On May 10, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported first quarter 2021 financial results (Press release, Precigen, MAY 10, 2021, View Source [SID1234579584]).

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"In the first quarter of 2021, our portfolio, including our most advanced clinical programs, has progressed consistent with guidance," said Helen Sabzevari, PhD, President and CEO of Precigen. "Our UltraCAR-T trials for PRGN-3005 in ovarian cancer and PRGN-3006 in acute myeloid leukemia as well as the PRGN-2009 trial in HPV-associated cancers continue to progress according to plan. We were pleased to initiate the first-in-human Phase 1 study of PRGN-2012, Precigen’s first off-the-shelf AdenoVerse immunotherapy targeting infectious disease to enter the clinic, and receive orphan drug designation from the US FDA in patients with RRP. We look forward to upcoming presentations of new clinical data for AG019 at FOCIS and the current trial status for PRGN-2009 at ASCO (Free ASCO Whitepaper) and we anticipate multiple data readouts from our portfolio in the coming months, meeting our stated milestones."

Business Highlights:

PRGN-3005 UltraCAR-T

Overview: PRGN-3005 UltraCAR-T is a first-in-class investigational therapy under evaluation in a Phase 1/1b clinical trial for the treatment of advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer. Study subjects receive the PRGN-3005 infusion either via intraperitoneal (IP) (Arm A) or intravenous (IV) (Arm B) infusion (clinical trial identifier: NCT03907527). The study is being conducted in collaboration with the University of Washington and Fred Hutchinson Cancer Research Center. Preliminary Phase 1 data reported from the lowest two dose levels of the IP arm showed a favorable safety profile with no dose-limiting toxicities (DLTs), neurotoxicity or cytokine release syndromes (CRS); encouraging expansion and persistence without lymphodepletion; and clinical activity as evidenced by regression in total target tumor burden.
Enrollment Status: Dose escalation in both IP and IV arms of the Phase 1 trial is ongoing concurrently. Enrollment was completed in dose level 3 of the IP arm and dosing was initiated in dose level 4 of the IP arm. Escalation to higher doses is made possible as a result of the implementation of the UltraPorator system for on-site rapid manufacturing. The first patient was dosed in the IV arm after the US Food and Drug Administration (US FDA) cleared dosing of patients in the dose escalation phase of the IV arm concurrently with the IP arm. The US FDA has cleared enrollment of patients in dose level 3 in the IV arm without the need to follow 3+3 dose escalation through dose levels 1 and 2.
Upcoming Milestones: The Company anticipates the presentation of interim data from the IP arm of the Phase 1 dose escalation trial as well as the initiation of the expansion phase of the IP arm in the second half of 2021.
PRGN-3006 UltraCAR-T

Overview: PRGN-3006 UltraCAR-T is a first-in-class investigational therapy currently under evaluation in a Phase 1/1b clinical trial for the treatment of patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS). Study subjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2) (clinical trial identifier: NCT03927261). The study is being conducted in collaboration with the H. Lee Moffitt Cancer Center & Research Institute. PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the US FDA. Preliminary Phase 1 data reported for the two lowest dose levels in Cohort 1 and the lowest dose level in Cohort 2 showed a favorable safety profile with no DLTs or neurotoxicity; encouraging expansion and persistence of PRGN-3006 UltraCAR-T in both cohorts; and clinical activity as evidenced by reduction in AML tumor blast levels. One of the patients treated with PRGN-3006 at the lowest dose level with lymphodepletion (Cohort 1), with approximately nine million UltraCAR-T cells, achieved complete remission with incomplete hematologic recovery (CRi) per European Leukemia Net (ELN) criteria.
Enrollment Status: The dose escalation phase of both the lymphodepletion and non-lymphodepletion cohorts of the Phase 1 trial is ongoing concurrently. Enrollment was completed in dose level 3 of the non-lymphodepletion cohort and dose level 2 of the lymphodepletion cohort.
Upcoming Milestones: The Company anticipates the presentation of interim Phase 1 data as well as the initiation of the dose expansion phase in the second half of 2021.
AG019 ActoBiotics

Overview: AG019 ActoBiotics is a first-in-class, orally administered, investigational therapy designed to address the underlying cause of Type 1 diabetes (T1D) and is currently under evaluation in a Phase 1b/2a clinical trial for the treatment of early-onset T1D (clinical trial identifier: NCT03751007; EudraCT 2017-002871-24). Interim data from both the Phase 1b monotherapy and Phase 2a combination arms showed a favorable safety profile with no dose-related adverse events or serious adverse events; an encouraging trend in insulin C-peptide levels, a biomarker for T1D disease progression; an increase in preproinsulin (PPI)-specific Type 1 regulatory (Tr1) cells; and a decrease in PPI specific CD8+ T cells.
Enrollment Status: Enrollment and dosing is complete in the Phase 1b and Phase 2a portions of the study.
Clinical Data Presentation at FOCIS 2021: Interim data from the AG019 Phase 1b/2a clinical trial will be presented on June 10, 2021 at 2:05 PM PT as an oral presentation at the Federation of Clinical Immunology Societies (FOCIS) 2021 Virtual Annual Meeting. The abstract entitled, "Lactococcus lactis producing Proinsulin and IL-10 therapy increases Antigen Specific Regulatory T-cells in Monotherapy and in Combination with an anti-CD3 Monoclonal Antibody (Teplizumab) in newly diagnosed T1D patients" will be presented by Kevan Herold, MD, CNH Long Professor of Immunobiology and of Medicine (Endocrinology) at the Yale School of Medicine.
PRGN-2009 AdenoVerse Immunotherapy

Overview: PRGN-2009 is a first-in-class, off-the-shelf (OTS) investigational immunotherapy utilizing the AdenoVerse platform designed to activate the immune system to recognize and target HPV-positive (HPV+) solid tumors. PRGN-2009 is currently under evaluation in a Phase 1/2 clinical trial as a monotherapy or in combination with bintrafusp alfa (M7824) in patients with HPV-associated cancers (clinical trial identifier: NCT04432597). The study is being conducted under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). Preliminary Phase 1 data from the monotherapy arm of the Phase 1 trial showed that all patients (n=6) received multiple PRGN-2009 administrations and repeated administration of PRGN-2009 treatment was well-tolerated with no DLTs. Preliminary correlative analysis from patients treated with PRGN-2009 monotherapy at dose level 1 (n=3) demonstrated an increase in HPV 16 and/or HPV 18-specific T-cell response post PRGN-2009 administration in 100% (3 of 3) of patients and an increase in the magnitude and breadth of immune response was seen with repeated administrations of PRGN-2009.
Enrollment Status: The Phase 1 monotherapy arm has completed enrollment. Subsequently, the Phase 2 trial in patients with newly diagnosed stage II/III p16-positive oropharyngeal cancer or patients with newly diagnosed operable stage II/III/IVA/IVB HPV+ sinonasal squamous cell cancer was initiated. The first patient in the Phase 2 trial was dosed.
Preclinical Data Publication: Preclinical data for PRGN-2009 was published in the Journal of Clinical Investigation entitled, "Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009," which provides the first evaluation of PRGN-2009 and shows promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials.
Trial-in-Progress Presentation at ASCO (Free ASCO Whitepaper) 2021: A trial-in-progress update on the PRGN-2009 study will be provided at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 annual meeting. The abstract entitled, "First-in-human Phase 1/2 trial of PRGN-2009 vaccine as monotherapy or with bintrafusp alfa in patients with recurrent/metastatic (R/M) human papillomavirus (HPV)-associated cancers (HPVC) and as neoadjuvant/induction therapy in locoregionally advanced (LA) HPV oropharyngeal (OP) and sinonasal (SN) squamous cell cancer (SCC)" will be presented as a poster presentation by Charalampos S. Floudas, MD, DMSc, MS, Assistant Research Physician, Genitourinary Malignancies Branch at the Center for Cancer Research at the NCI.
Upcoming Milestones: The Company anticipates the presentation of interim Phase 1 data in the second half of 2021.
PRGN-2012 AdenoVerse Immunotherapy

Overview: PRGN-2012 is a first-in-class, investigational OTS AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11 for treatment of recurrent respiratory papillomatosis (RRP). A Phase 1 clinical trial of PRGN-2012 AdenoVerse immunotherapy in adult patients with RRP is ongoing (clinical trial identifier: NCT04724980). In preclinical studies, PRGN-2012 showed robust HPV 6 and HPV 11-specific T-cell responses in RRP patient samples in vitro.
Orphan Drug Designation: In March 2021, the Company received US FDA Orphan Drug Designation for PRGN-2012 AdenoVerse immunotherapy in patients with RRP.
Enrollment Status: In March 2021, the first patient was dosed in the Phase 1 study.
First Quarter 2021 Financial Highlights

Net cash used in operating activities of $16.4 million in 2021 compared to $27.7 million in 2020;
Cash, cash equivalents, short-term and long-term investments totaled $209.3 million as of March 31, 2021; and
Total revenues of $24.5 million in 2021 compared to $29.8 million in 2020.
First Quarter 2021 Financial Results Compared to Prior Year Period
Research and development expenses decreased $0.8 million, or 7%, from the quarter ended March 31, 2020. Salaries, benefits, and other personnel costs decreased $0.7 million in 2021 as the Company scaled down certain research and development functions in the first quarter of 2020 as a result of certain programs being previously deprioritized. Selling, general and administrative expenses decreased $2.8 million, or 13%. Salaries, benefits, and other personnel costs decreased $1.0 million in 2021 primarily due to a reduced headcount as the Company scaled down its corporate functions to support its more streamlined organization and reduced stock compensation costs for previously granted awards that became fully vested in early 2021. Professional fees decreased $1.0 million primarily due to a decrease in legal fees associated with certain litigation matters that were settled in the second half of 2020. Net loss from continuing operations was $21.8 million, or $(0.11) per basic share, of which $9.7 million was for non-cash charges in 2021 compared to net loss from continuing operations of $20.8 million, or $(0.13) per basic share, of which $7.7 million was for non-cash charges in 2020.

Total revenues decreased $5.3 million, or 18%, from the quarter ended March 31, 2020. Collaboration and licensing revenues decreased $10.7 million primarily due to the recognition of previously deferred revenue upon the mutual termination of one of its collaboration agreements in February 2020. Product and service revenues generated by Trans Ova and Exemplar increased $5.4 million primarily due to higher customer demand for Trans Ova’s products and services as a result of stronger beef and dairy industries in the current year, as well as increased services provided by Exemplar to new and existing customers. Gross margin on products and services improved as a result of the increased revenues, a change in pricing structure for certain customers, and operational efficiencies that have been gained through reductions in workforce and improved inventory management.

On May 10, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the U.S. Food and Drug Administration ("FDA") has accepted the Company’s Investigational New Drug ("IND") application to initiate a Phase 1/2 multicenter study to assess the safety, tolerability and efficacy of MB-106, a CD20-targeted CAR T therapy for relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma ("B-NHL") and chronic lymphocytic leukemia ("CLL") (Press release, Mustang Bio, MAY 10, 2021, View Source [SID1234579603]).

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MB-106 targets CD20, a commercially validated target on the surface of cancer cells that has lacked a strong CAR T-based clinical focus in the U.S. MB-106 cells express a third-generation CAR derived from a fully human antibody that originated in the Fred Hutchinson Cancer Research Center ("Fred Hutch") laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division. The CAR T therapy was exclusively licensed to Mustang in 2017, and Fred Hutch and Mustang collaborated to develop the cell processing that will be used in the Mustang IND Phase 1/2 clinical trial.

To date, the same vector planned for use in the manufacturing of MB-106 is currently being evaluated in the ongoing Phase 1/2 study sponsored by Fred Hutch, where Mazyar Shadman, M.D., M.P.H., Associate Professor in the Clinical Research Division, is the Principal investigator. Data from this ongoing study were presented by Dr. Shadman at the 62nd Annual American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in 2020 and demonstrated a favorable safety profile, with an 89% overall response rate (ORR; 8/9 patients) and a 44% complete response rate (CR; 4/9 patients).

NHL is one of the most common cancers in the United States, accounting for about 4% of all cancers, and CLL accounts for about one-third of the new cases of leukemia. The American Cancer Society estimates that in the U.S. in 2021 about 81,560 people will be diagnosed NHL and 21,250 with CLL.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are pleased with the FDA’s acceptance of our IND application for MB-106, which allows us to further advance this CAR T therapy as a potentially safe and effective treatment option for B-NHL and CLL. It is especially gratifying that we were able to achieve this milestone in just 28 days after our IND submission. We are committed to finding better treatment options for patients living with these cancers and look forward to initiating our multicenter, Phase 1/2 clinical trial later this year, with Dr. Shadman as the Study Chair."

On May 10, 2021 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a synthetic lethality-focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that dose expansion of the ongoing Phase 1/2 study (ClinicalTrials.gov Identifier: NCT03947385) evaluating the combination of darovasertib and crizotinib in metastatic uveal melanoma (MUM) (Press release, Ideaya Biosciences, MAY 10, 2021, https://www.prnewswire.com/news-releases/ideaya-announces-dose-expansion-in-phase-12-study-of-darovasertib-and-crizotinib-combination-based-on-early-clinical-efficacy-in-first-combination-cohort-301287055.html [SID1234579624]). IDEAYA is the sponsor of this combination study, which is being conducted pursuant to a clinical trial collaboration and supply agreement with Pfizer Inc. Darovasertib is IDEAYA’s clinical stage protein kinase C, or PKC, inhibitor and crizotinib is a cMET inhibitor to which Pfizer has exclusive worldwide rights.

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"We are encouraged to see the early deep partial response in the first cohort of the darovasertib and crizotinib combination. We look forward to the dose expansion phase and to continue dose exploration to clinically validate the preclinical combination hypothesis discovered by IDEAYA," said Dr. Marlana Orloff, M.D., Assistant Professor, Thomas Jefferson University Hospitals.

IDEAYA presented translational data at AACR (Free AACR Whitepaper) 2021 retrospectively evaluating cMET expression in clinical biopsies from MUM patients in a Darovasertib Phase 1 clinical trial, as well as preclinical data evaluating synergy between darovasertib and crizotinib in relevant cell models of a liver tumor microenvironment, a site of approximately 90% of uveal melanoma metastases. "We identified inhibition of the cMET signaling pathway in combination with PKC in the metastatic setting as a potential treatment regimen, and are excited to observe our first signal of clinical activity to validate this research finding," said Mick O’Quigley, Vice President, Head of Development Operations at IDEAYA Biosciences.

Darovasertib / Crizotinib Combination Therapy

IDEAYA is continuing patient enrollment into the darovasertib / crizotinib combination arm under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

6 MUM patients have enrolled in the darovasertib and crizotinib combination study and 2 of these patients were evaluable for response with at least one post-baseline scan
Observed early clinical efficacy of the darovasertib and crizotinib combination in MUM. As of data and analyses cutoff on May 5, 2021 based on preliminary data from an unlocked database, these data showed:
tumor reduction in 2 of 2 evaluable patients in a first cohort
one unconfirmed partial response in a 3rd-line patient, with a 54% tumor reduction, which is the deepest response reported in the darovasertib clinical trial to date; this patient is awaiting a confirmatory scan
Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of May 5, 2021, based on preliminary data from an unlocked database, primarily include: serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing; and adverse events that occurred in at least two of the six treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, and syncope
Initiated dose expansion for a cohort of the Phase 1/2 darovasertib / crizotinib combination arm, with additional dose exploration ongoing
Observed preclinical synergies between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases, as reported at AACR (Free AACR Whitepaper) 2021
Correlated cMET expression and activation to observed clinical response based on a retrospective analysis of human clinical biopsies from the Novartis darovasertib Phase 1 clinical trial, supporting co-targeting PKC and cMET signaling

On May 10, 2021 Chugai Pharmaceutical Co., Ltd. (Head office: Tokyo; President & CEO: Osamu Okuda; "Chugai") and SBI Pharmaceuticals Co., Ltd. (Head office: Tokyo; Representative Director & President: Yoshitaka Kitao; "SBI Pharma") reported that the companies decided to terminate the license agreement for the photodynamic diagnostic agent "ALAGLIO Divided Granules 1.5g ("ALAGLIO")" and that Chugai will consequently discontinue marketing of the product (Press release, Chugai, MAY 10, 2021, View Source [SID1234579497]).

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Both companies entered into a license agreement for ALAGLIO on March 13, 2017 which granted Chugai exclusive marketing rights of ALAGLIO in Japan. SBI Pharma obtained regulatory approval for ALAGLIO on September 27, 2017 for the indication of diagnostic agent to visualize non-muscle invasive bladder cancer at the operation of its transurethral resection, and Chugai launched the product on December 19 after the product had been listed on the National Health Insurance reimbursement price list on November 22.

Chugai will discontinue marketing and information provision for ALAGLIO on May 31, 2021. SBI Pharma will announce how these activities will be conducted from June 1, 2021.

Chugai and SBI Pharma will corporate to accomplish a smooth transition and maintain promotion of proper use of the product during the transition period.

Trademarks used or mentioned in this release are protected by law.

On May 10, 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 its first quarter 2021 financial results, and provided recent corporate and program highlights (Press release, Aeglea BioTherapeutics, MAY 10, 2021, View Source [SID1234579541]).

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"We’ve had a strong start to 2021 and I am excited to see the significant momentum we have built for our pegzilarginase program from a clinical perspective as well as strengthening our commercial foundation in preparation for a potential FDA approval and launch. In just the last two months, we completed patient randomization for PEACE, secured a commercialization partner for pegzilarginase in Europe and the Middle East and launched THINK ARGININE, an Arginase 1 Deficiency disease education and diagnostic testing initiative in the United States," said Anthony Quinn, M.B Ch.B, Ph.D., president and chief executive officer of Aeglea. "This substantial progress sets us up well for the rest of 2021. We expect to provide topline data from the PEACE study in the fourth quarter, continue progressing our commercial strategy for pegzilarginase and advance our AGLE-177 clinical program in Homocystinuria. These accomplishments are critical milestones as we move closer to our mission of bringing impactful therapies to patients with rare metabolic disorders who currently have limited treatment options."

Recent Highlights and Updates

Corporate

In March, Aeglea announced it has entered into a license and supply agreement with Immedica Pharma AB granting Immedica exclusive commercialization rights in Europe and several Middle Eastern countries. Aeglea will receive an upfront payment of $21.5 million and is eligible for commercial and regulatory milestones of up to approximately $130 million and mid-twenties percentage royalties on net sales.
Pegzilarginase in Arginase 1 Deficiency

In April, the Company completed patient screening and randomization for PEACE, its pivotal Phase 3 clinical trial. Trial enrollment of 32 patients exceeded the target of 30 patients, underscoring the high levels of interest seen from patients, caregivers and investigators. Topline data are expected in the fourth quarter of 2021.
In May, we announced the launch of THINK ARGININE, a disease education initiative to improve the awareness and diagnosis of Arginase 1 Deficiency (ARG1-D). The initiative consists of a comprehensive healthcare provider education campaign and a no-charge diagnostic testing program for adults and children with suspected ARG1-D in the United States.
The no-charge diagnostic testing program includes amino acid testing working with Mayo Clinic Laboratories and genetic testing partnered with Invitae.
Upcoming Events

Aeglea will participate in the upcoming virtual conferences and events:

ISPOR 2021, May 17-20
Virtual Rare Disease Week on Capitol Hill 2021, July 14-22
First Quarter 2021 Financial Results

As of March 31, 2021, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $128.5 million, which excludes the upfront license receivable from Immedica for $21.5 million. Based on Aeglea’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2023.

Research and development expenses totaled $11.9 million for the first quarter of 2021 and $14.6 million for the first quarter of 2020. The decrease was primarily associated with completing certain pre-commercial manufacturing activities for Aeglea’s lead product candidate, pegzilarginase.

General and administrative expenses totaled $6.4 million for the first quarter of 2021 and $4.5 million for the first quarter of 2020. This increase was primarily due to ramping-up the Company’s commercial capabilities and infrastructure.

Net loss totaled $18.2 million and $18.7 million for the first quarter of 2021 and 2020, respectively, with non-cash stock compensation expense of $1.8 million and $1.3 million for the first 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 patients with 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. 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 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, 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 homocystine dimer. Aeglea is developing AGLE-177 for the treatment of patients with cystathionine beta synthase (CBS) deficiency, also known as 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 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received U.S. Rare Pediatric Disease and Orphan Drug Designations as well as EU Orphan Drug Designation. Aeglea initiated a Phase 1/2 trial in 2020 and continues patient identification and administrative activities.