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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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).

On November 4, 2021 AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, reported it is extending its research partnership with leading scientists at the Center for Neurodegenerative Disease Research at the Perelman School of Medicine at the University of Pennsylvania (Penn) (Press release, AC Immune, NOV 4, 2021, View Source [SID1234594477]). The partnership is focused on studying the pathological mechanism of transactive response DNA binding protein 43 kDa (TDP-43) misfolding, aggregation and cell-to-cell transmission.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The successful first two years of the collaboration between AC Immune and Penn demonstrated that TDP-43 aggregates from the brains of donors with different TDP-43 proteinopathies have distinct seeding and spreading capacity in vivo. The proteinopathies studied included amyotrophic lateral sclerosis (ALS) and different subtypes of frontotemporal lobar degeneration-TDP (FTLD-TDP). These results confirm the existence of distinct pathogenic TDP-43 species and have been published in Neuropathology and Applied Neurobiology1.

In extending the collaboration with Penn, we aim to further understand the role of these distinct pathogenic TDP-43 species in the different TDP-43 proteinopathies. Through the development of novel experimental models, AC Immune and Penn hope to unravel the underlying mechanisms of cell-to-cell transmission of TDP-43 pathology that could provide new therapeutic strategies to target TDP-43-related proteinopathies.

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "We are very excited to extend our collaboration with the outstanding team of Professor Virginia Lee and Dr. Sílvia Porta at the University of Pennsylvania, continuing our exploration into the mechanisms and pathology driven by TDP-43. Our work has led to a better understanding of TDP-43 pathologies, which supports ACoImmune’s aim as we advance one of the industry’s broadest and most diversified pipeline with novel therapeutic and diagnostic approaches against neurodegenerative diseases."

Prof. Virginia M.Y. Lee, Director of the Center for Neurodegenerative Disease Research at the University of Pennsylvania, commented: "TDP-43 pathology is strongly associated with cognitive decline and episodic memory loss in neurodegenerative diseases, such as FTLD and ALS, and also plays an important role in Alzheimer’s disease. Our collaboration with AC Immune shows why industry sponsorship of academic research is vital for funding studies to advance our understanding into such an important target as TDP-43."

AC Immune has a lead anti-TDP-43 antibody in preclinical development, which has shown significantly reduced levels of pathological form of TDP-43 in the brain and conferred neuroprotection in murine neurodegenerative disease models. The company is also developing a first-in-class TDP-43 positron emission tomography (PET) tracer.

On November 4, 2021 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported dose administration for the first patient in a Phase 1 first-in-human study evaluating the safety and tolerability of MP0317, which targets both the fibroblast activation protein (FAP) and the immunostimulatory protein CD40 to enable tumor-localized immune activation (Press release, Molecular Partners, NOV 4, 2021, View Source [SID1234594476]). MP0317 is the second DARPin therapeutic candidate in the company’s immuno-oncology pipeline to enter clinical trials. Through this mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to other CD40-targeting agents.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The multispecificity afforded by DARPin technology allows us to design novel immuno-oncology candidates with additional control mechanisms for greater specificity and reduced systemic toxicity compared to monoclonal antibodies and other approaches," said Nicolas Leupin, M.D., Ph.D., Chief Medical Officer of Molecular Partners. "Having previously demonstrated the ability of FAP-dependent tumor-localized immune engagement in our MP0310 program, we are excited to see how this mechanism translates to patient benefit in our second immuno-oncology program. MP0317 represents another step in the evolution of our DARPin platform to deliver increasingly sophisticated candidates that can potentially direct immune attack to the right cells, at the right place, and at the right time."

Preclinical data from MP0317 in human tumor samples show that it activates B-cells, dendritic cells and macrophages, and induces a broad range of pro-inflammatory activities, including macrophage repolarization and reversion of T‑cell suppression. The multispecific design of MP0317 is expected to ensure that activation of CD40 will only occur in the presence of FAP, which is highly expressed in the connective tissue of a broad range of solid tumors. As previously presented1, the anti-tumor effect induced by MP0317 was comparable to that achieved by an anti-CD40 antibody. The Company believes these data support MP0317’s potential to deliver tumor-localized CD40-mediated immune cell activation while avoiding the systemic toxicity seen with other CD40-targeting agents.

The open-label dose escalation study announced today is designed to assess the safety and tolerability as well as pharmacokinetics and pharmacodynamics of MP0317 as a monotherapy in patients with solid tumors known to express FAP and CD40. Enrollment will take place in the Netherlands and France. Up to 30 patients are expected to be enrolled across six dosing cohorts and up to 15 patients dosed in a dose expansion cohort. Patients will be dosed every three weeks. In addition to evaluating monotherapy dynamics, the study will gather a wide variety of biomarker data to support the establishment of combination therapies with MP0317 in specific indications.

About Molecular Partners’ Immuno-oncology Product Candidates
Molecular Partners is developing several candidates designed to activate the immune system to fight cancer while reducing damage to healthy cells. These candidates use multiple novel DARPin technologies potentially applicable against a wide range of tumor types, including DARPin candidates with the ability to restrict immune activation to the tumor microenvironment, the ability to target intracellular disease-associated proteins, and multiple novel control mechanisms for immune activation designed to direct immune attack to the right cells, at the right place, and at the right time. These capabilities can be combined during candidate design through the inherent modularity of the DARPin platform, to provide precise control over immune activation and potentially enable more effective cancer immunotherapies.

On November 4, 2021 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that MediciNova’s collaborator, Dr. Justin Lathia, Co-Director of the Brain Tumor Research and Therapeutic Development Center of Excellence at Cleveland Clinic Lerner Research Institute, and Professor, Department of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, will present new data regarding MN-166 (ibudilast) from a glioblastoma animal model study at the 26th Annual Meeting of the Society for Neuro-Oncology (SNO) to be held November 18 – 21, 2021 in Boston (Press release, MediciNova, NOV 4, 2021, View Source [SID1234594475]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation details are as follows:
Date: Saturday November 20, 2021
Session Title: Concurrent Session: Microglia/Macrophages and Gliomas
Session Time: 10:45 AM – 12:15 PM
Presentation Title: Sexually Dimorphic Myeloid Cells Drive Glioblastoma
Presentation Time: 11:50 AM – 12:10 PM

About MN-166 (ibudilast)

MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases including ALS, progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) is being evaluated in patients at risk for developing acute respiratory distress syndrome (ARDS).