On August 1, 2019 Savara Inc. (NASDAQ: SVRA), an orphan lung disease company, reported that the Company will report second quarter 2019 financial results and provide a business update on Thursday, August 8, 2019 (Press release, Savara, AUG 1, 2019, View Source [SID1234538035]). Savara management will host a conference call at 4:30 p.m. Eastern Time (ET)/1:30 p.m. Pacific Time (PT).

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Shareholders and other interested parties may access the conference call by dialing (855) 239-3120 from the U.S., (855) 669-9657 from Canada, and (412) 542-4127 from elsewhere outside the U.S. and request the "Savara Inc." call. A live webcast of the conference call will be available online in the Investors section of Savara’s website at View Source

Approximately one hour after the call, a replay of the webcast will be available on Savara’s website for 30 days, and a telephone replay will be available through August 15, 2019 by dialing (877) 344-7529 from the U.S., (855) 669-9658 from Canada and (412) 317-0088 from elsewhere outside the U.S. and entering the replay access code 10133438.

On August 1, 2019 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended June 30, 2019 and provided a corporate update (Press release, DURECT, AUG 1, 2019, https://www.prnewswire.com/news-releases/durect-corporation-announces-second-quarter-2019-financial-results-and-update-of-programs-300895291.html [SID1234538051]).

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Total revenues were $4.0 million and net loss was $7.2 million for the three months ended June 30, 2019 as compared to total revenues of $3.4 million and net loss of $7.0 million for the three months ended June 30, 2018.
At June 30, 2019, cash and investments were $38.1 million, compared to cash and investments of $34.5 million at December 31, 2018. Subsequent to the end of the quarter, in July DURECT received a $25 million payment from Gilead relating to an exclusive license agreement for DURECT’s SABER technology. Debt at June 30, 2019 was $20.8 million, which included partial accrual for the final payment of our term loan.
"The second quarter was very productive, with multiple important milestones achieved, including announcing compelling preliminary data from the first 10 alcoholic hepatitis (AH) patients, announcing that the preliminary data from the completed 90 mg severe cohort was consistent with the first 10 patients, and proceeding to the 150 mg severe cohort in the ongoing DUR-928 alcoholic hepatitis trial," stated James E. Brown, D.V.M., President and CEO of DURECT. "We also successfully submitted a full response to the POSIMIR CRL seeking FDA approval, and received a user fee goal date for FDA response of December 27, 2019. In addition, in July we executed an exclusive license agreement with Gilead for a long-acting injectable HIV investigational product utilizing DURECT’s SABER technology, entailing an upfront fee of $25 million, up to $145 million in additional milestone payments plus royalties and an exclusive option to license additional SABER-based products directed to HIV and HBV for an additional $150 million per product in upfront and milestones plus royalties."

Update on Selected Programs and Transactions:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, first-in-class small molecule, which may have broad applicability in acute organ injuries such as AH and acute kidney injury (AKI), in chronic liver diseases such as non-alcoholic steatohepatitis (NASH), and in inflammatory skin disorders such as psoriasis and atopic dermatitis.

Clinical Trials

Alcoholic Hepatitis (AH)

As reported on May 7 and 8, 2019 through a press release and key opinion leader conference call, preliminary clinical data from the first 10 AH patients dosed with DUR-928 demonstrated statistically significant reductions from baseline of serum bilirubin levels and MELD scores. Additionally, Lille scores in patients treated with DUR-928 were statistically lower than historical controls. DUR-928 was well tolerated and PK parameters were not affected by the severity of the disease.
In June, we completed dosing the 90 mg cohort (n=4) in severe AH patients and, following approval by the Dose Escalation Committee (DEC), initiated dosing for the 150 mg cohort in severe AH patients. Preliminary data from the 90 mg severe cohort was consistent with the first 10 patients.
We are now enrolling moderate AH patients in the 90 mg cohort and severe AH patients in the 150 mg cohort.
About the AH Trial: DURECT is conducting a Phase 2a clinical trial with intravenously administered DUR-928 in patients with AH. This is an open label, dose escalation (30, 90 and 150 mg), multi-center U.S. study that includes patients with moderate and severe AH (as determined by initial MELD score). Dose escalation requires approval by the Dose Escalation Committee (DEC) following its review of safety and pharmacokinetic (PK) results from the prior dose level. The target number of patients for the study is 4 moderate and 4 severe per dose. The objectives of this study include assessment of safety, PK and pharmacodynamic (PD) signals, including liver chemistry, and biomarkers. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier 03432260.
In parallel with our ongoing trial, we are supporting Professor Craig McClain, MD (Chief of Research Affairs, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville) in his efforts to initiate an NIH-funded study of DUR-928 in AH patients at the University of Louisville.
AH is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol, and encompasses a spectrum that ranges from mild injury to severe, life threatening liver damage. The prevalence of AH is estimated to occur in 10-35% of heavy drinkers. According to an article in the Journal of Clinical Gastroenterology (2015 July; 49(6):506-511), there were over 320,000 hospitalizations related to alcoholic hepatitis in the U.S. in 2010, resulting in hospitalization costs of nearly $50,000 per patient. The cost of a liver transplant exceeds $800,000.
Non-Alcoholic Steatohepatitis (NASH)

In March 2019, we began enrolling patients in a Phase 1b randomized and open-label clinical study being conducted in the U.S. to evaluate safety, pharmacokinetics and signals of biological activity of DUR-928 in NASH patients with stage 1-3 fibrosis. DUR-928 (at doses of 50 mg QD, 150 mg QD or 300 mg BID) is administered orally for 28 consecutive days with approximately 20 patients per dose group for a total of approximately 60 patients in the trial.
Key endpoints include safety and PK, clinical chemistry and biomarkers (e.g., bilirubin, lipids, liver enzymes, CK-18s, and inflammatory cytokines) as well as liver imaging (e.g., MRI-PDFF).
We expect to announce initial data from this study in the second half of 2019.
In the Company’s previous Phase 1b NASH study, reported at the European Association for the Study of the Liver (EASL) in April 2017, an exploratory biomarker analysis demonstrated that a single oral dose of DUR-928 in NASH patients, at both dose levels tested (50 mg and 200 mg), resulted in statistically significant reductions from baseline of both full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP and IL-18.
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in both children and adults. It is estimated that NAFLD affects about 30% to 40% of adults and 10% of children in the United States. NASH, a more severe and progressive form of NAFLD, is one of the most common chronic liver diseases worldwide, with an estimated prevalence of more than 10% of adults in the United States, Europe, Japan and other developed countries. No drug is currently approved for NAFLD or NASH.
Psoriasis

We are conducting a Phase 2a, randomized, double-blind, vehicle-controlled proof-of-concept clinical trial, in which DUR-928 is applied topically once-daily for four weeks in patients with mild to moderate plaque psoriasis. The trial is being conducted at multiple clinical sites in the U.S. Twenty patients are planned to be enrolled to obtain approximately 15 evaluable patients. Patients serve as their own controls, applying DUR-928 to the plaque on one arm and the vehicle to a similar plaque on the other arm. After the treatment period, patients are followed for an additional four weeks. The primary efficacy endpoint is the change in local psoriasis scores from baseline in the DUR-928-treated plaques compared to that in the vehicle-treated plaques. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier 03837743.
We began enrolling patients in March of 2019 and expect to announce top line data from this study in the second half of 2019.
We previously conducted an exploratory Phase 1b trial in psoriasis patients (9 evaluable patients) in Australia. The trial was randomized, double-blinded, placebo and self-controlled, using a micro-plaque assay with intralesional injections of DUR-928. The results were encouraging and warranted advancing into the current proof-of-concept trial with topically applied DUR-928. In support of the Phase 2a study, we have completed multiple non-clinical safety studies for topically applied DUR-928.
Psoriasis is an inflammatory skin disease and an immune-mediated condition that causes the body to make new skin cells in days rather than weeks. Psoriasis affects an estimated 7.5 million Americans. According to the International Federation of Psoriasis Associations (IFPA), nearly 3% of the world’s population, or about 125 million people, has some form of psoriasis. Psoriasis causes itchiness and irritation and may be painful. There is no cure, but currently approved treatment can ease symptoms. Approximately 80% of patients with psoriasis have localized disease, which can be treated with topical therapies. As such, topical agents remain the mainstay of psoriasis treatment.
POSIMIR (bupivacaine extended-release solution) Post-Operative Pain Relief Depot. POSIMIR is our investigational post-operative pain relief depot that utilizes our patented SABER technology and is designed to deliver bupivacaine to provide up to 3 days of pain relief after surgery.

After a comprehensive review of the POSIMIR program in light of the issues raised by the FDA in our communications with them, including the Complete Response Letter (CRL), we prepared and submitted a full response to the CRL in late June 2019 intending to address the issues raised in the CRL and seeking FDA approval of POSIMIR.
The FDA has agreed to file the submitted response to the CRL as a complete Class 2 Resubmission and assigned a user fee goal date of December 27, 2019.
The effort to evaluate the program, develop a strategy for filing the response, and the actual writing of key sections of the response, has been under the direction of Dr. Lee Simon, who was formerly FDA’s Division Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug Products.
We believe that the completed inguinal hernia and subacromial decompression (shoulder) clinical trials support the efficacy of POSIMIR in post-operative pain and meet the requirements to be considered as adequate and well-controlled pivotal clinical trials. Both trials demonstrated a significant decrease in pain and opioid use over the 0-72 hour period following surgery as compared to placebo.
We have completed 16 clinical trials in the POSIMIR program, involving over 1,400 patients, over 850 of whom received POSIMIR with the remainder in control groups. We believe this is a sufficiently sized safety database. We believe that, with the PERSIST safety data from over 380 patients included, we now have sufficient data to address FDA’s issues raised in the CRL and that the data package meets the requirements for FDA approval.
POSIMIR has not been approved by the FDA for marketing in the U.S. for any indication and there can be no assurance that FDA will approve the planned submission described above.
Gilead Agreement. In July 2019, we entered into an agreement with Gilead Sciences, Inc. (Gilead) granting Gilead the exclusive worldwide rights to develop and commercialize a long-acting injectable HIV investigational product utilizing our SABER technology. Gilead also received exclusive access to the SABER platform for HIV and Hepatitis B Virus (HBV) and the exclusive option to license additional SABER-based products directed to HIV and HBV. Under the terms of the agreement, Gilead made an upfront payment to us of $25 million, with the potential for up to an additional $75 million in development and regulatory milestones, up to an additional $70 million in sales based milestones, as well as tiered royalties on product sales. Gilead has the exclusive option to license additional SABER-based products directed to HIV and HBV for an additional $150 million per product in upfront, development, regulatory and sales based milestones as well as tiered royalties on sales. The parties will collaborate on specified development activities with Gilead controlling and funding the development programs.

Indivior Agreement and PERSERIS. In September 2017, we entered into a patent purchase agreement with an affiliate of Indivior PLC, whereby we assigned certain of our U.S. patent rights to Indivior. Under the terms of the agreement, Indivior paid us $12.5 million upfront and a $5 million milestone based on NDA approval of PERSERIS (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults. We also receive quarterly earn-out payments based on a single digit percentage of U.S. net sales for certain products covered by the patent rights, including PERSERIS. The patent rights include granted patents extending into at least 2026.

According to its public disclosures, Indivior has stated that:
The PERSERIS commercial launch took place in the last week of February 2019 with a field force of 50 representatives.
As of Indivior’s July 31, 2019 update on the first half of 2019:
Net revenue was consistent with Indivior’s expectations
Managed care coverage is over 70% nationally, which is at parity with established LAIs
Sales key performance indicators (KPIs) (reach and frequency) are on target
Continued positive patient and HCP feedback
Indivior previously announced a peak annual net revenue goal for PERSERIS of $200 to $300 million.
U.S. sales of long acting injectables to treat schizophrenia were in excess of $3 billion in 2017.
Full prescribing information for PERSERIS, including BOXED WARNING, and Medication Guide can be found at www.perseris.com.
Financing. In June 2019, we raised net proceeds of approximately $15.0 million in a registered offering of the Company’s common stock.

Earnings Conference Call
We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss second quarter 2019 results and provide a corporate update:

Toll Free:

877-407-0784

International:

201-689-8560

Conference ID:

13692344

Webcast:

View Source

A live audio webcast of the presentation will be also available by accessing DURECT’s homepage at www.durect.com and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.

On August 1, 2019 La Jolla Pharmaceutical Company (Nasdaq: LJPC), a leader in the discovery, development and commercialization of innovative therapies intended to significantly improve outcomes in patients suffering from life-threatening diseases, reported financial results for the three and six months ended June 30, 2019 and highlighted recent corporate progress (Press release, La Jolla Pharmaceutical, AUG 1, 2019, View Source [SID1234538315]).

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Recent Corporate Progress

GIAPREZATM (angiotensin II)

Net Sales: For the three months ended June 30, 2019, GIAPREZA net sales were $5.7 million, up 258% from the same period in 2018, and up 30% from the three months ended March 31, 2019. For the six months ended June 30, 2019, GIAPREZA net sales were $10.1 million, up 320% from the same period in 2018.

Positive CHMP Opinion: In June 2019, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for La Jolla’s Marketing Authorisation Application (MAA) for GIAPREZA for the treatment of refractory hypotension in adults with septic or other distributive shock. The CHMP’s positive opinion was sent to the European Commission (EC), which has the authority to approve medicines for the 28 European Union member countries. Approval would also be recognized in Iceland, Norway and Liechtenstein. We expect a final approval decision on the GIAPREZA MAA by the EC in the third quarter of 2019.

Investigational Products

Breakthrough Therapy Designation and Orphan Drug Designation Received from the FDA for LJPC-0118 (artesunate): The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation and Orphan Drug designation for LJPC-0118 for the treatment of malaria in April 2019 and July 2019, respectively. The active pharmaceutical ingredient in LJPC-0118, artesunate, was demonstrated to be superior to quinine in reducing mortality in patients with severe falciparum malaria infection in two randomized, controlled, clinical studies. We plan to file a New Drug Application (NDA) for LJPC-0118 with the FDA in the fourth quarter of 2019.

Positive Results Announced from Pre-Specified Interim Analysis of Phase 2 Study of LJPC-401 in Patients with Hereditary Hemochromatosis: In June 2019, we announced positive results from the pre-specified interim analysis of our Phase 2 study of LJPC-401 (synthetic human hepcidin) in patients with hereditary hemochromatosis (HH). The interim analysis of efficacy included 26 patients who had reached the end of the 16-week treatment period, and the interim analysis of safety included 60 randomized patients. Treatment with LJPC-401 resulted in a statistically significant reduction in transferrin saturation (TSAT) from baseline to the end of treatment (16 weeks), the primary efficacy endpoint of the study: LJPC‑401‑treated patients had a mean reduction in TSAT of 42% compared to placebo-treated patients who had a mean reduction of 6% (p<0.0001). The requirement for and frequency of phlebotomy procedures, a key secondary endpoint of the study, also was statistically significant: LJPC-401-treated patients had 0.06 phlebotomies per month compared to placebo-treated patients who had 0.41 phlebotomies per month (p=0.003). There were 3 phlebotomies in 2 LJPC-401-treated patients and 24 phlebotomies in 9 placebo-treated patients. LJPC-401 was well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were injection site reactions (ISRs). The ISRs were all mild or moderate in severity, and no ISRs resulted in treatment discontinuation. As of the interim analysis, there were no serious TEAEs reported. We expect to announce top-line results of LJ401-HH01 in the fourth quarter of 2019.

"We are pleased with the progress made in the first half of 2019, which included the achievement of significant milestones for each of GIAPREZA, LJPC-0118 and LJPC-401," said George Tidmarsh, M.D., Ph.D., La Jolla’s President and Chief Executive Officer. "In the second half of 2019, we look forward to continued growth in GIAPREZA net sales, the final approval decision

on the GIAPREZA MAA by the EC, our filing of an NDA for LJPC-0118 with the FDA and top-line results of our Phase 2 study of LJPC-401 in patients with HH."

Financial Results

For the three and six months ended June 30, 2019, GIAPREZA net sales were $5.7 million and $10.1 million, respectively, compared to $1.6 million and $2.4 million, respectively, for the same periods in 2018. La Jolla’s net loss for the three and six months ended June 30, 2019 was $30.4 million and $62.1 million, or $1.12 per share and $2.29 per share, respectively, compared to $52.8 million and $103.3 million, or $2.02 per share and $4.22 per share, respectively, for the same periods in 2018. La Jolla continues to expect full-year 2019 GIAPREZA net sales of $24 million to $28 million.

As of June 30, 2019, La Jolla had $123.4 million in cash, compared to $172.6 million as of December 31, 2018. Net cash used in operating activities for the three and six months ended June 30, 2019 was $16.5 million and $49.2 million, respectively, compared to $37.5 million and $83.4 million, respectively, for the same periods in 2018. La Jolla has no debt. La Jolla continues to expect that its net cash used in operating activities in 2019 will be $89 million to $94 million.

About GIAPREZA

In December 2017, GIAPREZA (angiotensin II) was approved by the U.S. Food and Drug Administration (FDA) as a vasoconstrictor indicated to increase blood pressure in adults with septic or other distributive shock. GIAPREZA mimics the body’s endogenous regulatory peptide that is central to the renin-angiotensin-aldosterone system to increase blood pressure. Prescribing information for GIAPREZA is available at www.giapreza.com. GIAPREZA is marketed by La Jolla Pharmaceutical Company on behalf of La Jolla Pharma, LLC, its wholly owned subsidiary.

IMPORTANT SAFETY INFORMATION

Contraindications

None

Warnings and Precautions

There is a potential for venous and arterial thrombotic and thromboembolic events in patients who receive GIAPREZA. Use concurrent venous thromboembolism (VTE) prophylaxis.

Adverse Reactions

The most common adverse reactions that were reported in greater than 10% of GIAPREZA-treated patients were thromboembolic events.

Drug Interactions

Angiotensin converting enzyme (ACE) inhibitors may increase response to GIAPREZA. Angiotensin II receptor blockers (ARB) may reduce response to GIAPREZA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional information, please see Full Prescribing Information for the United States.

About LJPC-0118

LJPC-0118 is La Jolla’s investigational product for the treatment of severe malaria. The active pharmaceutical ingredient in LJPC-0118, artesunate, was demonstrated to be superior to quinine in reducing mortality in patients with severe falciparum malaria infection in two randomized, controlled, clinical studies. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation and Orphan Drug designation for LJPC-0118 for the treatment of malaria in April 2019 and July 2019, respectively. La Jolla plans to file a New Drug Application (NDA) for LJPC-0118 with the FDA in the fourth quarter of 2019 for the treatment of severe malaria. Severe malaria is a serious and sometimes fatal disease caused by a parasite that

commonly infects a certain type of mosquito, which feeds on humans. Symptoms include but are not limited to: fever, chills, sweating, hypoglycemia and shock. Severe malaria is often complicated by central nervous system infections that may lead to delirium, which may progress to coma. Infections usually occur a few weeks after being bitten. In 2017, an estimated 219 million cases of malaria occurred worldwide, with an estimated 200 million of these cases occurring in the World Health Organization (WHO) African Region, and, in 2013, the global annual incidence of severe malaria was estimated to be 2 million cases. In 2017, an estimated 435,000 people died from malaria worldwide.

About LJPC-401

LJPC-401, a clinical-stage investigational product, is La Jolla’s proprietary formulation of synthetic human hepcidin. Hepcidin, an endogenous peptide hormone, is the body’s naturally occurring regulator of iron absorption and distribution. In healthy individuals, hepcidin prevents excessive iron accumulation in vital organs, such as the liver and heart, where it can cause significant damage and even result in death. La Jolla is developing LJPC-401 for the potential treatment of iron overload, which occurs as a result of primary iron overload diseases such as hereditary hemochromatosis (HH), or secondary iron overload diseases such as beta thalassemia (BT), sickle cell disease (SCD), myelodysplastic syndrome (MDS) and polycythemia vera. The European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has designated LJPC‑401 as an orphan medicinal product for the treatment of beta thalassemia intermedia and major and SCD.

On August 1, 2019 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the second quarter ended June 30, 2019 (Press release, BioMarin, AUG 1, 2019, View Source [SID1234538004]).

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Total Net Product Revenues for the second of quarter 2019 increased to $379.1 million, compared to $367.8 million for the second quarter of 2018. The increase in Net Product Revenues was attributed to the following:

Palynziq Net Product Revenues during the second quarter of 2019 totaled $18.8 million driven primarily by new patients initiating therapy in the U.S. as the product launched in the third quarter of 2018. Palynziq received approval from the U.S. Food and Drug Administration (FDA) in May 2018 and from the European Medicines Agency (EMA) in May 2019. EU commercial sales are expected to commence in the third quarter of 2019; and

Naglazyme Net Product Revenues increased by $7.1 million, or 8%, primarily due to increased sales volume driven by government ordering patterns from certain Latin American and European countries, partially offset by

Aldurazyme Net Product Revenues decreased $18.2 million, due to the timing of customer acceptance for product shipped to Genzyme in the second quarter for which no revenue was recognized as of June 30, 2019. Aldurazyme revenue recognition is based on timing of Genzyme acceptance of product shipment. Approximately $23.0 million of Aldurazyme revenue that was shipped in the second quarter is expected to be recognized in the third quarter of 2019 once product has been accepted by Genzyme. The delay was due to a change in the location where Genzyme receives product. Genzyme’s Aldurazyme revenues, as provided to BioMarin by Genzyme, increased $11.6 million or 9% during the six months ended June 30, 2019, compared to the same period in 2018. Full-year total Aldurazyme revenues are expected to be consistent with full-year Aldurazyme revenues in prior years and in the $100.0 to $120.0 million range; and

Vimizim Net Product Revenues decreased by $4.9 million, or 4%, primarily due to decreased sales volume driven by government ordering patterns in certain Latin American, Middle Eastern and European countries.
The increase in GAAP Net Loss for the second quarter of 2019, compared to the same period in 2018 was primarily due to the following:

higher research and development (R&D) expense related to preclinical activities for our PKU gene therapy development program and clinical activities for our valoctocogene roxaparvovec and vosoritide development programs, offset by decreased R&D expense related to Palynziq for which we began capitalizing manufacturing costs upon FDA approval in May 2018 and a decrease in tralesinidase alfa clinical manufacturing costs. R&D expenses in the quarter were consistent with 2019 guidance despite the acceleration of the valoctocogene roxaparvovec development program and subsequent activities implemented to pursue an expedited regulatory path forward; and

higher intangible asset amortization related to the Palynziq in-process research and development assets that were placed into service following EU approval in May 2019; and

higher selling, general and administrative (SG&A) expense in support of the EU commercial launch and continued U.S. expansion of Palynziq, pre-commercialization activities related to valoctocogene roxaparvovec and increased general and administrative expense primarily attributed to personnel-related costs resulting from increased headcount to support our growth; partially offset by;

increased gross profits of $12.9 million driven by increased product sales.
The increase in GAAP Net Loss for the second quarter of 2019 did not affect the Company’s full-year GAAP Net Loss Guidance, which remains unchanged.
Non-GAAP Income for the second quarter of 2019 decreased $2.8 million, or 14%, to $17.1 million, compared to $19.9 million for the same period in 2018. The decrease in Non-GAAP Income for the quarter, compared to the same period in 2018, was attributed to higher R&D expense and SG&A expense, partially offset by increased gross profit from sales as described above. The decrease in Non-GAAP Income for the second quarter of 2019 did not affect the Company’s full-year Non-GAAP Income Guidance, which remains unchanged.
As of June 30, 2019, BioMarin had cash, cash equivalents and investments totaling approximately $1.1 billion, as compared to $1.3 billion on December 31, 2018.
Commenting on second quarter results, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, "During the first half of 2019 we laid the foundation for a number of significant milestones anticipated over the coming months. We recently announced our plans to submit marketing applications for valoctocogene roxaparvovec gene therapy for severe hemophilia A in both the United States and Europe. We expect to submit both applications in the fourth quarter of this year based on recent interactions with health authorities in those regions. We are pleased

to have the opportunity to initiate the first review of a marketing application for any type of hemophilia indication with a gene therapy product. With valoctocogene roxaparvovec people with severe hemophilia A may soon have the opportunity to experience improved quality of life, including consequences of bleeding, physical functioning, role functioning, emotional impact, treatment concern, and worry. We are very grateful that health authorities are aligned in their focus to expedite the review of this potentially transformative treatment option given the unmet need with current standard of care."
Mr. Bienaimé continued, "Phase 3 results from another potential commercial product, vosoritide for the treatment of achondroplasia, are expected to read-out at the end of this year. Our newest study, a global Phase 2 with vosoritide in infants and young children (less than 60 months old) with achondroplasia is enrolling very well. We expect all subjects ages 6 months through 5 years to be enrolled by year-end. We have been very pleased with the high-level of enthusiasm from families wanting to participate in this program and look forward to starting enrollment in the youngest cohort, infants up to 6 months old, later this year. Another very significant opportunity that is gaining momentum is the global commercialization of Palynziq. We have been very pleased with the pace of the U.S. launch, as we ended the second quarter with 551 patients on reimbursed Palynziq, and an additional 158 naive patients having completed enrollment and awaiting their first injection. Building on this success and as part of our strategy to increase our leadership in the PKU market, we anticipate the submission of an investigational new drug application (IND) and/or a clinical trial application (CTA) for BMN 307, our gene therapy product for PKU, in the second half of 2019. BMN 307 demonstrated lifetime normalization of Phe in a validated PKU mouse model, and as a result, we believe it has the potential to be an important new treatment and market expander as part of our PKU franchise."
2019 Full-Year Financial Guidance unchanged (in millions, except %)

* All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP Income/Loss. Refer to Non-GAAP Information beginning on page 9 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.
Key Program Highlights

Valoctocogene roxaparvovec gene therapy for hemophilia A: On July 8, the Company announced that based on recent meetings with health authorities in the U.S. and Europe, it plans to submit marketing applications to both the FDA and the European Medicines Agency (EMA) in the fourth quarter of 2019 for its investigational gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A.

These submissions will be based on the updated three-year Phase 1/2 data and the recently completed Phase 3 interim analysis of patients treated with valoctocogene roxaparvovec material from the to-be-commercialized process. Both submissions are expected to represent the first time a gene therapy product for any type of hemophilia indication will be reviewed for marketing authorization by health authorities.

The Company has chosen to cease development of the 4e13 vg/kg dose of valoctocogene roxaparvovec given the overwhelming preference by patients to be treated with the 6e13 vg/kg dose. Enrollment continues in the GENEr8-1 Phase 3 study and the 52 week results are anticipated at the end of 2020.

Palynziq for PKU: Palynziq, an injection to reduce blood Phe concentrations in adult patients with PKU, was added to BioMarin’s commercial product portfolio upon its U.S. approval May 2018. As of June 30, 2019, 551 patients were on reimbursed Palynziq, with an additional 158 naïve patients enrolled and awaiting their first treatment with commercial Palynziq. Of the 551 patients on therapy at the end of the second quarter, 410 were formerly naïve patients and 141 transitioned from clinical studies. Of the 125 PKU clinics in the U.S., 92 unique clinics had at least one complete patient enrollment in the REMS program as of June 30, 2019.
On May 6, 2019, the European Commission (EC) granted marketing authorization for Palynziq at doses of up to 60 milligrams once daily, to reduce blood Phe concentrations in patients with PKU aged 16 and older, who have inadequate blood Phe control (blood Phe levels greater than 600 micromol/L) despite prior management with available treatment options. In addition, the EC acknowledged that the Phase 3 trial and extension study is suggestive of an improvement in inattention and mood symptoms.

Vosoritide for children with achondroplasia: On June 18, 2019, the New England Journal of Medicine published the 42 month results from the Phase 2 study with vosoritide in children ages 5 to 14 years. The results also appeared in the July 4 printed issue. BioMarin expects to have over 5 years of clinical data from this Phase 2 study to corroborate maintenance of effect at the time of anticipated marketing application submissions.
The Company expects top line results from the ongoing global, Phase 3 study by year-end 2019. The vosoritide development program includes four distinct areas of focus to support global approval, including a large contemporaneous natural history study which is underway. The global Phase 3 study, which is fully enrolled, is a randomized, placebo-controlled study of vosoritide in approximately 110 children with achondroplasia between the ages of 5 to 14 years.
In 2018, BioMarin began a global Phase 2 study with vosoritide in infants and young children (newborn to 60 months old) with achondroplasia, to determine the impact of treatment in this age group. Three cohorts, segmented by age, are being enrolled in this study. Cohort 1 includes children ages 24 to 60 months old and has completed enrollment. Cohort 2 includes children ages 6 to 24 months old and is expected to complete enrollment by year-end. The Company plans to begin enrolling infants up to 6 months old by year-end.

Tralesinidase alfa (formerly referred to as BMN 250) for MPS IIIB (Sanfilippo Syndrome, Type B): Tralesinidase alfa is currently being evaluated in ongoing natural history and clinical trials. Previously, encouraging signs of biochemical and clinical efficacy have been suggested. Trials are ongoing to collect further data in regard to the untreated natural history of the condition, as well as biochemical and clinical outcomes of therapy.

BMN 307 gene therapy product candidate for phenylketonuria (PKU): As previously announced, the Company expects to submit an IND and/or a CTA for a gene therapy product for the treatment of PKU in the second half of 2019. At R&D Day 2018, BioMarin shared data with BMN 307 that demonstrated a lifetime Phe correction sustained at 80 weeks in preclinical mouse models. BMN 307 is an AAV vector containing the DNA sequence that codes for the phenylalanine hydroxylase enzyme that is deficient in people with PKU. Product to support clinical evaluation will be produced at BioMarin’s gene therapy manufacturing facility, where valoctocogene roxaparvovec is currently made, using a commercial scale manufacturing process to facilitate rapid clinical development.

BMN 290 for Friedreich’s Ataxia: The Company reported plans to cease the preclinical studies in the BMN 290 program based on progress of other portfolio assets that have demonstrated stronger product profiles.
BioMarin will host a conference call and webcast to discuss second quarter 2019 financial results today, Thursday, August 1, 2019 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.
U.S. / Canada Dial-in Number: 866.502.9859
Replay Dial-in Number: 855.859.2056
International Dial-in Number: 574.990.1362
Replay International Dial-in Number: 404.537.3406
Conference ID: 6989536

Conference ID: 6989536

On August 1, 2019 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, reported that the Company will release its second quarter 2019 financial results after the market closes on Thursday, August 8, 2019 (Press release, Synlogic, AUG 1, 2019, View Source [SID1234538020]). The press release will be followed by a conference call at 5:00 pm ET, which will be open to the public via telephone and webcast. During the conference call, the Company will review its financial results and provide a corporate update.

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The conference call dial-in numbers are (844) 815-2882 for domestic callers and (213) 660-0926 for international callers. The conference ID number for the call is 6968273. Participants may access the live webcast via a link on the Synlogic website in the Events Calendar of the Investors and Media section. For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Company’s website.