On November 4, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the third quarter 2021, recent business highlights and key catalysts over the next several months (Press release, Atara Biotherapeutics, NOV 4, 2021, View Source [SID1234594484]).

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"Atara continues to make meaningful progress across our strategic priorities and with positive data from our pivotal Phase 3 ALLELE study and imminent EU regulatory submission, we are now at an inflection point as we work to deliver tab-cel, a potentially transformative first-in-kind therapy, to patients in need," said Pascal Touchon, President and Chief Executive Officer of Atara. "We are equally encouraged by new data confirming our conviction for ATA188 as the first investigational therapy to reverse disability in progressive multiple sclerosis, and upcoming milestones related to our potentially best-in-class CAR T portfolio that does not require TCR or HLA gene editing."

Tabelecleucel (tab-cel) for Post-Transplant Lymphoproliferative Disease (PTLD)

First presentation of new positive data from the pivotal Phase 3 ALLELE study, reinforcing the transformative potential of tab-cel, has been accepted as an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021
Top-line data with additional patients and extended follow up confirm a strong objective response rate (ORR) and a safety profile in line with prior results, demonstrate durability of response, and will support the imminent EU Marketing Authorization Application (MAA) submission
An ORR, as measured by independent oncologic response adjudication (IORA) assessment, of 50% (19/38, 95% CI: 33.4, 66.6) was observed, with an ORR of 50% (12/24, 95% CI: 29.1, 70.9) in PTLD following SOT and 50% (7/14, CI: 23.0, 77.0) in PTLD following HCT, with a best overall response of Complete Response (CR; n=5, SOT; n=5, HCT) or Partial Response (PR; n=7, SOT; n=2, HCT)
Overall, the median time to response (TTR) was 1.1 months (0.7-4.7). Of 19 responders, 11 had a duration of response (DOR) lasting more than six months and median DOR has not been reached yet
The one-year survival rate was 61.1% overall (57.4% for SOT, and 66.8% for HCT). Those who responded had a longer survival compared to the non-responders, with a median overall survival (OS) not evaluable (NE) (95% CI: 16.4, NE) and 1-year survival rate of 89.2% (95% CI: 63.1, 97.2)
Safety findings were consistent with previously published data, with no new signals. There were no reports of tumor flare reaction, and no confirmed evidence of graft versus host disease (GvHD), organ rejection, infusion reactions, or cytokine release syndrome (CRS) related to tab-cel
At ASH (Free ASH Whitepaper), Atara will present additional data on tab-cel through several abstracts, including a second oral presentation on long term OS from Phase 2 and multi-center Expanded Access Protocol (EAP) studies in relapsed/refractory EBV+ PTLD showing median OS of 54.6 months in all patients and OS at two years reaching over 86% in responders whether patients experienced CR or PR
Following successful interactions with the European Medicines Agency (EMA), and their recent granting of accelerated assessment to tab-cel, Atara will imminently submit a MAA for tab-cel, with an EU approval decision anticipated in H2 2022
The previously announced exclusive agreement with Pierre Fabre for the commercialization of tab-cel in Europe, the Middle East, Africa, and other select emerging markets for EBV-positive cancers has started strongly. Atara will retain full rights to tab-cel in other major markets, including North America, Asia Pacific, and Latin America
Atara has continued to make good progress through Type B meetings with the U.S. Food and Drug Administration (FDA)
After gaining clarity, alignment on key comparability methodology has been reached
Based on the requests from FDA following recent interactions, Atara will provide the Agency with additional analyses of CMC data already generated
FDA has not requested additional studies or manufacturing lots
Atara subsequently plans to have further interactions with the FDA in Q1 2022 and complete the Biologics License Application (BLA) submission for tab-cel in Q2 2022
Tab-cel for Potential Additional Indications

Atara is committed to pursuing the development of tab-cel in additional EBV-positive patient populations, with a primary focus on immunodeficiency-associated lymphoproliferative diseases (IA-LPDs)
Enrollment is continuing at sites in the Phase 2 multi-cohort study, which is evaluating six patient populations, including four within IA-LPDs and two in other EBV-driven diseases, in the U.S. and EU. Phase 2 study data is expected in 2023
ATA188 for Progressive Multiple Sclerosis

Positive momentum around the ATA188 program continues to build, with increasing awareness of and excitement for the transformative potential of ATA188 in multiple sclerosis (MS) among the medical community and industry
At the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in October, Atara presented translational data based on magnetization transfer ratio (MTR), an imaging biomarker of myelin density, and updated Phase 1 open-label extension (OLE) clinical data in patients with progressive MS treated with ATA188 for up to 39 months
Findings continue to demonstrate that patients may achieve sustained disability improvement (SDI) at a higher rate and longer duration than would be expected based on the natural history of progressive MS; the majority of SDI is driven by improvement in the expanded disability status scale (EDSS)
In seven of eight patients, SDI was maintained at all subsequent timepoints up to 33 months, with multiple patients regaining enough function that they no longer needed a walking aid and were able to walk a few hundred meters unassisted. Most patients in the OLE were progression free, which could be another significant measure of clinical benefit in people with progressive MS
Magnetic Resonance Imaging (MRI) results showed increases in MTR suggestive of remyelination. In patients treated with ATA188 who achieved sustained EDSS improvement versus those who did not, MTR for non-enhancing T2 chronic brain lesions increased at six months and this increase achieved statistical significance at 12 months; A similar trend of MTR increase was also seen in normal-appearing brain tissue
These MTR data, where the time course for increase in MTR parallels the EDSS improvements observed, provides evidence that remyelination may be the driver for clinical improvement, and supports a potential biological basis for clinical EDSS improvements observed with ATA188
Updated results from the ongoing OLE demonstrate continued safety and tolerability of ATA188 with up to three annual treatments. As of August 2021, no fatal adverse events, grade >3 events, dose-limiting toxicities, CRS, or GvHD were observed
Atara is continuing to make good progress with enrollment of the Phase 2 randomized, double-blind, placebo-controlled dose-expansion EMBOLD study evaluating the efficacy and safety of ATA188 in patients with progressive MS, across clinical sites in North America and Australia
An interim analysis to assess efficacy and safety is planned for H1 2022. The Company plans to communicate its decision on next steps for the program, including rationale, while still maintaining the integrity of the study
Atara expects to complete enrollment for EMBOLD in H1 2022
Atara will present encore data at the 29th Annual Meeting of the European Charcot Foundation in November 2021. The Company will present an overview of the methodology planned to determine the potential pharmacodynamic effect of ATA188, by quantifying a decrease of EBV infected cells following treatment with ATA188
CAR T Programs

ATA2271/ATA3271 (Solid Tumors Over-Expressing Mesothelin)

The global strategic collaboration for ATA2271 and ATA3271 with Bayer continues to progress, with work advancing across both mesothelin-partnered CAR-T immunotherapy programs
The first presentation of preclinical, clinical, and translational data from the lowest dose cohorts of the open-label, single-arm Phase 1 clinical study of ATA2271, an autologous CAR-T therapy targeting mesothelin, designed to improve efficacy, persistence, and durability of response for patients with advanced mesothelioma, will take place during a Mini Oral session at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress on December 9, 2021 (presentation #46MO)
Atara is continuing to make progress on IND-enabling studies for ATA3271, an off-the-shelf, allogeneic CAR-T therapy targeting mesothelin using next-generation PD-1 dominant negative receptor (DNR) and 1XX CAR co-stimulatory signaling domain technologies and expects an IND filing in H2 2022
Preclinical data for ATA3271 will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 10-14, 2021 (poster #136)
ATA3219 (B-cell Malignancies)

Atara is making good progress and expects to submit an IND for ATA3219, an off-the-shelf, allogeneic CD19 CAR T immunotherapy targeting B-cell malignancies, in Q1 2022
Leveraging our next-generation 1XX CAR co-stimulatory signaling domain and allogeneic EBV T-cell platform, ATA3219 is a potential best-in-class therapy that does not require T-cell receptor (TCR) or human leukocyte antigen (HLA) gene editing
Allogeneic T Cell Platform Development

To date, the safety and tolerability of Atara’s allogeneic EBV T-cell therapies and platform has been validated by clinical studies and experience in approximately 400 patients in various disease areas
We have established a new Atara Research Center (ARC) to house the Company’s Translational and Pre-Clinical Sciences, Process Sciences, and Analytical Development teams. New capabilities will support our product pipeline and further drive innovation by leveraging our unique and differentiated allogeneic cell therapy platform
Third Quarter 2021 Financial Results

Cash, cash equivalents and short-term investments as of September 30, 2021 totaled $357.2 million, as compared to $373.4 million as of June 30, 2021
The September 30, 2021 cash balance includes $46.4 million from the sale of 3,123,570 shares of common stock through the Company’s at-the-market (ATM) facility
Atara believes that its cash as of September 30, 2021, together with the $45.0 million upfront payment received as a result of our entry into the Pierre Fabre Commercialization Agreement, is sufficient to fund planned operations into the second quarter of 2023
License and collaboration revenue was $5.4 million for the third quarter 2021 and consisted of revenue from activities performed under the Bayer Collaboration Agreements. Atara did not recognize any license and collaboration revenue for the same period in 2020
Net cash used in operating activities was $59.0 million for the third quarter 2021, as compared to $53.0 million for the same period in 2020
Atara reported net losses of $84.7 million, or $0.90 per share, for the third quarter 2021, as compared to $74.3 million, or $0.92 per share, for the same period in 2020
Total operating expenses include non-cash expenses of $16.0 million for the third quarter 2021, as compared to $15.4 million for the same period in 2020
Research and development expenses were $70.3 million for the third quarter 2021, as compared to $59.9 million for the same period in 2020
The increase in the third quarter 2021 was primarily due increased research and clinical trial costs related to the Company’s ATA188 and CAR T programs, and higher employee-related costs from increased headcount
Research and development expenses include $7.8 million of non-cash stock-based compensation expenses for the third quarter 2021, as compared to $8.2 million for the same period in 2020
General and administrative expenses were $19.8 million for the third quarter 2021, as compared to $14.8 million for the same period in 2020
The increase was primarily driven by higher compensation-related costs from increased headcount and activities to support our anticipated tab-cel launch
General and administrative expenses include $5.9 million of non-cash stock-based compensation expenses for the second quarter 2021, as compared to $5.1 million for the same period in 2020
Conference Call and Webcast Details

Atara will host a live conference call and webcast today, Thursday, November 4, 2021, at 8:30 a.m. EDT to discuss the Company’s financial results and recent operational highlights. Analysts and investors can participate in the conference call by dialing 888-437-3179 for domestic callers and 862-298-0702 for international callers, using the conference ID 13723551. A live audio webcast can be accessed by visiting the Investors & Media – News & Events section of atarabio.com. An archived replay will be available on the Company’s website for 30 days following the live webcast.

On November 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported financial results for the third quarter 2021, and provided a corporate update on recent highlights and anticipated near-term milestones (Press release, Surface Oncology, NOV 4, 2021, View Source [SID1234594483]).

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"Surface continues to make considerable progress across our pipeline of novel cancer immunotherapies, highlighted by the announcement of our planned randomized Phase 2 study evaluating SRF388, our potential first-in-class antibody therapy against IL-27, in combination with Roche’s atezolizumab and bevacizumab," said Rob Ross, M.D., chief executive officer of Surface Oncology. "We believe more than ever in our approach targeting the adenosine pathway for the treatment of cancer and the potential of our next-generation antibody therapies in promoting immune activation in the tumor microenvironment. Looking ahead, we remain on track to provide clinical updates on our wholly-owned clinical programs, both as a single-agent and combination therapy, with data from SRF617 expected later this year, and SRF388 data expected in early 2022."

Third Quarter and Subsequent Corporate Highlights:

On November 2, 2021, Surface announced that two abstracts were accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 10-14, 2021, in Washington D.C. and virtually. The two abstracts will highlight new preclinical data from the Company’s two wholly-owned clinical-stage programs, SRF617 and SRF388.

On October 4, 2021, Surface announced details about its plan to initiate a randomized Phase 2 clinical study evaluating SRF388 in combination with Roche’s atezolizumab and bevacizumab, in patients with treatment-naïve hepatocellular carcinoma (HCC). Initiation-enabling activities are underway and the Company expects to dose the first patient in early 2022.

On July 8, 2021, Surface announced the appointment of Denice Torres to its board of directors as lead independent director. Ms. Torres has over 25 years of executive leadership experience in healthcare across the consumer, biopharmaceutical and medical device sectors.
Selected Anticipated Near-term Corporate Milestones:

Investigational New Drug (IND) filing for GSK4381562, formerly SRF813, targeting the PVRIG checkpoint and partnered with GlaxoSmithKline, will be filed in Q4 2021.

Data update for SRF617 anticipated at the European Society for Medical Oncology Immuno-Oncology Congress taking place December 8-11, 2021.

Data update for SRF388 anticipated in early 2022.
Financial Results:

As of September 30, 2021, cash, cash equivalents and marketable securities were $149.7 million, compared to $175.1 million on December 31, 2020.

Research and development (R&D) expenses were $14.0 million for the third quarter ended September 30, 2021, compared to $9.5 million for the same period in 2020. This increase was primarily driven by progress on both our SRF617 and SRF388 Phase 1 clinical trials. R&D expenses included $0.8 million in stock-based compensation expense for the third quarter ended September 30, 2021.

General and administrative (G&A) expenses were $5.8 million for the third quarter ended September 30, 2021, compared to $4.9 million for the same period in 2020. This increase was primarily due to increases in personnel and facility related costs. G&A expenses included $1.2 million in stock-based compensation expense for the third quarter ended September 30, 2021.

For the third quarter ended September 30, 2021, net loss was $19.9 million, or basic and diluted net loss per share attributable to common stockholders of $0.44. Net loss was $15.8 million for the same period in 2020, or basic and diluted net loss per share attributable to common stockholders of $0.39.

Financial Outlook:

In October 2021, Surface expanded its existing debt facility with K2 HealthVentures, increasing the capacity to $50M. Based upon its current operating plan and an anticipated near-term milestone from GSK, Surface maintains a projected cash runway through 2023.

On November 4, 2021 Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported financial results and provided business updates for the third quarter of fiscal year 2021 (Press release, Moderna Therapeutics, NOV 4, 2021, View Source [SID1234594482]).

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"We are humbled to have helped hundreds of millions of people around the world with our COVID-19 vaccine and yet we know our work is not done. We will not rest until our vaccine is available to anyone who needs it, and we are working hard to ensure our vaccine is available in low-income countries with approximately 10% of our 2021 volume and significantly more of our 2022 volume going to low-income countries. It is promising to see the real-world evidence showing that the Moderna COVID-19 vaccine shows sustainably high, durable efficacy," said Stéphane Bancel, Chief Executive Officer of Moderna. "Looking ahead, we are focused on advancing the many other programs in our pipeline. We recently dosed the first participants in the Phase 3 study of our CMV vaccine. CMV is a latent virus that remains in the body for life after infection and can lead to lifelong medical conditions. We are also focused on addressing respiratory viruses in addition to COVID-19, including seasonal flu and RSV. We look forward to sharing data from the Phase 1 study of our flu vaccine candidate soon and we are preparing to start our Phase 2 study. We are also preparing to start the Phase 2/3 study of our RSV vaccine candidate. RSV causes hospitalizations and deaths in our most vulnerable populations of young children and older adults. In addition, we continue to progress our therapeutics pipeline and we look forward to clinical proof of concept data. I would like to thank the Moderna team for their scientific passion and commitment to our mission. I am more energized than ever by the impact our mRNA platform will have on human health."​

Updates and recent progress include:

COVID-19 Vaccine Development

Moderna COVID-19 Vaccine (SpikevaxTM): Received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (U.S. FDA), and approvals by the European Commission and Swissmedic for a booster dose of the Moderna COVID-19 vaccine at the 50 µg dose level
U.S. FDA granted Priority Review to the Biologics License Application (BLA) for the Moderna COVID-19 vaccine
New data from Phase 2/3 KidCOVE study of mRNA-1273 in children ages 6 to under 12 years shows vaccine efficacy of 100% two weeks after first dose of mRNA-1273 at 50 µg dose level, using the Phase 3 COVE study primary case definition for COVID-19
The Phase 1 study of next-generation vaccine candidate against COVID-19 (mRNA-1283) is fully enrolled; Moderna expects to begin Phase 2 study of mRNA-1283 soon; mRNA-1283 is being developed as a potential refrigerator-stable mRNA vaccine
Respiratory Vaccines

Phase 1 portion of the Phase 1/2 study of quadrivalent seasonal flu vaccine candidate (mRNA-1010) fully enrolled, preparations for Phase 2 portion of the study are ongoing
Pivotal Phase 2/3 study of respiratory syncytial virus (RSV) vaccine candidate (mRNA-1345) in older adults expected to begin in 2021; study expected to enroll approximately 34,000 participants, subject to agreement with regulatory authorities
New combination respiratory vaccines: Moderna COVID-19 vaccine + flu vaccine candidate (mRNA-1073) and pediatric RSV + hMPV vaccine candidate (mRNA-1365)
Latent Vaccines

First participants dosed in Phase 3 study of cytomegalovirus (CMV) vaccine candidate (mRNA-1647)
Phase 1 study of EBV vaccine candidate (mRNA-1189) expected to start soon
New EBV therapeutic vaccine candidate (mRNA-1195)
Therapeutics

Phase 2 randomized, placebo-controlled study of personalized cancer vaccine (PCV) (mRNA-4157) in combination with Merck’s pembrolizumab (KEYTRUDA), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma is fully enrolled; data readout expected in the fourth quarter of 2022
Enrollment of the first cohort in Propionic Acidemia candidate (mRNA-3927) Phase 1/2 Paramount study is complete
First patient dosed in Phase 1 study of Methylmalonic Acidemia (MMA) candidate (mRNA-3705)
Investigational New Drug application (IND) open and Orphan Drug Designation granted by U.S. FDA for GSD1a program (mRNA-3745)
Providing investigational mRNA Crigler-Najjar Syndrome Type 1 (CN-1) therapy (mRNA-3351) to Institute for Life Changing Medicines (ILCM) free of charge; CN-1 is an ultra-rare disease
Introducing inhaled pulmonary therapeutics modality; IND-enabling first-in-human studies of Vertex and Moderna mRNA cystic fibrosis (CF) therapeutic (VXc-522) are ongoing in new pulmonary modality
Moderna continues to scale, now with 37 programs in development across 34 development candidates1, including 21 in ongoing clinical studies. The Company’s updated pipeline can be found at www.modernatx.com/pipeline. Moderna and collaborators have published nearly 100 peer reviewed manuscripts.

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, vaccines against latent viruses, and 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.

Vaccines against acute respiratory infections

COVID-19 vaccine development

Moderna COVID-19 Vaccine (mRNA-12732, SpikevaxTM): The U.S. FDA granted Priority Review to the BLA for mRNA-1273. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2022. The World Health Organization (WHO) and health agencies in more than 60 countries have granted emergency use authorization or emergency use listing for the use of the Moderna COVID-19 vaccine in adults.

Booster Dose of mRNA-1273: The U.S. FDA, EMA, Swissmedic and other health agencies around the world have authorized a booster dose of the Moderna COVID-19 vaccine at the 50 µg dose level.

Addressing Variants of Concern: Moderna has four development candidates against SARS-CoV-2 variants of concern, including three which have been administered in a Phase 2/3 clinical trial. The Company’s strategy is to develop booster vaccines against current variants of concern and against potential future variants of concern.
mRNA-1273.351: Variant-specific candidate against the Beta variant
mRNA-1273.617: Variant-specific candidate against the Delta variant
mRNA-1273.211: Multivalent candidate combining the Beta-specific variant and mRNA-1273
mRNA-1273.213: Multivalent candidate combining the Beta-specific and Delta-specific candidates
Further Clinical Studies of mRNA-1273

Phase 2/3 "TeenCOVE" study of mRNA-1273 in adolescents: mRNA-1273 is authorized for use in adolescents ages 12 to 17 in the United Kingdom, European Union, Japan, Canada, Switzerland, Taiwan, Saudi Arabia, Australia and the Philippines. The U.S. FDA notified the Company that it will require additional time to complete its assessment of Moderna’s EUA request for the use of mRNA-1273 at the 100 µg dose level in adolescents 12 to 17 years of age.

Phase 2 "KidCOVE" study of mRNA-1273 in young children: The Phase 2 study of mRNA-1273 in pediatric population ages 6 months to under 12 years is ongoing. Moderna is sharing new data from the KidCOVE study of mRNA-1273 in children ages 6 years to under 12 years. Vaccine efficacy of 100% using the P301 primary case definition for COVID-19 was observed two weeks after the first dose of mRNA-1273 at the 50 µg dose level. Additionally, for asymptomatic infection two weeks after the first dose, vaccine efficacy was 65% (95% CI: .16, .85). For SARS-CoV-2 infection regardless of symptoms,​ vaccine efficacy was 80% (95% CI: .62, .90) two weeks after the first dose. On October 24, the Company announced positive top line top line data from the Phase 2/3 study of mRNA-1273 in children 6 to under 12 years of age. Geometric mean ratio (GMR) comparing the response in children to the response in young adults from the Phase 3 COVE study was 1.5 (95% CI: 1.3, 1.8), with a seroresponse rate of 99.3%. Two 50 μg doses of mRNA-1273 were generally well tolerated. Moderna plans to submit results to the EMA and regulatory agencies around the world soon. Dose selection studies are underway for the 2 to under 6 years and 6 months to under 2 years age groups.

Phase 3 "COVE Transplant" study of mRNA-1273: The Phase 3 study of mRNA-1273 in adults with a kidney or liver transplant is ongoing, including the offer of a third vaccine dose to these immunocompromised participants.

Next-generation vaccine candidate against COVID-19 (mRNA-1283): The Phase 1 study of mRNA-1283 is fully enrolled and ongoing. An interim analysis of data from the Phase 1 study of mRNA-1283 at three dose levels indicate that a lower dose of mRNA-1283 achieved similar neutralizing antibody responses compared to a primary series of mRNA-1273. mRNA-1283 had an acceptable tolerability profile. The Company expects to start a Phase 2 booster study in the near term. mRNA-1283 is a next-generation vaccine candidate against COVID-19 that encodes for the portions of the SARS-CoV-2 spike protein critical for neutralization, specifically the Receptor Binding Domain (RBD) and N-terminal Domain (NTD). The encoded mRNA-1283 antigen is shorter than mRNA-1273 and is being developed as a potential refrigerator-stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers.
Additional vaccines against acute respiratory infections

Seasonal influenza vaccine (mRNA-1010): The Phase 1 study evaluating the safety and reactogenicity of three different dose levels of mRNA-1010 in adults over age 18 is fully enrolled (N=180). mRNA-1010 encodes for hemagglutinin (HA) glycoproteins of four flu strains and targets lineages recommended by the WHO for the prevention of influenza, including seasonal influenza A H1N1, H3N2 and influenza B Yamagata and Victoria.

COVID-19 and flu combination vaccine (mRNA-1073): mRNA-1073 encodes for the COVID-19 spike protein and the Flu HA glycoproteins. Moderna owns worldwide commercial rights to mRNA-1073.

Respiratory syncytial virus (RSV) vaccine (mRNA-1345): At its annual R&D Day on September 9, the Company shared positive Phase 1 interim data from the older adult cohort. Moderna is preparing for a Phase 2/3 study of RSV in older adults (ages older than 60 years) and expects to begin this study by the end of 2021. The Company expects this Phase 2/3 study will be a global study conducted in locations influenced by the epidemiology of RSV and expects to enroll approximately 34,000 participants, subject to agreement with regulatory authorities. The FDA has granted Fast Track designation for mRNA-1345 in adults older than 60 years of age. RSV is the leading cause of severe respiratory illness in young children and older adults (65+). The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, women of child-bearing potential, older adults and seropositive toddlers is ongoing. All four cohorts of younger adults (ages 18-49 years) and all four cohorts of older adults (ages 65-79 years) are fully enrolled. There is no approved vaccine to prevent RSV. Moderna owns worldwide commercial rights to mRNA-1345.

Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): Moderna is enrolling seropositive pediatric participants (12-36 months of age) in the Phase 1 study of hMPV/PIV3 study (mRNA-1653). The first cohort in this study is fully enrolled. Moderna owns worldwide commercial rights to mRNA-1653.

Pediatric RSV and hMPV combination vaccine (mRNA-1365): mRNA-1365 encodes for the RSV prefusion F glycoprotein and the hMPV F protein. Moderna owns worldwide commercial rights to mRNA-1365.
Vaccines against latent viruses

Cytomegalovirus (CMV) vaccine (mRNA-1647): The first participants have been dosed in the Phase 3 study, known as CMVictory, which is evaluating the safety and efficacy of mRNA-1647 against primary CMV infection in women ages 16-40 years. The Company will seek to enroll up to approximately 8,000 participants in the study, including 6,900 women of child-bearing potential, at approximately 150 sites globally, beginning in the U.S. Moderna has set a goal of enrolling a diverse group of U.S. participants into the study, including approximately 42% of participants who are Persons of Color. Based on the interim analysis of the Phase 2 study, the 100 μg dose has been chosen for the Phase 3 pivotal study. The ClinicalTrials.gov identifier is NCT05085366. To learn more about eligibility, visit www.CMVictory.com. Moderna owns worldwide commercial rights for mRNA-1647.

Epstein-Barr virus (EBV) vaccine (mRNA-1189): The Phase 1 study of mRNA-1189 is expected to begin soon. EBV is a member of the herpesvirus family and is spread through bodily fluids (e.g., saliva) and contracted primarily by young children and adolescents. It is a major cause of infectious mononucleosis (IM), and associated risks to other long-term medical conditions, including an increased risk of developing multiple sclerosis by approximately 4 to 10-fold, certain lymphoproliferative disorders and cancers, and autoimmune diseases3,4. While EBV infection in early childhood is predominantly asymptomatic, primary infection in adolescence can lead to IM, which can debilitate patients for weeks to months, sometimes requiring hospitalization for serious complications. mRNA-1189 is a vaccine being developed to prevent IM, and potentially EBV infection. Similar to Moderna’s CMV vaccine (mRNA-1647), mRNA-1189 contains four mRNAs that encode EBV envelope glycoproteins (gH, gL, gp42, gp220). There is currently no approved vaccine for EBV or IM. Moderna owns worldwide commercial rights to mRNA-1189.
Epstein-Barr virus (EBV) therapeutic vaccine candidate (mRNA-1195): mRNA-1195 is being developed to prevent longer term sequelae of EBV infection, which are associated with loss of immune control of EBV latent infection, creating longer-term complications. mRNA-1195 is in pre-clinical development and encodes for additional antigens than mRNA-1189. The Company expects to initially test the vaccine in post-transplant lymphoproliferative disorder (PTLD) because at least 80% of PTLD in transplant patients is associated with EBV. The Company expects to also pursue other longer-term potential indications for this vaccine, including multiple sclerosis.

HIV vaccine (mRNA-1644 & mRNA-1574): HIV is the virus responsible for acquired immunodeficiency syndrome (AIDS), a lifelong, progressive illness with no effective cure. Approximately 38 million people worldwide are currently living with HIV with 1.2 million in the U.S. Approximately 2 million new infections of HIV are acquired worldwide every year and approximately 690,000 people die annually due to complications from HIV/AIDS. mRNA-1644, a collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation, is a novel approach to HIV vaccine strategy in humans designed to elicit broadly neutralizing HIV-1 antibodies (bNAbs). A Phase 1 study for mRNA-1644 will use iterative human testing to validate the approach and antigens and multiple novel antigens will be used for germline-targeting and immuno-focusing. A second approach, mRNA-1574, is being evaluated in collaboration with the NIH and includes multiple native-like trimer antigens. The Company expects to begin Phase 1 studies for both mRNA-1644 and mRNA-1574 in 2021.
Public health vaccines

Zika virus vaccine (mRNA-1893): The Phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico. mRNA-1893 is being developed in collaboration with BARDA. Moderna owns worldwide commercial rights to mRNA-1893.

Nipah virus (NiV) Vaccine (mRNA-1215): NiV is a zoonotic virus transmitted to humans from animals, contaminated food, or through direct human-to-human transmission and causes a range of illnesses including fatal encephalitis. Severe respiratory and neurologic complications of NiV have no treatment other than intensive supportive care. The case fatality rate among those infected is estimated at 40-75%. NiV outbreaks cause significant economic burden to impacted regions due to loss of human life and interventions to prevent further spread, such as the slaughter of infected animals. NiV has been identified as the cause of isolated outbreaks in India, Bangladesh, Malaysia, and Singapore since 2000 and is included on the WHO R&D Blueprint list of epidemic threats needing urgent R&D action. mRNA-1215 was co-developed by Moderna and the NIH’s Vaccine Research Center (VRC).
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): The Phase 1 study evaluating escalating doses of mRNA-1944 has completed. The Company anticipates publication of the full results of the Phase 1 study soon. At this time, the Company does not have plans to advance to a Phase 2 study.

IL-2 (mRNA-6231): mRNA-6231 is an mRNA encoding for a long-acting tolerizing IL-2. This autoimmune development candidate is designed to preferentially activate and expand the regulatory T cell population. The first participant in the Phase 1 study of mRNA-6231 in healthy adult participants (between 18 and 50 years of age) has been dosed. 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 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 (mRNA-0184): mRNA-0184 encodes for the relaxin fusion protein. The mRNA sequence of mRNA-0184 is engineered to increase protein expression and prolong half-life. Moderna is planning for a Phase 1 study in participants with chronic heart failure. The Company expects that mRNA-0184 will be administered after heart failure decompensation to bridge patients through the vulnerable period. Moderna owns worldwide commercial rights to mRNA-0184.
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, placebo-controlled 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 fully enrolled (n=150). The Company expects the Phase 2 data readout to occur in the fourth quarter of 2022. The primary endpoint of the Phase 2 study is recurrence-free survival at 12 months. The Phase 1 in multiple cohorts is ongoing and the expanded head and neck cohort is recruiting additional patients. 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/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 fully enrolled. Enrollment in additional cohorts is ongoing. Moderna owns worldwide commercial rights to mRNA-2752.

Presentation of Note: Moderna will share a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting on November 12.

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 surgery with moderately impaired systolic function, led by AstraZeneca, has completed recruitment after enrollment of the low dose cohort (n=11). Moderna has licensed worldwide commercial rights to AZD8601 to AstraZeneca.

Presentation of Note: AstraZeneca to present on the VEGF-A program on November 15 at the American Heart Association’s Scientific Sessions 2021 annual meeting.
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.

Propionic acidemia (PA) (mRNA-3927): The Phase 1/2 Paramount study of mRNA-3927 is ongoing and the first cohort is fully enrolled. mRNA-3927 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-3927.

Methylmalonic acidemia (MMA) (mRNA-3705): The Phase 1/2 Landmark study to evaluate the safety and pharmacology of mRNA-3705 in patients 1 year of age and older with MMA is ongoing and the first participant has been dosed. Moderna received rare pediatric designation for mRNA-3705. Moderna owns worldwide commercial rights to mRNA-3705.

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): The U.S. FDA has granted mRNA-3745 Orphan Drug Designation and completed its review of the IND application allowing it to proceed to clinic. 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. Moderna owns worldwide commercial rights to mRNA-3745.

Crigler-Najjar Syndrome Type 1 (CN-1) (mRNA-3351): mRNA-3351 encodes for the human UGT1A1 and is designed to restore the missing or dysfunctional proteins that causes Crigler-Najjar Syndrome Type 1. mRNA-3351 has been granted Rare Pediatric Disease designation by the U.S. FDA. Moderna will provide investigational mRNA-3351 to the nonprofit Institute for Life Changing Medicines (ILCM) free of charge. ILCM will be responsible for the clinical development of mRNA-3351 and plans to initiate clinical studies of mRNA-3351 in 2022.
Inhaled Pulmonary Therapeutics

Cystic Fibrosis (CF) (VXc-522): VXc-522 is an mRNA therapeutic being designed in collaboration with Vertex Pharmaceuticals. It is designed to treat the underlying cause of CF by enabling cells in the lungs to produce functional cystic fibrosis transmembrane conductance regulator (CFTR) protein for the treatment of the 10% of patients who do not produce any CFTR protein. IND-enabling studies are underway, and Vertex expects to submit an IND for this program in 2022. VXc-522 is being advanced by Vertex.
Information about each development candidate in Moderna’s pipeline can be found at investors.modernatx.com.

Third Quarter 2021 Financial Results

Revenue: Total revenue was $5.0 billion for the three months ended September 30, 2021, compared to $157 million for the same period in 2020. Total revenue was $11.3 billion for the nine months ended September 30, 2021, compared to $232 million for the same period in 2020. Total revenue increased in 2021 as a result of commercial sales of the Company’s COVID-19 vaccine, and to a lesser extent, grant revenue. Product sales for the three and nine months ended September 30, 2021 were $4.8 billion and $10.7 billion, respectively, from sales of 208 million and 510 million doses of the Company’s COVID-19 vaccine for the three and nine months ended September 30, 2021, respectively. The increase in grant revenue of $286 million for the nine months ended September 30, 2021 was primarily driven by an increase in revenue from BARDA related to the Company’s COVID-19 vaccine development. Grant revenue for the three months ended September 30, 2021 was relatively flat compared to the same period in 2020.

Cost of Sales: Cost of sales was $722 million, or 15%, of product sales for the three months ended September 30, 2021, including third-party royalties of $168 million. Cost of sales was $1.7 billion, or 16%, of the Company’s product sales, for the nine months ended September 30, 2021, including third-party royalties of $400 million. A portion of the inventory costs associated with the Company’s product sales for the nine months ended September 30, 2021 was expensed as pre-launch inventory costs in 2020. At the end of the first quarter of 2021, the Company’s zero-cost COVID-19 vaccine inventory was substantially utilized. If inventory sold for the nine months ended September 30, 2021 was valued at cost, the Company’s cost of sales for the period would have been $1.9 billion, or 17% of product sales.

Research and Development Expenses: Research and development expenses were $521 million for the three months ended September 30, 2021, compared to $344 million for the same period in 2020. Research and development expenses were $1.3 billion for the nine months ended September 30, 2021, compared to $611 million for the same period in 2020. The growth in spending in 2021 was mainly due to increases in clinical trial expenses and personnel-related costs, largely driven by increased mRNA-1273 clinical development and headcount.

Selling, General and Administrative Expenses: Selling, general and administrative expenses were $168 million for the three months ended September 30, 2021, compared to $48 million for the same period in 2020. Selling, general and administrative expenses were $366 million for the nine months ended September 30, 2021, compared to $109 million for the same period in 2020. The growth in spending in 2021 was mainly due to increases in consulting and outside services, personnel-related costs, marketing expenses and distributor fees, primarily attributable to the Company’s COVID-19 vaccine commercialization-related activities and increased headcount.

Net Income (Loss): Net income was $3.3 billion for the three months ended September 30, 2021, compared to a net loss of $(233) million for the same period in 2020. Net income was $7.3 billion for the nine months ended September 30, 2021, compared to a net loss of $(474) million for the same period in 2020.

Cash Position: Cash, cash equivalents and investments as of September 30, 2021 and December 31, 2020 were $15.3 billion and $5.2 billion, respectively.

Net Cash Provided By Operating Activities: Net cash provided by operating activities was $10.3 billion for the nine months ended September 30, 2021, compared to $763 million for the same period in 2020. Net cash provided by operating activities increased significantly in 2021, mainly due to net income of $7.3 billion and additional customer deposits received during the period for the Company’s future COVID-19 vaccine supply.

Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $164 million for the nine months ended September 30, 2021, compared to $44 million for the same period in 2020.

2021 Updated Financial Framework

For Expected Delivery in Fiscal Year (FY) 2021: Expected to realize product sales for FY 2021 between $15 billion and $18 billion.

Key Variables Impacting FY 2021 Revenues: Fewer doses for delivery in 2021, shifted to early 2022; prioritization of deliveries to low-income countries through COVAX and African Union

Vaccine Dose Deliveries for FY 2021: The Company expects deliveries of its COVID-19 vaccine in FY 2021 to be between 700 million and 800 million doses at the 100 µg dose level. Key variables impacting output include longer delivery lead times for international shipments and exports that may shift deliveries to early 2022, temporary impact from expansion of fill/finish capacity and ramp up of product release to market.

Cost of Sales: Cost of sales as percentage of product sales are expected to be between 16-17% for FY 2021.

2021 Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses: Continue to expect quarter over quarter cost increases in R&D and SG&A expenses during 2021 as commercial and research and development activities and expenses ramp up.

Tax Rate: The Company now expects the effective tax rate for 2021 to be in the high single digit range as a result of the forecasted global sales mix and utilization of the accumulated net operating loss carry-forward of $2.3 billion.

Capital Expenditures: Expect approximately $0.4 billion of capital investments for 2021.

Share Repurchase Program: The Board of Directors has authorized a share repurchase program of up to $1 billion over a two-year period to return excess capital to shareholders. No shares were repurchased through the end of the third quarter.
2022 Revenue Drivers

We expect several dynamics will drive 2022 revenues:

APAs Signed: The Company has signed approximately $17 billion of advance purchase agreements (APAs) for delivery in 2022.
APAs with Options: The Company anticipates the exercise of options under 2022 APAs of up to $3 billion.
U.S. Fall 2022 Booster Market: Subject to receipt of a BLA or sBLA for boosters prior to the fall booster season, the Company anticipates commercial booster market sales could be up to $2 billion.
Based on these three revenue drivers, the Company believes 2022 sales could be in the range of $17 billion to $22 billion. The Company continues to have discussions for 2022 APAs with governments and international organizations, including COVAX, the Pan American Health Organization (PAHO) and the African Union.

Corporate Social Responsibility

Sustainability: Moderna announced a pledge to achieve net-zero carbon emissions globally by 2030.
Global Vaccine Access Strategy: Moderna CEO Stéphane Bancel published a letter on Moderna’s commitment to global vaccine access on October 8.
COVID-19 Vaccine Doses to the African Union: Moderna recently announced a new Memorandum of Understanding (MoU) to make up to 110 million doses of the Moderna COVID-19 vaccine available to the African Union. The Company is prepared to deliver the first 15 million doses in the fourth quarter of 2021, 35 million doses in the first quarter of 2022, and up to 60 million doses in second quarter 2022. All doses are offered at Moderna’s lowest tiered price, in line with the Company’s global access commitments.

COVID-19 Vaccine Doses to COVAX: Moderna also announced an agreement with Gavi, the Vaccine Alliance to supply up to 116.5 million doses of Moderna’s COVID-19 vaccine to be delivered in the second quarter of 2022. The exercise of these options for additional doses represents an increase from an earlier agreement for 60 million doses of Moderna’s COVID-19 vaccine that was communicated earlier this year. As per the advance purchase agreement signed on behalf of the COVAX Facility, Gavi continues to retain the option to procure 233 million additional doses in 2022 for a potential total of 500 million doses between 2021 and 2022 under the agreement. All doses are offered at Moderna’s lowest tiered price, in line with the Company’s global access commitments.

mRNA Facility in Africa: Moderna announced that it will build a state-of-the-art mRNA facility in Africa with the goal of producing up to 500 million doses of vaccines each year at the 50 µg dose level. The Company anticipates investing up to $500 million in this new facility, which is expected to include drug substance manufacturing with the opportunity for fill/finish and packaging capabilities at the site.

Moderna Fellowship Program: Moderna announced the launch of the Moderna Fellowship Program to support the next generation of scientists and healthcare professionals as they innovate in the field of mRNA research towards improving patient care and population health.
Corporate Updates

Full-Time Employees: As of September 30, 2021, Moderna had approximately 2,400 employees, compared to approximately 1,200 employees as of September 30, 2020.

Moderna Genomics (mGx): Moderna announced a new collaboration with Metagenomi in genomics around novel gene editing enzymes.

Company Recognition: Moderna was named a top employer by Science and Science Careers for the seventh consecutive year and was named the number one company on Fast Company’s 2021 Best Workplaces for Innovators list.

Moderna Science Center: Moderna announced that it is investing in a new science center, known as the Moderna Science Center, at 325 Binney Street in Cambridge, MA to support the Company’s next chapter of discovery. This 462,000 square foot state-of-the-art building is targeting LEED Zero certification and is being designed to be the most sustainable commercial lab building in Cambridge.

Collaboration to Bring mRNA Manufacturing to Canada: Moderna announced an MoU with the government of Canada to build a state-of-the-art mRNA vaccine manufacturing facility in Canada, including access to Moderna’s mRNA development engine. The goals of this MoU are to build the foundation to support Canada with direct access to rapid pandemic response capabilities and to provide access to Moderna’s vaccines in development for respiratory viruses.

R&D Day: Moderna hosted its fifth annual R&D Day on September 9.
Key 2022 Investor and Analyst Event Dates

Vaccines Day: March 24
Science Day: May 17
R&D Day: September 8
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Thursday, November 4, 2021. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 9177025. 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. The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

On November 4, 2021 Aeglea BioTherapeutics, Inc. (Nasdaq: AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the third quarter ended September 30, 2021, and reviewed recent corporate updates and program highlights (Press release, Aeglea BioTherapeutics, NOV 4, 2021, View Source [SID1234594480]).

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"We have made significant progress this year across all our programs and are very excited for the upcoming readout of our Phase 3 clinical trial of pegzilarginase in Arginase 1 Deficiency," said Anthony Quinn, M.B. Ch.B., Ph.D., president and chief executive officer of Aeglea. "Given the potential transformational impact of pegzilarginase for people with Arginase 1 Deficiency, we are thrilled to have a robust data presence from our pegzilarginase program at the International Congress of Inborn Errors of Metabolism later this month, including PEACE baseline patient characteristics. These abstracts show the progressive and debilitating nature of this disease and reinforces the considerable need for a therapy that lowers plasma arginine."

Quinn added, "We believe that our unique platform for modifying human enzymes may address multiple rare metabolic disorders and that we are well positioned for potential approval of pegzilarginase as the first treatment in our portfolio. We have laid the groundwork for the commercialization of pegzilarginase while continuing to develop AGLE-177 for people who suffer from Homocystinuria, another rare and progressive disease with limited treatment options."

Third Quarter and Recent Highlights and Updates

Pegzilarginase in Arginase 1 Deficiency: topline data from PEACE expected in December 2021

Highlighted baseline data from randomized patients in PEACE, a pivotal Phase 3 clinical trial of pegzilarginase. Patient characteristics include markedly elevated plasma arginine, spasticity, seizures and mobility deficits, and demonstrate the considerable unmet need for a therapy that maintains control of plasma arginine to improve patient outcomes. The baseline data will be reviewed during an oral presentation at the 14th International Congress of Inborn Errors of Metabolism (ICIEM) being held November 21-23; the pegzilarginase program will be highlighted in seven abstracts in total at ICIEM.

Presented gait kinematics and spasticity subset analysis data from the Phase 1/2 and Phase 2 open-label extension studies of pegzilarginase at the International Parkinson and Movement Disorder Society Annual Congress (MDS Virtual Congress 2021).
AGLE-177 in Homocystinuria

Continued enrollment and patient identification activities in a Phase 1/2 clinical trial in people with Homocystinuria being conducted at sites located in the United Kingdom and Australia.
Third Quarter 2021 Financial Results

As of September 30, 2021, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $114.3 million. The company expects its cash, cash equivalents and investments will enable it to fund its operating expenses and capital expenditure requirements into 2023.

Aeglea recognized development fee revenues of $1.4 million in the third quarter of 2021, as a result of its license and supply agreement with Immedica for the commercial rights to pegzilarginase in certain territories outside the United States. The revenues recorded in the third quarter of 2021 are related to the delivery of clinical trial and regulatory services. Aeglea recognized no revenue for the corresponding period of 2020.

Research and development expenses totaled $14.9 million for the third quarter of 2021 and $12.5 million for the third quarter of 2020. The increase was primarily associated with ramping-up and completing enrollment in our Phase 3 PEACE trial of pegzilarginase for the treatment of people with Arginase 1 Deficiency and initiating dosing in our Phase 1/2 trial of AGLE-177 for the treatment of people with Homocystinuria.

General and administrative expenses totaled $6.8 million for the third quarter of 2021 and $5.7 million for the third quarter of 2020. This increase was primarily due to building the company’s commercial capabilities and infrastructure.

Net loss totaled $20.3 million and $18.0 million for the third quarter of 2021 and 2020, respectively, with non-cash stock compensation expense of $2.1 million and $1.7 million for the third quarter of 2021 and 2020, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme, which has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality. Current standard of care includes dietary protein restriction and essential amino acid supplementation which does not adequately lower plasma arginine or prevent progression of neurologic manifestations.

Aeglea’s Phase 1/2 and Phase 2 open-label extension data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. The company’s ongoing single, global pivotal Phase 3 PEACE clinical trial is designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of plasma arginine reduction. Pegzilarginase has received multiple regulatory designations including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug Designations from the FDA as well as Orphan Drug Designation from the European Medicines Agency.

About AGLE-177 in Homocystinuria

AGLE-177 is a novel recombinant human enzyme, which degrades the amino acid homocysteine and its related dimer, homocystine. AGLE-177 is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of homocysteine and homocystine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177, which is designed to lower abnormally high blood levels of homocysteine, improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.

On November 4, 2021 Aptose Biosciences Inc. (Nasdaq: APTO; TSX: APS), reported that it has entered into an exclusive license agreement with Hanmi Pharmaceutical, a South Korean pharmaceutical company, to develop and commercialize HM43239, an oral, highly potent, clinical-stage myeloid kinome inhibitor (MKI), designed to target a distinct constellation of kinases operative in myeloid malignancies, including SYK, FLT3, and others (Press release, Aptose Biosciences, NOV 4, 2021, View Source [SID1234594478]). HM43239 has demonstrated significant genotype-agnostic anti-leukemic activity in an ongoing Phase 1/2 clinical trial, including multiple complete responses in patients with relapsed or refractory acute myeloid leukemia (AML).

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Under the terms of the agreement, Hanmi has granted Aptose exclusive worldwide rights to HM43239 for all indications. Hanmi will receive an upfront payment of $12.5 million, including $5 million in cash and $7.5 million in Aptose shares. Hanmi will also receive up to $407.5 million in future milestone payments contingent upon the achievement of certain clinical, regulatory and sales milestones across several potential indications, as well as tiered royalties on net sales.

"Our deep experience with kinase inhibitors has led us to appreciate and develop agents covering constellations of kinases associated with specific malignancies. HM43239 is a well-tolerated, once-daily oral agent with validated anti-leukemic activity in a highly challenging and heterogeneous malignancy like AML. We believe that HM43239 has a clear development and commercial path, while being a natural fit with our strategic focus, technical expertise, and clinical experience," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer.

"We believe that the myeloid kinome inhibitor HM43239 furthers our leadership in leukemia and lymphoma therapeutics, alongside our dual lymphoid and myeloid kinome inhibitor luxeptinib. We believe that today’s agreement brings significant value to our company and shareholders, and we are pleased to add this novel clinical compound to our evolving pipeline," said Jotin Marango, M.D., Ph.D., Senior Vice President, Chief Financial Officer and Chief Business Officer.

"We view HM43239 as a promising drug for the treatment of myeloid hematologic malignancies, which can specifically target mutations that are commonly found in AML patients, while overcoming drug resistance observed with currently approved drugs. We are thrilled to establish a partnership with Aptose, who has strong expertise in the field of hematology, to enhance the quality of life of patients suffering from refractory hematologic tumors," said Se-Chang Kwon, Ph.D., Chief Executive Officer at Hanmi Pharmaceutical.

Aptose has scheduled a conference call and webcast today, Thursday, November 4, 2021:

Conference Call & Webcast Details

About HM43239
HM43239 is an oral genotype agnostic small molecule inhibitor of a constellation of kinases operative in myeloid malignancies and known to be involved in tumor proliferation, resistance to therapy, and differentiation. Preclinical in vitro and in vivo studies suggest that HM43239 may be an effective monotherapy and combination therapy in patients with hematologic malignancies including AML. An international Phase 1/2 clinical trial in patients with relapsed or refractory AML is ongoing. The dose escalation portion of this study thus far has delivered multiple complete responses in a diverse set of patients with various disease genotypes, and no toxicity trends that prevent further dose escalation to date. HM43239 was granted Orphan Drug Designation (ODD) in AML in the US in October 2018. For more information, please visit clinicaltrials.gov (NCT03850574).