On October 29, 2020 PellePharm, Inc., a BridgeBio Pharma, Inc. company, reported the presentation of various data highlighting product candidate patidegib topical gel for adults with Gorlin syndrome and high-frequency basal cell carcinoma (HF-BCC) (Press release, PellePharm, OCT 29, 2020, View Source [SID1234569388]). The presentations will be made during the 29th Congress of the European Academy of Dermatology and Venereology (EADV), to be held virtually October 29 – 31, 2020.

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Patidegib topical gel is in development to reduce the large volume of basal cell carcinoma (BCC) tumors that characterize Gorlin syndrome and HF-BCC, at their source, by inhibiting the hedgehog signaling pathway. It is designed to block the SMO signal, thus turning off oncogenic hedgehog activity. Unlike other hedgehog inhibitors, patidegib has been formulated into a topical gel that is stable at room temperature for use as a chronic therapy.

"For rare diseases such as Gorlin syndrome and HF-BCC, with symptoms that manifest on the skin and require treatments that are either invasive or poorly tolerated, we believe that a topical therapeutic designed to both reduce BCC burden and minimize systemic exposure and thereby side effects is ideal for this vulnerable patient population," said Sanuj K. Ravindran, M.D., president and chief executive officer of PellePharm. "Our research continues to generate compelling evidence that supports patidegib as a clinical candidate and validates our approach in hedgehog inhibition."

Details for the poster presentations at EADV Virtual are as follows:

Poster Title: A Phase 1, Single-center, Pharmacokinetic, Safety and Tolerability Study of Patidegib Topical Gel in Healthy Adult Volunteers Under Maximum Use Conditions
Date & Time: Thursday, October 29, 2020, 12:00 p.m. CET
Category: Cutaneous Oncology

Poster Title: A Proof of Concept, Phase 2 Study to Assess Efficacy and Safety of Patidegib for Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Non-Gorlin High-Frequency BCC Patients
Date & Time: Thursday, October 29, 2020, 12:00 p.m. CET
Category: Cutaneous Oncology

Poster Title: A Phase 3 Pivotal Study to Assess Efficacy and Safety of Patidegib for Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas in Patients With Gorlin Syndrome
Date & Time: Thursday, October 29, 2020, 12:00 p.m. CET
Category: Cutaneous Oncology

Poster Title: Gorlin Syndrome: It’s the Pits*
Date & Time: Thursday, October 29, 2020, 12:00 p.m. CET
Category: Cutaneous Oncology
*This poster is presented by Julie Breneiser on behalf of GSA (Gorlin Syndrome Alliance).

"We are encouraged by the continuing promise that patidegib is demonstrating in the clinic. A topical formulation has the potential to bring significant benefit to the Gorlin Syndrome patient and for patients with HF-BCC, helping manage the burden of the diseases with convenient self-administration at home," said Patrice Baudry, vice president of rare disease at LEO Pharma.

In November 2018, PellePharm and LEO Pharma entered into a strategic collaboration to address the unmet medical needs for rare skin conditions, such as Gorlin syndrome and HF-BCC. LEO Pharma is providing resources to PellePharm to fund, among other activities, its Phase 3 trial of patidegib topical gel 2% in patients with Gorlin syndrome under the terms of the agreement.

About Patidegib

Patidegib topical gel, an investigational treatment, is designed to reduce the basal cell carcinoma (BCC) tumor burden in people living with Gorlin syndrome and high frequency BCC (HF-BCC) by blocking the disease at its source within the hedgehog signaling pathway. Patidegib topical gel has shown early promise in a Phase 2 clinical study for the mitigation of BCC tumors in Gorlin syndrome. The topical formulation of patidegib was developed with a goal of providing the clinical activity previously demonstrated by oral Patidegib in Phase 1 trials and a favorable tolerability profile without the adverse systemic side effects observed with the oral class of hedgehog inhibitors. The topical gel formulation is stable at room temperature for at least two years, potentially making it an option for ongoing, at-home management of Gorlin syndrome and HF-BCC. PellePharm has received both Orphan Drug Designation and Breakthrough Therapy Designation for Patidegib Topical Gel in Gorlin Syndrome from the FDA, as well as Orphan Drug Designation in Gorlin Syndrome from EMA’s Committee for Orphan Medicinal Products in the EU.

About Gorlin Syndrome

Gorlin syndrome is a rare, genetic disease characterized by constitutional, heritable mutations in one allele of the tumor suppressor gene encoding PATCHED1 (PTCH1), which acts as the primary inhibitor of the hedgehog signaling pathway. This leads to the formation of multiple basal cell carcinomas (BCCs), often on the face.

With no FDA-approved drugs available for people living with Gorlin syndrome, the standard of care for treating BCCs is surgery. People with severe Gorlin syndrome may have as many as 30 surgeries per year, which can be repetitive, scarring and disfiguring. Approximately 10,000 people in the United States, or one in 31,000, are believed to be affected by Gorlin syndrome. Gorlin syndrome is known by several names, including Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS) and Nevoid Basal Cell Carcinoma Syndrome (NBCCS).

About High Frequency Basal Cell Carcinoma (HF-BCC)

HF-BCC, like Gorlin syndrome, is a rare disease which is characterized by the development of an abnormally high number of basal cell carcinomas (BCCs). Unlike people with Gorlin syndrome, people with HF-BCC are not born with a germline PTCH1 mutation and do not suffer from the other systemic manifestations of Gorlin syndrome. The current standard of care for people living with HF-BCC is BCC surgery.

On October 29, 2020 Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported financial results and provided business updates for the third quarter of 2020 and highlighted pipeline progress (Press release, Moderna Therapeutics, OCT 29, 2020, View Source [SID1234569387]).

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"The Moderna team continued to execute on our plan in the third quarter. We now have four programs in Phase 2 studies, in addition to the Phase 3 study of our COVID-19 vaccine, mRNA-1273, which is fully enrolled. Our CMV vaccine showed positive interim Phase 2 data and we are now preparing for the Phase 3 start in 2021. We are actively preparing for the launch of mRNA-1273 and we have signed a number of supply agreements with governments around the world. Moderna is committed to the highest data quality standards and rigorous scientific research as we continue to work with regulators to advance mRNA-1273," said Stéphane Bancel, Chief Executive Officer of Moderna. "I believe that if we launch our COVID-19 vaccine, 2021 could be the most important inflection year in Moderna’s history. We will have the resources to scale Moderna to maximize the impact we can have on patients in the next 10 years through numerous new medicines."

New updates and recent progress include:

Infectious Diseases

Phase 3 COVE study of COVID-19 vaccine candidate (mRNA-1273) conducted in collaboration with NIH and BARDA fully enrolled with 30,000 participants, including 37% from diverse communities
Positive interim data from Phase 2 study of CMV vaccine candidate (mRNA-1647) announced during R&D Day on September 17; Moderna preparing for pivotal Phase 3 study expected to begin in 2021
First cohort of Phase 1 study of RSV vaccine candidate (mRNA-1345) fully enrolled
Resumed dosing pediatric participants in Phase 1b age de-escalation study of hMPV/PIV3 vaccine candidate (mRNA-1653) following COVID-19 disruptions
Oncology

First patients dosed in Phase 2 dose expansion study of OX40L (mRNA-2416) in combination with durvalumab for ovarian cancer
Rare Diseases

Rare pediatric disease designation received for next generation MMA candidate (mRNA-3705)
Study start-up activities for Phase 1/2 study of PA candidate (mRNA-3927) have resumed following COVID-19 related pause and protocol amendment
Moderna currently has 21 mRNA development candidates in its portfolio with 13 in clinical studies. Across Moderna’s pipeline, more than 32,000 healthy volunteers and patients have been enrolled in clinical studies, including the Phase 3 study of mRNA-1273. The Company’s updated pipeline can be found at www.modernatx.com/pipeline. Moderna and collaborators have published more than 55 peer-reviewed papers.

Summary of Program Highlights by Modality

Core Modalities

Prophylactic Vaccines: Moderna is developing vaccines against viral diseases where there is unmet medical need – including complex vaccines with multiple antigens for common diseases, as well as vaccines against threats to global public health. The Company’s global public health portfolio is focused on epidemic and pandemic diseases for which funding has been sought from governments and non-profit organizations.

Infections transmitted from mother to baby

Cytomegalovirus (CMV) vaccine (mRNA-1647): Positive interim data from the Phase 2 study assessing the safety, reactogenicity, and immunogenicity of different dose levels of mRNA-1647 were presented at Moderna’s annual R&D Day. Based on the interim analysis of the Phase 2 study, the 100 μg dose has been chosen for the Phase 3 pivotal study, which is expected to begin in 2021. Moderna owns worldwide commercial rights for mRNA-1647.
Zika virus vaccine (mRNA-1893): All dose cohorts (10, 30, 100 and 250 µg) in the Phase 1 study of mRNA-1893 have completed enrollment. Moderna is preparing for a Phase 2 study of mRNA-1893. mRNA-1893 is being developed in collaboration with the U.S. Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services. Moderna owns worldwide commercial rights to mRNA-1893.
Vaccines against respiratory infections

COVID-19 vaccine (mRNA-1273): On October 22, the Phase 3 COVE study of COVID vaccine candidate (mRNA-1273) being conducted with NIH and BARDA completed enrollment with approximately 37% of participants from diverse communities; 25% were older (>65 years) and 17% had co-morbid risk factors. The Phase 1 interim analysis, published in The New England Journal of Medicine on July 14, showed that mRNA-1273 was generally well-tolerated across all age groups and induced rapid and strong immune responses against SARS-CoV-2. In the 18-55 age group, neutralizing antibody titers were observed in 100% of evaluated participants and at the 100 µg dose level selected for Phase 3, the geometric mean titers were above those seen in convalescent sera. Similarly, the second interim analysis of mRNA-1273, published in The New England Journal of Medicine on September 29, showed that mRNA-1273 induced consistently high levels of neutralizing antibody titers in all participants in the 56-70 and 71+ age groups. In addition, vaccination with mRNA-1273 elicited Th1-biased CD4 T cell responses in all age groups. The ongoing Phase 3 COVE study is a case-driven analysis with two planned interim analyses. At the first interim analysis, three potential outcomes include: the study meets the statistical hurdle (>74%) and the Company will be unblinded and will evaluate whether to proceed with a regulatory submission; the study does not meet the statistical hurdle and the study continues; or the study is determined to be futile. Moderna is committed to full transparency and will share the outcome of each interim analysis. BARDA, part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), partially supported the research and development of mRNA-1273 with federal funding under Contract no. 75A50120C00034. A summary of the Company’s work to date on COVID-19 can be found here. Moderna retains worldwide rights to develop and commercialize mRNA-1273.
Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): Sites have resumed dosing seropositive pediatric participants (12-36 months of age) in the Phase 1 study of hMPV/PIV3 study (mRNA-1653) following the COVID-19 related study disruption. Moderna owns worldwide commercial rights to mRNA-1653.
Pediatric respiratory syncytial virus (RSV) vaccine (mRNA-1345): The first cohort of the Phase 1 study of mRNA-1345 is fully enrolled. This Phase 1 study includes initial dosing in adults, followed by age de-escalation into children. mRNA-1345 is a vaccine against RSV in young children encoding for a prefusion F glycoprotein, which elicits a superior neutralizing antibody response compared to the postfusion state. The Company intends to combine mRNA-1345 with mRNA-1653, its vaccine against hMPV and PIV3, to create a combination vaccine against RSV, hMPV and PIV3. There is no approved vaccine for RSV. Moderna owns worldwide commercial rights to mRNA-1345.
Seasonal influenza (flu): At Moderna’s annual R&D Day, the Company announced that it is entering the seasonal flu business. Seasonal flu (type A and type B) epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing substantial burden on healthcare systems. Currently approved vaccines are 40-60% effective and face significant challenges from strain mismatch1; high-risk groups would benefit from higher efficacy, which the Company believes its mRNA platform may be capable of delivering.
Pandemic influenza/H7N9 vaccine (mRNA-1851): Discussions regarding funding the Company’s pandemic influenza/H7N9 vaccine program through approval are ongoing.
Vaccines against highly prevalent viral infections

Epstein-Barr virus (EBV) vaccine (mRNA-1189): mRNA-1189 is a vaccine against EBV containing five mRNAs that encode viral proteins (gp350, gB, gp42, gH and gL) in EBV. Similar to Moderna’s CMV vaccine (mRNA-1647), the viral proteins in mRNA-1189 are expressed in their native membrane-bound form for recognition by the immune system. There is no approved vaccine for EBV. Moderna owns worldwide commercial rights to mRNA-1189.
Systemic Secreted & Cell Surface Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are either secreted or expressed on the cell surface.

Antibody against the chikungunya virus (mRNA-1944): Positive interim data from the Phase 1 study evaluating escalating doses of mRNA-1944 in the 0.6 mg/kg dose with steroid premedication cohort and two doses of 0.3 mg/kg (without steroid premedication) given one week apart cohort were presented at Moderna’s annual R&D Day and demonstrated dose-dependent increases in levels of antibody against chikungunya. Safety and increased CHKV-IgG production in the two-dose regimen shows the platform’s ability for repeat dosing.
IL-2 (mRNA-6231): mRNA-6231 is an mRNA encoding for a long-acting tolerizing IL-2. This new autoimmune development candidate is designed to preferentially activate and expand the regulatory T cell population. The Company plans to conduct a Phase 1 study of mRNA-6231 in healthy adult volunteers. mRNA-6231 uses the same LNP formulation as mRNA-1944. The Phase 1 study of mRNA-6231 will be the first clinical demonstration of subcutaneous administration of this delivery technology. Moderna owns worldwide commercial rights to mRNA-6231.
PD-L1 (mRNA-6981): mRNA-6981 is an mRNA encoding for PD-L1. This new autoimmune development candidate is designed to augment cell surface expression of PD-L1 on myeloid cells to provide co-inhibitory signals to self-reactive lymphocytes. As an initial step to addressing a range of autoimmune indications, the Company intends to pursue proof-of-concept in a Phase 1 study of mRNA-6981 in type 1 autoimmune hepatitis (AIH), a condition that involves liver inflammation and can lead to cirrhosis and liver failure. mRNA-6981 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-6981.
Relaxin (AZD7970): Partnered with AstraZeneca, AZD7970 is in preclinical development for the treatment of heart failure. Under the terms of the collaboration, AstraZeneca would sponsor the Phase 1 trial to assess safety, tolerability and duration of systemic exposure to the Relaxin protein. Moderna shares worldwide commercial rights to AZD7970 with AstraZeneca.
Exploratory Modalities

Cancer Vaccines: These programs focus on stimulating a patient’s immune system with antigens derived from tumor-specific mutations to enable the immune system to elicit a more effective anti-tumor response.

Personalized cancer vaccine (PCV) (mRNA-4157): The randomized Phase 2 study investigating a 1 mg dose of mRNA-4157 in combination with Merck’s pembrolizumab (KEYTRUDA), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma is ongoing. The Phase 1 study is ongoing. Moderna shares worldwide commercial rights to mRNA-4157 with Merck.
Mutant KRAS vaccine (mRNA-5671 or V941): The Phase 1 open-label, multi-center study to evaluate the safety and tolerability of mRNA-5671 both as a monotherapy and in combination with pembrolizumab, led by Merck, is ongoing. Moderna shares worldwide commercial rights to mRNA-5671 with Merck.
Intratumoral Immuno-Oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): The Phase 1/2 study of mRNA-2416 alone and in combination with durvalumab (IMFINZI) is ongoing. The Phase 2 dose expansion study of mRNA-2416 in combination with durvalumab in ovarian cancer patients is enrolling and the first patients have been dosed. Moderna owns worldwide commercial rights to mRNA-2416.
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752): The Phase 1 trial evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with advanced solid tumor malignancies and lymphoma is ongoing. mRNA-2752 is an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators. Moderna owns worldwide commercial rights to mRNA-2752.
IL-12 (MEDI1191): The Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with durvalumab in patients with advanced solid tumors, led by AstraZeneca, is ongoing. MEDI1191 is an mRNA encoding for IL-12, a potent immunomodulatory cytokine. Moderna shares worldwide commercial rights to MEDI1191 with AstraZeneca.
Localized Regenerative Therapeutics: Localized production of proteins has the potential to be used as a regenerative medicine for damaged tissues.

VEGF-A (AZD8601): The Phase 2a study of AZD8601 VEGF-A, which is being developed for patients with ischemic heart disease undergoing coronary artery bypass grafting (CABG) surgery with moderately impaired systolic function, led by AstraZeneca, is ongoing. Moderna has licensed worldwide commercial rights to AZD8601 to AstraZeneca.
Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Methylmalonic acidemia (MMA) (mRNA-3705): Moderna received rare pediatric designation for its next generation MMA candidate (mRNA-3705). The Company plans to file new IND and CTA applications for mRNA-3705 and will focus development efforts on that candidate going forward. mRNA-3705 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-3705.
Propionic acidemia (PA) (mRNA-3927): Study start-up activities for the Phase 1/2 study of PA candidate (mRNA-3927) have resumed following COVID-19 related pause and protocol amendment. mRNA-3927 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-3927.
Publication of Note: Publication in Nature shows mRNA therapy (mRNA-3927) restores functional PCC enzyme and metabolic function in long term repeat dose studies in mice.
MMA and PA Natural History Study (MaP): This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to MUT deficiency or PA and is designed to identify and correlate clinical and biomarker endpoints for these disorders. Enrollment in the study has been completed.
Phenylketonuria (PKU) (mRNA-3283): Individuals with PKU have a deficiency in phenylalanine hydroxylase (PAH) resulting in a reduced or complete inability to metabolize the essential amino acid phenylalanine into tyrosine. mRNA-3283 encodes human PAH to restore the deficient or defective intracellular enzyme activity in patients with PKU. mRNA-3283 is in preclinical development. Moderna owns worldwide commercial rights to mRNA-3283.
Glycogen storage disease type 1a (GSD1a) (mRNA-3745): Individuals with GSD1a have a deficiency in glucose-6-phosphatase resulting in pathological blood glucose imbalance. mRNA-3745 is an IV-administered mRNA encoding human G6Pase enzyme, designed to restore the deficient or defective intracellular enzyme activity in patients with GSD1a. mRNA-3745 is in preclinical development. Moderna owns worldwide commercial rights to mRNA-3745.
Information about each development candidate in Moderna’s pipeline, including those discussed in this press release, can be found on the investor relations page of its website: investors.modernatx.com.

Research Updates

New collaboration with Vertex to treat cystic fibrosis using gene editing: On September 16, Moderna and Vertex announced a new strategic research collaboration and licensing agreement aimed at the discovery and development of therapeutics that leverage Moderna’s lipid nanoparticles (LNPs) and mRNA platform to deliver gene-editing therapies for the treatment of cystic fibrosis. The three-year research collaboration initially will focus on the discovery and optimization of novel LNPs and mRNAs that can deliver gene-editing therapies to cells in the lungs, enabling functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to be produced.
Collaboration with Chiesi Group for mRNA therapeutics to treat pulmonary arterial hypertension (PAH): On September 16, Moderna and Chiesi Group announced a mRNA therapeutics for the treatment of pulmonary arterial hypertension (PAH), a rare disease with an incidence of 2-5 per million adults2.
New award from DARPA: On October 8, the Defense Advanced Research Projects Agency (DARPA) awarded Moderna up to $56 million to enable small-scale, rapid mobile manufacturing of nucleic acid vaccines and therapeutics as part of DARPA’s Nucleic Acids On-Demand World-Wide (NOW) initiative to develop a medical countermeasure manufacturing platform.
Management Updates

Moderna’s General Counsel and Corporate Secretary, Lori Henderson, J.D., has announced her decision to retire in 2021. Moderna will begin the search for a new General Counsel as the Company continues on the path toward commercialization. Lori will remain with Moderna well into 2021 to ensure a smooth transition with Moderna’s next General Counsel.
"I would like to thank Lori for her significant contributions during her time at Moderna, including helping us transition Moderna from a private to a public company and building a legal team to support the company during its rapid growth and expansion. She has been a great partner and champion of our people and our mission for patients. On behalf of Moderna, I thank Lori for her continued leadership and wish her all the best on her new life in retirement," said Stéphane Bancel.

John Lepore joined Moderna as Senior Vice President, Government Engagement on August 10.
Moderna named Michael Mullette Vice President, North America Commercial Operations on September 10.
COVID-19 Vaccine Supply Agreements & Regulatory Filings

North America: On August 11, Moderna announced a supply agreement with the U.S. government for an initial 100 million doses of mRNA-1273. On September 22, Canada exercised an increased option for 20 million doses of mRNA-1273. On October 13, Moderna announced the initiation of a rolling submission to Health Canada for mRNA-1273.
Europe: On August 24, Moderna confirmed advanced discussions with the European Commission to supply Europe with 80 million doses of mRNA-1273. On October 14, Moderna received confirmation of eligibility for submission of Marketing Authorization Application to the European Medicines Agency for mRNA-1273. On September 16, Moderna announced its first commercial organization outside of North America in Switzerland. Additionally, the Swiss Federal Government concluded an agreement with the Company for the procurement of 4.5 million doses of mRNA-1273. On October 27, the Company announced that the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom started the rolling review process of mRNA-1273.
Asia-Pacific: On October 29, Moderna confirmed that the Ministry of Health, Labour and Welfare of Japan and Takeda Pharmaceutical Co., Ltd (NYSE: TAK) have agreed to purchase and distribute 50 million doses of mRNA-1273.
Middle East: On June 17, the government of Israel confirmed a supply agreement with Moderna for mRNA-1273. On October 25, Moderna announced a supply agreement with the Ministry of Public Health of Qatar for mRNA-1273.
COVAX: Discussions are ongoing with COVAX on a tiered pricing proposal for purchasing mRNA-1273.
Corporate Update

On September 17, Moderna hosted its annual R&D Day
2020 Financial Update

Moderna updates 2020 outlook, and now expects positive net cash provided by operating activities and used for purchases of property and equipment to be between $0.1 billion and $0.3 billion, driven by customer deposits of approximately $1.2 billion received year-to-date as of September 30, 2020.
The Company expects net cash provided by operating activities and purchases of property and equipment in 2020 to continue to evolve as it receives additional customer deposits.
Third Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and investments as of September 30, 2020 and December 31, 2019 were $3.97 billion and $1.26 billion, respectively.
Net Cash Provided by Operating Activities: Net cash provided by operating activities was $762.7 million for the nine months ended September 30, 2020 compared to $(359.9 million) used in operating activities for the same period in 2019. Net cash provided by operating activities increased significantly in 2020 mainly due to an increase in deferred revenue attributable to deposits of $1.17 billion received based on the supply agreements with the U.S. Government and several international government agencies for our future mRNA-1273 vaccine supply.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $44.1 million for the nine months ended September 30, 2020 compared to $24.9 million for the same period in 2019.
Revenue: Total revenue was $157.9 million for the three months ended September 30, 2020 compared to $17.0 million for the same period in 2019. Total revenue was $232.7 million for the nine months ended September 30, 2020 compared to $46.2 million for the same period in 2019. Total revenue increased for both the three month and nine month periods in 2020, due to increases in grant revenue, primarily due to our BARDA agreement related to our mRNA-1273 vaccine candidate development.
Research and Development Expenses: Research and development expenses were $344.5 million for the three months ended September 30, 2020 compared to $119.6 million for the same period in 2019. Research and development expenses were $611.5 million for the nine months ended September 30, 2020 compared to $378.4 million for the same period in 2019. The increases for both the three month and nine month periods in 2020 were mainly due to increases in clinical trial expenses, an increase in raw materials and manufacturing costs, an increase in personnel related costs, and an increase in consulting and outside services, largely driven by increased headcount and mRNA-1273 clinical development.
General and Administrative Expenses: General and administrative expenses were $48.5 million for the three months ended September 30, 2020 compared to $28.2 million for the same period in 2019. General and administrative expenses were $109.3 million for the nine months ended September 30, 2020 compared to $83.9 million for the same period in 2019. The increases were mainly due to an increase in personnel related costs, an increase in legal related costs, and an increase in consulting and outside services. The increases were primarily attributable to increased headcount and mRNA-1273 vaccine candidate development and commercialization activities.
Net Loss: Net loss was $233.6 million for the three months ended September 30, 2020 compared to $123.2 million for the same period in 2019. Net loss was $474.6 million for the nine months ended September 30, 2020 compared to $390.7 million for the same period in 2019.
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Thursday, October 29, 2020. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 1938847. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for one year following the presentation.

On October 29, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported that the company will deliver two poster presentations at The American Society of Dermatopathology (ASDP) 57th Virtual Annual Meeting, to be held on Nov. 5 – 11, 2020 (Press release, Castle Biosciences, OCT 29, 2020, View Source [SID1234569386]).

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Presentation details are as follows:

DecisionDx-Melanoma
Poster #: 592
Title: Identifying predictors of sentinel lymph node metastasis in cutaneous melanoma patients using molecular and clinicopathologic high-risk features
Session: Oral & Poster Abstract Defense 2
Presenter: Federico Monzon, M.D.
Date: Tuesday, November 10, 2020
Time: 11:30 a.m. – 12:30 p.m. Central time

DecisionDx DiffDx-Melanoma
Poster #: 296
Title: Development and validation of a diagnostic gene expression profile test for ambiguous or difficult to diagnose pigmented skin lesions
Session: Oral & Poster Abstract Defense 1
Presenter: Sarah Estrada, M.D., FCAP
Date: Monday, November 9, 2020
Time: 11:00 a.m. – 12:00 p.m. Central time

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included more than 3,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through June 30, 2020, DecisionDx-Melanoma has been ordered more than 59,900 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.SkinMelanoma.com.

About Suspicious Pigmented Lesions

In the U.S., approximately 2 million skin biopsies of pigmented or melanocytic lesions are performed annually, which Castle estimates leads to the diagnosis of 130,000 invasive melanoma cases and more than 96,000 in situ melanoma cases. These biopsies are typically pigmented lesions for which the healthcare provider suspects melanoma. The majority of these biopsies receive a definitive diagnosis by the dermatopathologist using traditional microscopic analyses. However, approximately 300,000 of these biopsies are considered difficult-to-diagnose using this traditional method and require additional testing to clarify the likelihood that this lesion is benign or malignant. And though there are several options for further testing, Castle believes there is a need for improvements in objective tests to resolve this diagnostic dilemma.

On October 29, 2020 Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies, reported a collaboration with AstraZeneca (LSE/STO/Nasdaq: AZN) to evaluate domvanalimab (AB154), Arcus’s investigational anti-TIGIT antibody, in combination with Imfinzi (durvalumab) in a registrational Phase 3 clinical trial in patients with unresectable Stage III non-small cell lung cancer (NSCLC) (Press release, Arcus Biosciences, OCT 29, 2020, View Source [SID1234569385]). Imfinzi is the only immunotherapy approved for patients with unresectable Stage III NSCLC and was the first significant advancement in over twenty-five years for the treatment of patients with Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT). The collaboration reflects Arcus’s commitment to ensuring the development of its portfolio of molecules in combinations and settings that maximize their value and bring their potential benefits to the broadest patient population possible.

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"This collaboration provides a unique opportunity for domvanalimab, our novel anti-TIGIT antibody, to be combined with the definitive standard of care in the curative-intent setting of unresectable Stage III NSCLC and to leverage AstraZeneca’s experience, deep knowledge and leadership within this indication," said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. "With the aggressive development of our anti-TIGIT antibody in this additional setting, we are well positioned to be a leader in both the anti-TIGIT field and more broadly in the creation, development and commercialization of the next generation of innovative immuno-oncology combination therapies."

José Baselga, M.D., Ph.D., Executive Vice President, Oncology R&D of AstraZeneca, said: "This partnership creates an important opportunity to leverage the promise of Arcus’s anti-TIGIT antibody in Stage III NSCLC. This is a promising immunotherapy combination that has the potential to further enhance the efficacy and improvement of long-term survival that Imfinzi has already demonstrated in this setting, and to allow us to unlock the full potential of this medicine."

Results from the PACIFIC Phase 3 trial recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting demonstrated that treatment with Imfinzi following CRT led to unprecedented survival in unresectable Stage III NSCLC, with an estimated 50% of patients surviving four years versus 36% for CRT alone, and 35% of patients not progressing after four years versus 20% for CRT alone. These data build on those reported in 2018 in The New England Journal of Medicine, demonstrating a significant benefit associated with Imfinzi treatment in the overall survival primary endpoint.

Arcus is currently evaluating domvanalimab, a new potential immuno-oncology backbone therapy in a three-arm randomized Phase 2 study, ARC-7, for first-line treatment of PD-L1-high metastatic NSCLC evaluating (1) zimberelimab monotherapy, versus (2) domvanalimab with zimberelimab versus (3) domvanalimab plus etrumadenant (AB928) with zimberelimab.

Under the terms of the agreement, each company will retain existing rights to their respective molecules and any future commercial economics. AstraZeneca will conduct the trial, and each company will supply its respective anti-cancer agent to support the trial. Pursuant to the terms of the agreement, the parties will share costs for the trial.

Consistent with the terms of the recently completed Arcus-Gilead partnership, Gilead maintains an option to co-develop and co-commercialize domvanalimab. If Gilead exercises its option to domvanalimab, the trial from this AstraZeneca collaboration is expected to form part of the Arcus and Gilead joint development program and Arcus’s portion of the trial costs would be shared with Gilead. The collaboration with AstraZeneca has the potential to expand domvanalimab’s clinical development program, accelerating the pathway to registration and adding value to the Arcus-Gilead alliance.

On October 29, 2020 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported financial results for the third quarter of 2020 (Press release, Alexion, OCT 29, 2020, View Source [SID1234569384]). Total revenues in the third quarter were $1,588.7 million, a 26 percent increase compared to the same period in 2019. The negative impact of foreign currency on total revenues year-over-year was 2 percent, or $25.5 million, inclusive of hedging activities. On a GAAP basis, diluted EPS in the quarter was $2.62, compared to $2.08 in the prior year. Non-GAAP diluted EPS for the third quarter of 2020 was $3.24, a 16 percent increase versus the third quarter of 2019.

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"We have continued to build on our momentum from the first half of the year, delivering another strong quarter despite the ongoing challenges and uncertainty surrounding COVID-19. In the third quarter, we further progressed our LEAD-EXPAND-DIVERSIFY strategy with multiple regulatory approvals, the initiation of new Phase 3 trials and the integration of the Portola team," said Ludwig Hantson, Ph.D., Chief Executive Officer of Alexion. "Our foundation for the future is stronger than ever, and by maintaining our focus on serving patients and delivering for shareholders, I am confident that we will continue to build on our success to date and further advance our mission of delivering life-changing therapies to people with rare diseases and devastating conditions."

Third Quarter 2020 Financial Highlights

Net product sales were $1,588.3 million in the third quarter of 2020, compared to $1,263.1 million in the third quarter of 2019.
SOLIRIS net product sales were $1,042.3 million, compared to $990.5 million in the third quarter of 2019, representing a 5 percent increase.
ULTOMIRIS net product sales were $289.3 million, compared to $89.9 million in the third quarter of 2019, representing a 222 percent increase.
STRENSIQ net product sales were $189.4 million, compared to $154.3 million in the third quarter of 2019, representing a 23 percent increase.
KANUMA net product sales were $28.4 million in both of the third quarters of 2020 and 2019.
ANDEXXA/ONDEXXYA net product sales were $38.9 million in the third quarter of 2020.
GAAP cost of sales was $144.7 million, compared to $95.2 million in the third quarter of 2019. Non-GAAP cost of sales was $129.8 million, compared to $91.8 million in the third quarter of 2019.
GAAP R&D expense was $285.9 million, compared to $232.9 million in the third quarter of 2019. Non-GAAP R&D expense was $269.3 million, compared to $186.1 million in the third quarter of 2019.
GAAP SG&A expense was $334.2 million, compared to $299.3 million in the third quarter of 2019. Non-GAAP SG&A expense was $301.3 million, compared to $260.4 million in the third quarter of 2019.
GAAP income tax expense was $88.8 million, compared to $67.9 million in the third quarter of 2019. Non-GAAP income tax expense was $135.1 million, compared to $82.5 million in the third quarter of 2019.
GAAP diluted EPS was $2.62, compared to $2.08 in the third quarter of 2019. Non-GAAP diluted EPS was $3.24, compared to $2.79 in the third quarter of 2019.
COVID-19

We continue to take steps to proactively respond to the evolving COVID-19 pandemic and to plan for related uncertainties. We remain focused on continuing to serve patients, protecting the health and safety of our employees and the communities in which we live and work, and supporting patients in clinical trials. We are also focused on minimizing potential interactions that could contribute to the spread of the virus and put additional strain on healthcare systems through the use of innovative virtual means where possible.

Clinical Trials: We have implemented a pandemic response business continuity plan designed to protect patients and site staff safety while continuing our clinical trials with limited interruption to the extent we are able. The COVID-19 impact has varied by study and program, but there has been little timing impact on fully-enrolled trials. We have successfully re-initiated the majority of studies that had been temporarily paused. There has been, and may continue to be, an impact to the timing of trials that are enrolling patients and activating sites, or have not yet started to do so, based on local dynamics where these studies are being conducted.
Business Impact: We continue to take proactive measures designed to mitigate the risk of potential interruptions in supply and/or access to patients’ customary site-of-care locations. Treatment compliance rates across all our medicines have remained strong and continue to be slightly above expectations. We have also seen the predicted slowing of new patient initiations and delays in treatment starts, and we are continuing to closely monitor this environment as the pandemic continues.
Research and Development

PHASE 3/4

SOLIRIS – Neuromyelitis Optica Spectrum Disorder (NMOSD): A Phase 2/3 study of SOLIRIS in children and adolescents with NMOSD is underway.
SOLIRIS – Generalized Myasthenia Gravis (gMG): A Phase 3 study of SOLIRIS in children and adolescents with gMG is underway.
SOLIRIS – Guillain-Barre Syndrome (GBS): SOLIRIS in GBS has been granted SAKIGAKE designation by Japan’s Ministry of Health, Labour and Welfare (MHLW). Alexion plans to initiate a Phase 3 study of SOLIRIS in GBS in Japan in 2021, pending regulatory feedback.
ULTOMIRIS – Severe COVID-19: A Phase 3 randomized controlled trial of ULTOMIRIS in adults with COVID-19 who are hospitalized with severe pneumonia or acute respiratory distress syndrome is underway.
ULTOMIRIS – Paroxysmal Nocturnal Hemoglobinuria (PNH): A Phase 3 study of ULTOMIRIS in children and adolescents with PNH is underway.
ULTOMIRIS – Atypical Hemolytic Uremic Syndrome (aHUS): In September 2020, Japan’s MHLW approved ULTOMIRIS for adults and children with aHUS. A global Phase 3 study of ULTOMIRIS in children and adolescents with aHUS is underway.
ULTOMIRIS – 100 mg/mL: In October 2020, the U.S. FDA approved the ULTOMIRIS 100 mg/mL formulation for PNH and aHUS. In September 2020, Alexion announced a positive opinion for the ULTOMIRIS 100 mg/mL formulation from the European Medicines Agency Committee for Medicinal Products for Human Use. An application for approval is under review in Japan. This higher concentration formulation is designed to reduce infusion time by more than 60 percent to approximately 45 minutes.
ULTOMIRIS – Subcutaneous: The Phase 3 study of weekly subcutaneous (SC) ULTOMIRIS demonstrated PK-based non-inferiority versus intravenous ULTOMIRIS. Pending collection of 12-month safety and drug-device combination data, Alexion plans to file for approval in the U.S. and EU for the ULTOMIRIS SC formulation and device combination in PNH and aHUS in the third quarter of 2021.
ULTOMIRIS – gMG: As completion of full enrollment nears, screening of new patients has closed for the Phase 3 study of ULTOMIRIS in adults with gMG.
ULTOMIRIS – NMOSD: A Phase 3 study of ULTOMIRIS in NMOSD is underway.
ULTOMIRIS – Amyotrophic Lateral Sclerosis (ALS): A Phase 3 study of ULTOMIRIS in ALS is underway.
ULTOMIRIS – Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA): Alexion has initiated a Phase 3 study of ULTOMIRIS in adults with HSCT-TMA and plans to initiate a Phase 3 study in children with HSCT-TMA by the end of 2020.
ULTOMIRIS – Complement Mediated Thrombotic Microangiopathy (CM-TMA): Alexion plans to initiate a Phase 3 study of ULTOMIRIS in CM-TMA in the first half of 2021, pending regulatory feedback.
ALXN1840 – Wilson Disease: Enrollment is complete in a Phase 3 study of ALXN1840 in Wilson disease. Study results are expected in the first half of 2021.
CAEL-101 – Caelum Biosciences: In September 2020, Alexion and Caelum Biosciences announced the initiation of the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101, a first-in-class amyloid fibril targeted therapy, in combination with standard-of-care therapy in AL amyloidosis. Enrollment is underway in two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease.
ALXN2060 (AG10) – Eidos: Alexion holds an exclusive license to develop and commercialize ALXN2060 (AG10) in Japan. Eidos is currently evaluating AG10 in a Phase 3 study in the U.S. and Europe for ATTR cardiomyopathy (ATTR-CM) and plans to begin a Phase 3 study in ATTR polyneuropathy (ATTR-PN) in the second half of 2020. Alexion plans to initiate a Phase 3 bridging study of ALXN2060 for patients with ATTR-CM in Japan by the end of 2020.
ALXN2040 (Danicopan) – PNH with Extravascular Hemolysis (EVH): Alexion plans to initiate a Phase 3 study of ALXN2040 as an add-on therapy for PNH patients with EVH by the end of 2020.
ANDEXXA – Acute Intracranial Hemorrhage (ICH): The Phase 4 ANNEXA-I study – designed to provide clinical data supporting full approval – is underway to assess ANDEXXA compared to usual standard of care in patients presenting with acute intracranial hemorrhage while taking an oral Factor Xa inhibitor.
PHASE 1/2

ULTOMIRIS – Renal Diseases: Alexion plans to initiate a proof-of-concept trial of ULTOMIRIS in patients with IgA nephropathy and lupus nephritis in 2020.
ALXN1830: Due to COVID-19, Alexion discontinued the Phase 2 study of ALXN1830, administered intravenously, in warm autoimmune hemolytic anemia (WAIHA) and paused the Phase 1 study of a subcutaneous formulation of ALXN1830 in healthy volunteers. The paused Phase 1 study and new Phase 2 studies of subcutaneous ALXN1830 in gMG and WAIHA are planned to begin in 2021.
ALXN2040 – Geographic Atrophy (GA): Alexion plans to initiate a Phase 2 study of ALXN2040 in GA in the second half of 2021.
ALXN2050 – PNH: A Phase 2 study of ALXN2050 monotherapy in PNH is underway.
ALXN2050 – Renal Diseases: Alexion plans to initiate a proof-of-concept trial of ALXN2050 in patients with various renal diseases in 2021, pending regulatory feedback.
ALXN1720: Seven of nine cohorts are complete in a Phase 1 healthy volunteer study of ALXN1720, a novel anti-C5 albumin-binding bi-specific mini-body that is designed to bind and prevent activation of human C5. Remaining cohorts of the study, which had previously been paused due to COVID-19, have been restarted. Data are expected in the first half of 2021. Following successful completion of the Phase 1 study, Alexion plans to initiate Phase 2 studies of ALXN1720 in gMG and dermatomyositis (DM), pending regulatory feedback.
ANDEXXA – Urgent Surgery: ANDEXXA is currently being evaluated in a single-arm, open-label study in patients taking apixaban, rivaroxaban, edoxaban, or enoxaparin who require urgent surgery. The results of this study will inform the design of a randomized controlled clinical trial to expand the label in this population.
Cerdulatinib: Acquired as part of the Portola acquisition, cerdulatinib is a dual spleen tyrosine kinase and janus kinase (SYK/JAK) inhibitor being evaluated in a Phase 1/2a study in patients with relapsed/refractory chronic lymphocytic leukemia or B-cell or T-cell non-Hodgkin lymphoma.
Updated 2020 financial guidance assumes a GAAP effective tax rate of (5.0) to (4.5) percent and a non-GAAP effective tax rate of 15.5 to 16.0 percent. The 2020 GAAP and non-GAAP tax rates do not benefit from one-time events that benefited the tax rates in 2019.

Alexion’s financial guidance is based on current foreign exchange rates net of hedging activities and does not include the effect of acquisitions, license and other strategic agreements, intangible asset impairments, litigation charges, changes in fair value of contingent consideration, gains or losses related to strategic equity investments or restructuring and related activity outside of the previously announced activities that may occur after the issuance of this press release.

Conference Call/Webcast Information:

Alexion will host a conference call/audio webcast to discuss the third quarter 2020 results today at 8:00 a.m. Eastern Time. To participate in the call, dial 866-762-3111 (USA) or 210-874-7712 (International), conference ID 6582445 shortly before 8:00 a.m. Eastern Time. A replay of the call will be available for a limited period following the call. The audio webcast can be accessed on the Investor page of Alexion’s website at: View Source