Mucopolysaccharidosis type IIIA (MPS IIIA), also called Sanfilippo syndrome type A, a rare, severe and fatal inherited neurodegenerative lysosomal storage disorder. The pivotal gene therapy study is scheduled to start by year-end 2018; and the trial will assess the efficacy of LYS-SAF302 in improving or stabilizing the neurodevelopmental status of MPS IIIA patients. Sarepta receives full commercial rights to LYS-SAF302 in the U.S. and other markets outside of Europe, while Lysogene retains full commercial rights in Europe.

Exhibit 99.1

Paragon Bioservices Agreement – Entered into long-term manufacturing partnership with Paragon Bioservices, significantly expanding Sarepta’s commercial capacity for its micro-dystrophin gene therapy program, as well as bolstering the Company’s clinical and commercial capacity for its other pipeline programs.

Nationwide Children’s Hospital Gene Therapy Partnership, Charcot-Marie-Tooth (CMT) Neuropathy – Forged another agreement with Nationwide Children’s Hospital giving Sarepta the certain exclusive rights to the Nationwide Children’s gene therapy candidate, neurotrophin 3 (NT-3), to treat CMT neuropathies, including CMT type 1A. CMT is a group of hereditary, degenerative nerve diseases that can affect motor skills, resulting in muscle weakness, and limiting patients’ ability to walk or use their hands. CMT is the most common inherited neuromuscular disorder, affecting over 2.8 million people worldwide. A clinical trial is scheduled to begin in 2019 in the most prevalent subtype of CMT, CMT type 1A.

Positive Micro-Dystrophin Gene Therapy Clinical Results in DMD Patients Presented at the 23rd International Congress of the World Muscle Society (Mendoza, Argentina) – Jerry Mendell, M.D., of Nationwide Children’s, presented positive updated results from the gene therapy clinical trial assessing AAVrh74.MHCK7.micro-Dystrophin in individuals with Duchenne muscular dystrophy (DMD). Dr. Mendell’s presentation included positive results from the biopsy of the fourth patient showing robust micro-dystrophin expression as measured by Western blot and immunohistochemistry. In all patients, expression of micro-dystrophin was associated with significant expression and up regulation of the dystrophin-associated protein complex, an additional indication of functionality of dystrophin. All patients showed significant decreases of serum creatine kinase (CK) levels at last measure versus baseline, and positive functional improvements were shown across all measures. No serious adverse events (SAEs) were observed.

Clinical Hold Lifted for DMD Micro-dystrophin Gene Therapy Program – The Food and Drug Administration (FDA) lifted the clinical hold for Sarepta’s DMD micro-dystrophin gene therapy program. Sarepta previously announced on July 25, 2018 that the FDA placed the program on clinical hold due to the presence of trace amounts of DNA fragment in research-grade third-party supplied plasmid in a manufacturing lot. In response, and in collaboration with Nationwide Children’s, an action plan was developed and submitted to the FDA, including an audit of the plasmid supplier and a commitment to use GMP-s plasmid for all future production lots.

Exhibit 99.1

Negative CHMP Re-examination Opinion Received for Eteplirsen – The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) confirmed its May 31, 2018 negative opinion for a Conditional Marketing Application for eteplirsen. Relying upon CHMP advice and input, Sarepta will seek further scientific advice from the EMA on a possible path to bring eteplirsen to patients in Europe.

Conference Call

The Company will be hosting a conference call at 4:30 p.m. Eastern Time, to discuss Sarepta’s financial results and provide a corporate update. The conference call may be accessed by dialing 844-534-7313 for domestic callers and +1-574-990-1451 for international callers. The passcode for the call is 6099548. Please specify to the operator that you would like to join the "Sarepta Third Quarter 2018 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta’s website at www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta’s website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

Financial Results

On a GAAP basis, Sarepta reported a net loss of $76.4 million and $47.7 million, or $1.15 and $0.78 per basic and diluted share for the third quarter of 2018 and 2017, respectively. On a non-GAAP basis, the net loss for the third quarter of 2018 was $37.1 million, or $0.56 per basic and diluted share, compared to a net loss of $10.7 million for the same period of 2017, or $0.17 per basic and diluted share.

On a GAAP basis, for the nine months ended September 30, 2018, Sarepta reported a net loss of $221.0 million, or $3.38 per basic and diluted share, compared to a net loss of $26.7 million reported for the same period of 2017, or $0.47 per basic and diluted share. On a non-GAAP basis, the net loss for the nine months ended September 30, 2018 was $83.1 million, or $1.27 per basic and diluted share, compared to a net loss of $65.7 million for the same period of 2017, or $1.15 per basic and diluted share.

Net Revenues

For the three months ended September 30, 2018, the Company recorded net revenues of $78.5 million, compared to net revenues of $46.0 million for the same period of 2017, an increase of $32.5 million. For the nine months ended September 30, 2018, the Company recorded net revenues of $216.6 million,

Exhibit 99.1

compared to net revenues of $97.3 million for the same period of 2017, an increase of $119.3 million. The increases primarily reflect increasing demand for EXONDYS 51 in the U.S.

Cost and Operating Expenses

Cost of sales (excluding amortization of in-licensed rights)

For the three months ended September 30, 2018, cost of sales (excluding amortization of in-licensed rights) was $8.7 million, compared to $3.1 million for the same period of 2017. For the nine months ended September 30, 2018, cost of sales (excluding amortization of in-licensed rights) was $21.1 million, compared to $3.8 million for the same period of 2017. The increase primarily reflects royalty payments to BioMarin Pharmaceuticals (BioMarin) as a result of the execution of the settlement and license agreements with BioMarin in July 2017 as well as higher inventory costs related to increasing demand for EXONDYS 51 during 2018. In addition, prior to the approval of EXONDYS 51, the Company expensed related manufacturing and material costs as research and development expenses.

Research and development

Research and development expenses were $86.6 million for the third quarter of 2018, compared to $34.2 million for the same period of 2017, an increase of $52.4 million. The increase in research and development expenses primarily reflects the following:

$18.0 million increase in up-front and milestone payments. The Company made a milestone payment of $10.0 million to Myonexus Therapeutics (Myonexus) for the achievement of one of the development milestones. In addition, the Company expensed $8.0 million related to the purchase of license to develop, manufacture and commercialize a pre-clinical Pompe product candidate under a license agreement with Lacerta Therapeutics (Lacerta);

$12.8 million increase in clinical and manufacturing expenses primarily due to increased patient enrollment in the on-going ESSENCE trial as well as a ramp-up of manufacturing activities for golodirsen, our micro-dystrophin program and our PPMO platform. These increases were partially offset by a ramp-down of clinical trials in eteplirsen primarily because the PROMOVI trial has been fully enrolled;

$8.1 million increase in compensation and other personnel expenses primarily due to an increase in headcount;

$3.8 million increase in pre-clinical expenses primarily due to the continuing ramp-up of toxicology studies in our PPMO platform;

Exhibit 99.1

$2.6 million increase in facility-related expenses due to our continuing expansion efforts;

$2.6 million increase in sponsored research with institutions such as Duke University and Nationwide Children’s Hospital;

$1.6 million increase in collaboration cost sharing with Summit on its utrophin platform; and

$1.4 million increase in stock-based compensation expense primarily driven by increases in headcount and stock price.

Research and development expenses were $255.6 million for the nine months ended September 30, 2018, compared to $122.3 million for the same period of 2017, an increase of $133.3 million. The increase in research and development expenses primarily reflects the following:

$56.0 million increase in up-front and milestone payments. The Company made an up-front payment of $60.0 million to Myonexus upon execution of the warrant to purchase common stock agreement in May 2018 and a milestone payment of $10.0 million to Myonexus upon achievement of one of the development milestones in September 2018. In addition, the Company expensed $8.0 million related to the purchase of license to develop, manufacture and commercialize a pre-clinical Pompe product candidate under a license agreement with Lacerta. In May 2017, the Company made a milestone payment of $22.0 million to Summit as the milestone of the last patient dosed in the safety arm cohort to the PhaseOut DMD study was achieved;

$25.0 million increase in clinical and manufacturing expenses primarily due to increased patient enrollment in the on-going ESSENCE trial as well as a ramp-up of manufacturing activities for golodirsen, casimersen, our micro-dystrophin program and our PPMO platform. These increases were partially offset by a ramp-down of clinical trials in eteplirsen primarily because the PROMOVI trial has been fully enrolled;

$16.7 million increase in compensation and other personnel expenses primarily due to an increase in headcount;

$7.9 million increase in pre-clinical expenses primarily due to the continuing ramp-up of toxicology studies in our PPMO platform as well as golodirsen and casimersen;

$7.6 million increase in collaboration cost sharing with Summit on its utrophin platform;
rimarily due to continuing accelerated company growth as a result of expansion of our R&D pipeline;

$4.7 million increase in facility-related expenses due to our continuing expansion efforts;

Exhibit 99.1

$4.5 million increase in stock-based compensation expense primarily driven by increases in headcount and stock price as well as achievement of a milestone related to the September 2016 restricted stock awards with a performance condition; and $4.0 million increase in sponsored research with institutions such as Duke University, Genethon and Nationwide Children’s Hospital.

Non-GAAP research and development expenses were $64.2 million and $31.5 million for the third quarter of 2018 and 2017, respectively. Non-GAAP research and development expenses were $164.5 million and $92.2 million for the nine months ended September 30, 2018 and 2017, respectively.

Selling, general and administration

Selling general and administrative expenses were $53.0 million for the third quarter of 2018, compared to $28.2 million for the same period of 2017, an increase of $24.8 million. The increase in selling, general and administrative expenses primarily reflects the following:

$9.8 million and $1.7 million increase in professional services and facility-related expenses, respectively, primarily due to continuing global expansion;

$9.4 million increase in compensation and other personnel expenses primarily due to an increase in headcount; and

$3.0 million increase in stock-based compensation primarily due to increases in headcount and stock price.

Selling general and administrative expenses were $143.5 million for the nine months ended September 30, 2018, compared to $90.5 million for the same period of 2017, an increase of $53.0 million. The increase in selling, general and administrative expenses primarily reflects the following:

$23.1 million increase in compensation and other personnel expenses primarily due to an increase in headcount;

$21.8 million and $2.9 million increase in professional services and facility-related expenses, respectively, primarily due to continuing global expansion;

$11.9 million increase in stock-based compensation primarily due to increases in headcount and stock price, the achievement of a milestone related to the September 2016 restricted stock awards granted with a performance condition, as well as the impact of a revised forfeiture rate assumption for equity awards granted to officers and directors;

Exhibit 99.1

$4.8 million decrease in restructuring expenses due to the relief of cease-use liabilities as a result of the termination of the rental agreement for our Corvallis facility; and

$3.5 million decrease in severance expense as a result of termination of our former CEO in June 2017.

Non-GAAP selling, general and administrative expenses were $42.5 million and $22.2 million for the third quarter of 2018 and 2017, respectively. Non-GAAP selling, general and administrative expenses were $113.5 million and $67.5 million for the nine months ended September 30, 2018 and 2017, respectively.

EXONDYS 51 litigation and license charges

As a result of the execution of the settlement and license agreements with BioMarin in July 2017, the Company recognized litigation and license charges of $25.6 million and $28.4 million during the three and nine months ended September 30, 2017, respectively. There was no such a transaction in 2018.

Amortization of in-licensed rights

For the three and nine months ended September 30, 2018, the Company recorded amortization of in-licensed rights of approximately $0.2 million and $0.6 million, respectively. For both the three and nine months ended September 30, 2017, the Company recorded amortization of in-licensed rights of approximately $0.8 million.

Other (loss) income

Gain from sale of Priority Review Voucher

In connection with the completion of the sale of the Priority Review Voucher (PRV) in March 2017, the Company recorded a gain of $125.0 from sale of the PRV in the first quarter of 2017.

Interest (expense) income and other, net

For the three and nine months ended September 30, 2018, the Company recorded $7.0 million and $16.7 million, respectively, of interest expense and other, net. For the same periods of 2017, the Company recorded $0.2 million and $0.7 million, respectively, of interest income and other, net. The period over period unfavorable change primarily reflects the interest expense accrued on the convertible notes issued in November 2017 partially offset by interest income from higher balances of cash, cash equivalents and investments.

Cash, Cash Equivalents, Investments and Restricted Investment

Exhibit 99.1

The Company had approximately $793.9 million in cash, cash equivalents and investments as of September 30, 2018 compared to $1.1 billion as of December 31, 2017. The decrease is primarily driven by the use of cash to fund the Company’s ongoing operations during the first three quarters of 2018.

Use of Non-GAAP Measures

In addition to the GAAP financial measures set forth in this press release, the Company has included certain non-GAAP measurements. The non-GAAP loss is defined by the Company as GAAP net loss excluding interest expense/(income), income tax expense/(benefit), depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items. Non-GAAP research and development expenses are defined by the Company as GAAP research and development expenses excluding depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items. Non-GAAP selling, general and administrative expenses are defined by the Company as GAAP selling, general and administrative expenses excluding depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items.

1. Interest, tax, depreciation and amortization

Interest income and expense amounts can vary substantially from period to period due to changes in cash and debt balances and interest rates driven by market conditions outside of the Company’s operations. Tax amounts can vary substantially from period to period due to tax adjustments that are not directly related to underlying operating performance. Depreciation expense can vary substantially from period to period as the purchases of property and equipment may vary significantly from period to period and without any direct correlation to the Company’s operating performance. Amortization expense associated with in-licensed rights as well as patent costs are amortized over a period of several years after acquisition or patent application or renewal and generally cannot be changed or influenced by management.

2. Stock-based compensation expenses

Stock-based compensation expenses represent non-cash charges related to equity awards granted by Sarepta. Although these are recurring charges to operations, management believes the measurement of these amounts can vary substantially from period to period and depend significantly on factors that are not a direct consequence of operating performance that is within management’s control. Therefore, management believes that excluding these charges facilitates comparisons of the Company’s operational performance in different periods.

Exhibit 99.1

3. Restructuring expenses

The Company believes that adjusting for these items more closely represents the Company’s ongoing operating performance and financial results.

4. Other items

The Company evaluates other items of expense and income on an individual basis. It takes into consideration quantitative and qualitative characteristics of each item, including (a) nature, (b) whether the items relates to the Company’s ongoing business operations, and (c) whether the Company expects the items to continue on a regular basis. These other items include the aforementioned gain from the sale of the Company’s PRV and up-front and milestone payments.

The Company uses these non-GAAP measures as key performance measures for the purpose of evaluating operational performance and cash requirements internally. The Company also believes these non-GAAP measures increase comparability of period-to-period results and are useful to investors as they provide a similar basis for evaluating the Company’s performance as is applied by management. These non-GAAP measures are not intended to be considered in isolation or to replace the presentation of the Company’s financial results in accordance with GAAP. Use of the terms non-GAAP research and development expenses, non-GAAP selling, general and administrative expenses, non-GAAP other income and loss adjustments, non-GAAP income tax expense, non-GAAP net loss, and non-GAAP basic and diluted net loss per share may differ from similar measures reported by other companies, which may limit comparability, and are not based on any comprehensive set of accounting rules or principles. All relevant non-GAAP measures are reconciled from their respective GAAP measures in the attached table "Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures."

About EXONDYS 51

EXONDYS 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. EXONDYS 51 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

Important Safety Information About EXONDYS 51

Exhibit 99.1

Hypersensitivity reactions, including rash and urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, and hypotension, have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy.

Adverse reactions in DMD patients (N=8) treated with EXONDYS 51 30 or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended.

In the 88 patients who received ≥30 mg/kg/week of EXONDYS 51 for up to 208 weeks in clinical studies, the following events were reported in ≥10% of patients and occurred more frequently than on the same dose in Study 1: vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

On October 24, 2018 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the third quarter ended September 30, 2018 and reviewed recent progress with its approved and investigational medicines (Press release, Vertex Pharmaceuticals, OCT 24, 2018, View Source [SID1234530273]). Vertex also reiterated its guidance for full-year 2018 total CF product revenues and guidance for combined GAAP and non-GAAP R&D and SG&A expenses.

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We continue to make significant progress toward our goal of developing medicines for all people with CF as marked by the recent approvals of KALYDECO and ORKAMBI in younger children, the launch of SYMDEKO in the U.S. and the rapid progress we have made with our triple combination pivotal studies," said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. "In our development pipeline, we are advancing potential medicines for pain, sickle cell disease and beta thalassemia and are also beginning to advance additional compounds from research into early clinical development that could fundamentally change the treatment of other serious diseases in the future."

Dr. Leiden continued, "Our ability to treat more and more people with CF is driving revenue and earnings growth and significant cash flow generation, which enables the company to invest to discover and develop transformative future medicines for the treatment of CF and other life-threatening diseases."

Combined non-GAAP R&D and SG&A expenses increased compared to the third quarter of 2017 due to the advancement of the company’s portfolio of triple combination regimens for CF and investments to support the treatment of CF globally.
Combined GAAP R&D and SG&A expenses decreased compared to the third quarter of 2017 due to an upfront payment of $160.0 million related to the acquisition of VX-561, an investigational once-daily CFTR potentiator, from Concert Pharmaceuticals in the third quarter of 2017, partially offset by expenses related to the advancement of the company’s portfolio of triple combination regimens for CF and investments to support the treatment of CF globally.

Third-Quarter 2018 Net Income and Cash Position

Non-GAAP net income increased 107% compared to the third quarter of 2017 largely driven by the strong growth in total CF product revenues.
GAAP net income increased compared to the third quarter of 2017 largely driven by the strong growth in total CF product revenues and by a reduction to research and development expenses due to the $160.0 million payment to Concert in the third quarter of 2017.

Cash, cash equivalents and marketable securities as of September 30, 2018 were approximately $3.1 billion, an increase of approximately $1.0 billion compared to $2.1 billion as of December 31, 2017.

2018 Financial Guidance
Vertex today reiterated its full-year 2018 total CF product revenue guidance and guidance for combined GAAP and non-GAAP R&D and SG&A expenses as summarized below:

"We have created a strong financial profile for our business and are poised for continued growth as we make progress developing medicines for many more people with CF," said Ian Smith, Executive Vice President and Chief Operating Officer. "Nearer term, we anticipate revenue growth in 2019 will be driven by the impact of the SYMDEKO and SYMKEVI launches and recently completed reimbursement agreements and label expansions for our CF medicines. The potential for additional revenue growth in 2019 will be dependent upon gaining new reimbursement agreements in key countries, including the UK and France. Continued growth beyond 2019 will be driven by the potential approval, reimbursement and uptake of a triple combination medicine for the large number of patients with a minimal function mutation who currently do not have a treatment for the cause of their CF."

Business Highlights

TRIPLE COMBINATION REGIMENS

Bringing triple combination regimens to people with CF as quickly as possible
•
Data are expected in late 2018 for the two Phase 3 studies of VX-659 in triple combination with tezacaftor and ivacaftor in people with CF who have one F508del mutation and one minimal function mutation and in people who have two F508del mutations.
•
Enrollment is expected to be complete in the fourth quarter of 2018 for the two Phase 3 studies of VX-445 in triple combination with tezacaftor and ivacaftor in people with CF who have one F508del mutation and one minimal function mutation and in people who have two F508del mutations. The company plans to report data from these studies in the first quarter of 2019.
•
Vertex plans to evaluate data from both the VX-659 and VX-445 Phase 3 triple combination programs to choose the best regimen to submit for potential regulatory approval. Together these data are expected to provide the basis for submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for people who have one F508del mutation and one minimal function mutation no later than mid-2019.

Evaluating VX-659 and VX-445 in children
•
Studies are underway to evaluate both the VX-659 and VX-445 triple combination regimens in children with CF ages 6 through 11 who have one F508del mutation and one minimal function mutation and in children who have two F508del mutations. These studies are intended to support potential approval of a triple combination regimen in children ages 6 through 11.

Potential once-daily regimens
•
In early 2018, the company reported positive safety and efficacy results for the once-daily potentiator VX-561 when dosed as part of a triple combination regimen including VX-659 or VX-445 and tezacaftor. The once-daily triple combination regimens were generally well tolerated, and the majority of adverse events were mild to moderate.

Based on recent feedback from the FDA, Vertex plans to initiate a Phase 2 study in the first half of 2019 evaluating VX-561 as a monotherapy in people with CF who have a gating mutation.

SYMKEVI in the European Union
•
On July 27, 2018, Vertex announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for SYMKEVI (tezacaftor/ivacaftor) in a combination regimen with ivacaftor (KALYDECO) for the treatment of people with CF ages 12 and older who either have two copies of the F508del mutation or who have one copy of the F508del mutation and a copy of one of the following 14 mutations in which the CFTR protein shows residual activity: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.
•
Approval for SYMKEVI in the European Union (EU) is expected in the fourth quarter of 2018.

APPROVED CF MEDICINES
Establishing long-term reimbursement outside of the U.S.
•
On October 1, 2018, Vertex announced that it had entered into an innovative access contract with the Danish pharmaceutical and procurement organization, Amgros. This agreement provides eligible Danish CF patients access to all of Vertex’s current and future CF medicines. An agreement in Austria was also recently secured to provide access to ORKAMBI for all people with CF ages 6 through 11 who have two copies of the F508del mutation.
•
In September 2018, Vertex announced a reimbursement agreement in Australia for the use of ORKAMBI in people with CF ages 6 and older who have two copies of F508del mutation. A pathway to access for future Vertex CF medicine, tezacaftor/ivacaftor, was also established as part of this process.

Treating patients at younger ages with CFTR modulators: The company continues to make significant progress toward gaining approval for its CF medicines to be used earlier in the course of disease progression. Recent highlights include:
•
Vertex plans to submit a supplemental New Drug Application (sNDA) to the FDA in late 2018 based on positive data from a recently completed 24-week single-arm Phase 3 safety study of tezacaftor/ivacaftor in 70 children ages 6 through 11 who have two copies of the F508del mutation or who have one copy of the F508del mutation and one residual function mutation. The primary endpoint of the study was safety. The study met its primary safety endpoint, and safety data from the study showed that the treatment was generally well tolerated and safety data were consistent with those seen in previous Phase 3 studies of tezacaftor/ivacaftor in children ages 12 and older. To support approval in the EU, an eight-week, double-blind, placebo-controlled Phase 3 efficacy study is ongoing to evaluate tezacaftor/ivacaftor in approximately 65 children ages 6 through 11. The primary endpoint of this study is the absolute change in lung clearance index.
•
KALYDECO was approved in August 2018 in the U.S. for children with CF ages 12 to <24 months. On October 19, 2018, Vertex announced that it received a positive opinion from the European CHMP for KALYDECO in this age group. The company expects a decision in the EU in late 2018.
•
On October 18, 2018, Vertex announced positive data from a Phase 3 study evaluating ivacaftor in infants ages 6 to <12 months. These are the first data to demonstrate the potential to treat the underlying cause of CF in patients as young as six months old. The company plans to submit an sNDA to the FDA and a line extension to the EMA in late 2018.
•
ORKAMBI was approved in August 2018 in the U.S. for children with CF ages 2 to 5 years old. A line extension has been submitted to the EMA with a decision anticipated in the first half of 2019.
•
Dosing is underway in Phase 3 study evaluating lumacaftor/ivacaftor in children ages 12 to <24 months.

LATE-STAGE RESEARCH & CLINICAL DEVELOPMENT

Vertex continues to invest to discover and develop transformative medicines in other serious diseases. The company has a portfolio of potential medicines across a range of diseases, including:

Sickle Cell Disease & β-Thalassemia: Vertex and its partner CRISPR Therapeutics are developing the autologous gene-edited hematopoietic stem cell therapy CTX001 for the treatment of β-thalassemia and sickle cell disease.
•
In the U.S., Vertex and CRISPR Therapeutics recently announced that the FDA lifted the clinical hold on the CTX001 Investigational New Drug application (IND) for the treatment of sickle cell disease that was submitted earlier this year. The companies previously received regulatory approval to conduct a Phase 1/2 study in multiple countries in Europe and Canada. Vertex and CRISPR plan to initiate the study in sickle cell disease by the end of 2018. The first two patients in the study will be dosed sequentially and, pending data from these initial two patients, subsequent patients can be dosed concurrently.
•
Enrollment for a Phase 1/2 study in people with β-thalassemia is currently open at multiple clinical trial sites in Europe, and the first patient has now enrolled in this study. The Phase 1/2 trial is designed to assess safety and efficacy in adult transfusion-dependent non-beta zero/beta zero β-thalassemia patients. Similar to the study in sickle cell disease, the first two patients in the study will be dosed sequentially and, pending data from these initial two patients, subsequent patients can be dosed concurrently. This study is designed to enroll up to 45 patients.

Pain: Potential Role of Nav1.8 Inhibition
•
The company is planning to initiate a Phase 2b dose-ranging study evaluating the Nav1.8 inhibitor VX-150 using an oral formulation in patients with acute pain following bunionectomy surgery. The study is designed to evaluate multiple oral doses of VX-150 to potentially support pivotal development in acute pain.
•
Enrollment is complete in a Phase 2 proof-of-concept study evaluating VX-150 for the treatment of pain caused by small fiber neuropathy, and data are expected in early 2019.

Vertex continues to invest to discover other potential pain molecules that target the sodium channel 1.8 (Nav1.8) and other new mechanisms.

Alpha-1 Antitrypsin Deficiency (AAT)
•Vertex has advanced multiple small molecule correctors of AAT through preclinical development and is preparing to initiate clinical development for the first of these potential medicines by the end of 2018. AAT is a genetic disorder that is caused by mutations in a single gene that result in life-shortening systemic complications, primarily in the lung and liver.

Acute Spinal Cord Injury

In October 2014, VRTX in-licensed VX-210 (Cethrin) from BioAxone BioSciences, Inc. as a potential new treatment for spinal cord injury. An interim analysis of a Phase 2b study evaluating VX-210 in patients with certain acute cervical spinal cord injuries was recently conducted and based on the available data, the study’s Data Safety Monitoring Board (DSMB) recommended to stop the study early due to futility. There were no safety concerns noted in the DSMB’s review of the data. Based on the DSMB’s recommendation and Vertex’s review of the data, the company has decided to stop all development of VX-210, and will terminate the Phase 2b study. Vertex will discuss with BioAxone the next steps for the program.

On October 24, 2018 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) reported that members of the Company’s executive team will attend the BIO-Europe 24th Annual International Partnering Conference in Copenhagen, Denmark on November 5-7, 2018 (Press release, Actinium Pharmaceuticals, OCT 24, 2018, View Source [SID1234530261]). BIO-Europe is the largest life science partnering event in Europe that is expected to draw over 4,000 attendees from over 2,000 companies.

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Actinium is developing Antibody Radio-Conjugates (ARCs) that deliver radioisotopes in a targeted manner to cells expressing CD45 and CD33 for multiple hematologic indications. Actinium is the only company with multi-disease, multi-target pipeline focused on improving access and outcomes to cellular therapies including bone marrow transplant and CAR-T through targeted conditioning. Actinium’s lead targeted conditioning product candidate, Iomab-B, is currently being studied in a pivotal Phase 3 trial. Actinium’s best-in-class CD33 program is being studied in multiple trials as both a targeted conditioning agent and therapeutic for patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome and Multiple Myeloma. Underpinning Actinium’s clinical programs is its Antibody Warhead Enabling technology that has been studied in both hematologic and solid tumors, which could be utilized to create ARCs for numerous targets and indications.

Sandesh Seth, Actinium’s Chairman and Chief Executive Officer said, "We are particularly excited for this year’s BIO-Europe Partnering Conference for a multitude of reasons. Given the progress and expansion of our targeted conditioning pipeline combined with the strong interest for radiopharmaceutical therapies of late, we look forward to what we expect to be a productive and valuable conference. First and foremost, we will be able to highlight extensive clinical data from our highly differentiated CD45 and CD33 ARCs for targeted conditioning and therapeutic indications, which have been studied in over 600 patients across 14 clinical trials. We will also showcase our recently unveiled Iomab-ACT program that we intend to make a universally available next generation lymphodepletion solution prior to CAR-T therapy. Additionally, we will present our AWE technology platform to potential collaborators and partners just as we have with our established AWE collaborator Astellas Pharma, Inc."

Conference attendees may schedule a meeting with Actinium’s management through the conference’s partnering system View Source or by contacting Steve O’Loughlin, Actinium’s Principal Financial Officer, [email protected].

About BIO-Europe

The 24th annual BIO-Europe is Europe’s largest partnering conference serving the global biotechnology industry. Delegates from all parts of the biotechnology value chain come to BIO-Europe to quickly identify, engage and enter strategic relationships that drive their businesses successfully forward. Investment and collaboration opportunities developed in prior BIO-Europe conferences have produced many highly successful business partnerships. BIO-Europe is organized by EBD Group, the leading partnering firm for the global biotechnology industry, in alliance with the Biotechnology Industry Organization (BIO)

On October 24, 2018 Melinta Therapeutics, Inc., (NASDAQ: MLNT), a commercial-stage company discovering, developing and commercializing novel antibiotics to treat serious bacterial infections, reported that its board of directors has appointed John H. Johnson as interim chief executive officer (CEO), effective immediately (Press release, Cempra, OCT 24, 2018, View Source [SID1234530248]). Mr. Johnson, a director of Melinta, succeeds Dan Wechsler, who is stepping down from his role as president, CEO and director to pursue other opportunities. The Board and Mr. Wechsler mutually agreed that now is the right time to transition leadership of the Company.

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"John is an accomplished biopharmaceutical industry leader with more than 20 years of direct expertise in the antibiotics space, and we are pleased that he is leading Melinta during this pivotal time. Under John’s leadership, we are confident that sales of commercial products, Baxdela (delafloxacin), Vabomere (meropenem and vaborbactam), Orbactiv (oritavancin), and Minocin (minocycline) for Injection, will continue to accelerate, and that he will focus on strengthening the financial position of Melinta by optimizing the integrations of the infectious disease business of The Medicines Company and Cempra," said Kevin Ferro, chairman of Melinta Therapeutics.

"I am pleased to serve as interim CEO of Melinta and will continue to work closely with the board of directors, executive management and the broader team to further advance the Company’s mission to provide life-saving therapeutic solutions that address the evolving global threat of bacterial infections and antibiotic resistance. This is an exciting time for Melinta and I look forward to contributing to the continued growth and future success of the Company by delivering anti-infective solutions to patients," said John H. Johnson, interim chief executive officer and director of Melinta Therapeutics.

Mr. Ferro added, "On behalf of the board of directors, we would like to thank Dan for his contributions to the Company and we wish him well in his future endeavors."

John H. Johnson has more than 30 years of biopharmaceutical industry, executive leadership and commercial experience at leading global organizations, including Johnson & Johnson, Eli Lilly & Company, ImClone and Pfizer, Inc. In addition to Melinta, Mr. Johnson currently serves on the boards of Aveo Oncology, Histogenics Corporation, Portola Pharmaceuticals, Inc., and is chairman of Strongbridge Biopharma plc. Mr. Johnson previously served as a director at Cempra and Sucampo. He also previously served as president and chief executive officer of Dendreon Corporation from February 2012, became chairman in July 2013, and served as chairman until June 2014 and president and chief executive officer until August 2014. Prior to this role, Mr. Johnson served as president of Eli Lilly & Company’s Global Oncology Unit following the company’s 2008 acquisition of ImClone Systems Incorporated, where he served as chief executive officer and on ImClone’s board. Prior to ImClone, Mr. Johnson served as the company group chairman of biopharmaceuticals within Johnson & Johnson, where he was responsible for biotechnology, immunology and oncology commercial business units. Prior to that role, he held several executive

positions at Johnson & Johnson, Parkstone Medical Information Systems, Inc., Ortho-McNeil Pharmaceutical Corporation and Pfizer Inc. While at Ortho-McNeil, Mr. Johnson was responsible for the company’s anti-infectives portfolio. During his career, Mr. Johnson also served as a member of the board of directors of Pharmaceutical Research and Manufacturers of America (PhRMA), the Health Section Governing Board of Biotechnology Industry Organizations (BIO), and BioNJ.

On October 24, 2018 Agilent Technologies Inc. (NYSE: A) reported that it will release fourth-quarter fiscal 2018 financial results after the stock market closes on November 19 (Press release, Agilent, OCT 24, 2018, http://www.agilent.com/about/newsroom/presrel/2018/24oct-gp18056.html [SID1234530244]). The company will host a live webcast of its investor conference call in listen-only mode.

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Date: Monday, November 19, 2018
Time: 1:30 PM (Pacific Time)
Web access: http://www.investor.agilent.com

Listeners may log on and select "Q4 2018 Agilent Technologies Inc. Earnings Conference Call" in the "News & Events — Calendar of Events" section. The webcast will remain on the company site for 90 days.

In addition, a telephone replay of the conference call will be available at approximately November 19, 2018 at 4: 30 PM (Pacific Time) after the call and through November 26 by dialing +1 855-859-2056 (or +1 404-537-3406 from outside the United States) and entering pass code 6519506.