On March 8, 2022 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported that it will report its fourth quarter and full year 2021 financial results on Tuesday, March 15, 2022 (Press release, Altimmune, MAR 8, 2022, View Source [SID1234609685]).

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Altimmune management will host a conference call at 8:30 am E.T. on March 15 to discuss financial results and provide a business update.

On March 8, 2022 Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, have data pointing to the limitations of Signatera, a popular liquid biopsy or blood draw test reported that is used to detect the recurrence of colorectal cancer in patients who have had their disease surgically removed (Press release, City of Hope, MAR 8, 2022, View Source [SID1234609701]). The study was published today in JAMA Open Network.

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"A liquid biopsy measuring circulating tumor DNA is a novel way to test for residual disease in patients who have recently received curative resection for colon cancer. Identifying early disease recurrence is important as it may allow for potential curative interventions," said Marwan Fakih, M.D., co-director of City of Hope’s Gastrointestinal Cancer Program and lead author of the new study.

City of Hope researchers evaluated 48 study participants who had had their colorectal cancer resected. The scientists sought to identify which technique might be superior in identifying residual disease and early cancer recurrence by comparing the use of Signatera’s circulating tumor DNA (ctDNA) analysis, which is often used to screen for colorectal cancer, to the standard-of-care recommended by the National Comprehensive Cancer Network (NCCN): X-rays via computed tomography (CT) scan and a carcinoembryonic antigen (CEA) test, which measures a tumor marker via a blood draw.

Fifteen patients experienced colorectal cancer recurrence. Within this group, standard-of-care surveillance was better at identifying early disease. For example, Signatera did not identify patients who had early recurrence in the lungs. Three patients received a negative ctDNA test, but standard-of-care surveillance techniques identified disease recurrence in their lungs.

"Imaging remains the most important surveillance assay in the follow-up of resected colorectal cancers. Clinicians should continue to abide by NCCN guidelines. For those who decide to implement ctDNA into their surveillance algorithm, they should be aware of the limitations associated with this assay," Fakih said, referencing current clinical trials elsewhere where clinicians are de-intensifying chemotherapy based on a negative ctDNA test by Signatera.

It may be premature to base treatment decisions solely on ctDNA results "given the limitations of Singatera sensitivity," said Fakih, the Judy & Bernard Briskin Distinguished Director of Clinical Research and a professor in City of Hope’s Department of Medical Oncology & Therapeutics Research.

Fakih added that using liquid biopsies to identify disease recurrence is an attractive, noninvasive option. Liquid biopsy is convenient and, unlike CT, does not expose patients to low doses of radiation. However, scientists are still working to develop a reliable and sensitive liquid biopsy to detect colorectal cancer recurrence. Nevertheless, there is promise.

"ctDNA was able to identify several recurrences in the liver and lymph nodes ahead of imaging," Fakih said. "For now, ctDNA can be considered, if any at all, as a complement to the standard approach recommended by the NCCN, but one must be cognizant of its limitations."

JAMA Network Open published the study under the title, "Evaluation of comparative surveillance strategies of circulating tumor DNA, imaging and carcinoembryonic antigen levels in patients with resected colorectal cancer."

On March 8, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that new preclinical data on its small-molecule Wee1 inhibitors will be presented during a poster session at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in New Orleans, Louisiana, April 8-13, 2022 (Press release, Schrodinger, MAR 8, 2022, View Source [SID1234609719]).

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Wee1 is a gatekeeper checkpoint kinase that prevents cellular progression through the cell cycle, allowing time for DNA repair before cell division takes place. Inhibition of Wee1 allows for accumulation of DNA damage, triggering DNA breakage and apoptosis in tumor cells. Data from third party clinical studies are showing promising anti-tumor activity in solid tumors, including ovarian and uterine cancer. Schrödinger has identified multiple highly selective Wee1 inhibitors with optimized physicochemical properties that show strong pharmacodynamic responses and anti-tumor activity in preclinical models. This potentially best-in-class profile may position these structurally distinct Wee1 inhibitors for applications both as monotherapy and as combination therapy with other agents. Schrödinger expects to select a Wee1 development candidate later this year.

Details of the poster presentation are as follows:

Title: Discovery of potent, selective, and orally available Wee1 inhibitors that demonstrate increased DNA damage and mitosis in tumor cells leading to tumor regression in vivo
Abstract number: 2570
Date & time: Tuesday, April 12, 9:00 a.m – 12:30 p.m. CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 21

On March 8, 2022 Sharp HealthCare, in collaboration with Nascent Biotech, Inc, reported, its participation in a clinical trial for a novel investigational immunotherapy treatment for patients with glioblastoma (GBM), the deadliest form of brain cancer (Press release, Nascent Biotech, MAR 8, 2022, View Source [SID1234609737]).

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Pritumumab (PTB) is a unique monoclonal antibody that attacks cancers originating in the cells lining an organ – referred to as epithelial cells. These include cancers of the brain, breast, colon and pancreas, as well as melanoma. Prior Phase I and II clinical trials in Japan focused on the treatment of high-grade gliomas including GBM.

This Phase I clinical trial leverages Sharp HealthCare’s comprehensive cancer program in this collaboration when treating all forms of brain tumors. With more than 23,000 new cases of GBM diagnosed in the U.S. every year, Sharp HealthCare’s cancer expertise and reputation appealed to Nascent Biotech as they chose additional sites.

"The clinical trial is a good fit for Sharp HealthCare, which is devoted to compassionate patient-centered care, creative innovation, and clinical excellence," said Dr. Charles Redfern, medical director of neuro-oncology at Sharp HealthCare’s Laurel Amtower Cancer Institute and Neuro-Oncology Center, "This is an exciting clinical trial with targeted immunotherapy for patients with GBM."

Pritumumab works by targeting cell surface vimentin, a protein expressed on the surface of epithelial cancers. Because vimentin is found in a variety of cancers, the clinical trial at Sharp HealthCare could have implications for more common cancers, such as breast or lung. In fact, the trial will employ a unique Phase I design that can also be used in studies of brain metastases and leptomeningeal cancers arising from breast, lung and other solid tumors.

"There are significant unmet medical needs in a variety of cancers," said Sean Carrick, CEO of Nascent Biotech, makers of the immunotherapy treatment. "Nascent is committed to changing patient expectations and outcomes in one of the world’s most debilitating cancers and Sharp is a valuable partner towards achieving this goal. We’re highly encouraged by the potential of Pritumumab to deliver an innovative, first-in-class treatment option, and we are delighted to be working closely with the Laurel Amtower Cancer Institute and Neuro-Oncology Center at Sharp HealthCare for this study."

On March 8, 2022 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 fourth quarter and full year 2021, and provided program updates (Press release, Aeglea BioTherapeutics, MAR 8, 2022, View Source [SID1234609636]).

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"2021 moved us closer to our goal of delivering life-changing medicines to people with rare metabolic diseases with positive topline data from our pivotal Phase 3 trial of pegzilarginase for Arginase 1 Deficiency and the dosing of the first patients in our Phase 1/2 trial of AGLE-177 for Homocystinuria. We enter 2022 well positioned to capitalize on the momentum we’ve built," said Anthony Quinn, M.B., Ch.B., Ph. D., president and chief executive officer of Aeglea. "We are excited about the opportunities in 2022 for a transformative year. With a strong portfolio of human enzyme therapies for rare metabolic diseases, we are looking forward to advancing all our programs, including sharing clinical data from our AGLE-177 program, progressing AGLE-325 for Cystinuria through IND-enabling studies and working with the FDA throughout the regulatory process for pegzilarginase."

Program Updates

Pegzilarginase in Arginase 1 Deficiency

Announced the PEACE Phase 3 clinical trial met its primary endpoint with an 80% plasma arginine reduction, and an accompanying positive trend in a secondary endpoint assessing mobility. Additionally, 90.5% of patients achieved normal plasma arginine levels. Pegzilarginase was well-tolerated, and no patients discontinued the trial due to adverse events.
Highlighted 104-week data from the GMFM-E and 6-Minute Walk Test assessments from the Phase 1/2 open-label extension, which underscores the sustained, long-term impact of pegzilarginase treatment on mobility.
Plan to present additional data from PEACE Phase 3 clinical trial at the Society for Inherited Metabolic Disorders (SIMD) Annual Meeting in April 2022.
Hosted a Key Opinion Leader and Patient Caregiver event to provide insights and perspectives on treating and living with Arginase 1 Deficiency.
Met with U.S. Food and Drug Administration (FDA) in late February to discuss data from the pegzilarginase program and the path towards Biologic License Application (BLA) submission.
BLA preparation on track to enable a second quarter 2022 submission.
AGLE-177 in Homocystinuria

Completed dosing in the 0.15 mg/kg intravenous cohort in the Phase 1/2 clinical trial. AGLE-177 was well tolerated with no safety concerns and data from this first cohort showed reductions in total homocysteine in all patients.
The encouraging results from the first cohort allowed the Company to advance directly to the 0.45 mg/kg subcutaneous dose, accelerating the generation of dose response data. This second cohort is currently being dosed.
Filed an Investigational New Drug (IND) application with the FDA. Acceptance of the IND would allow the Company to open clinical trial sites in the U.S. for the Phase 1/2 clinical trial and a potential pivotal Phase 3 trial.
Expect to announce Phase 1/2 clinical data in the second half of 2022.
AGLE-325 in Cystinuria

Shared preclinical data from optimized clinical candidate, which the Company believes will support an attractive clinical dosing schedule.
Plan to move through IND-enabling studies in 2022.
Upcoming Events

American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, March 22-26
American Academy of Neurology Annual Conference, April 2-7
Society for Inherited Metabolic Disorders 43rd Annual Meeting, April 10-13
Needham Virtual Healthcare Conference, April 11-14
Fourth Quarter and Full Year 2021 Financial Results

As of December 31, 2021, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $95.0 million. The Company expects its cash, cash equivalents and investments will enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2023.

Aeglea recognized development fee revenues of $3.6 million in the fourth 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 (License and Supply Agreement). The revenues recorded in the fourth quarter of 2021 are related to the delivery of clinical trial and regulatory services. Aeglea recognized no revenue for the fourth quarter of 2020.

Aeglea recognized license and development fee revenues of $18.7 million in the year ended December 31, 2021, as a result of its License and Supply Agreement. The revenues recorded in the year ended December 31, 2021 are related to the transfer of the license and delivery of clinical trial and regulatory services. Aeglea recognized no revenue for the year ended December 31, 2020.

Research and development expenses totaled $16.8 million for the fourth quarter of 2021 and $15.8 million for the fourth quarter of 2020. The increase was primarily associated with a ramp-up in BLA development activities and increased enrollment in our PEACE Phase 3 trial of pegzilarginase for the treatment of patients with Arginase 1 Deficiency.

Research and development expenses totaled $57.1 million for the year ended December 31, 2021 and $59.6 million for the year ended December 31, 2020. The decrease was primarily associated with completing certain pre-commercial manufacturing activities for pegzilarginase and completing formulation, characterization, and stability studies for AGLE-177.

General and administrative expenses totaled $7.3 million for the fourth quarter of 2021 and $7.0 million for the fourth quarter of 2020. This increase was primarily due to changes in employee headcount and additional compensation to support the development of the Company’s commercial capabilities and infrastructure.

General and administrative expenses totaled $27.3 million for the year ended December 31, 2021 and $21.8 million for the year ended December 31, 2020. This increase was primarily due to changes in employee headcount and additional compensation and an increase in operational expenses to build the Company’s commercial capabilities and infrastructure.

Net loss totaled $20.4 million and $22.7 million for the fourth quarter of 2021 and 2020, respectively, with non-cash stock compensation expense of $2.1 million and $1.6 million for the fourth quarter of 2021 and 2020, respectively. Net loss totaled $65.8 million and $80.9 million for the years ended December 31, 2021 and 2020, respectively, with non-cash stock compensation expense of $8.0 million and $6.3 million for the years ended December 31, 2021 and 2020, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and 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.

In December 2021, Aeglea announced the PEACE Phase 3 clinical trial met its primary endpoint with an 80% plasma arginine reduction. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels. The arginine lowering was accompanied by a positive trend in a secondary endpoint, GMFM-E, which is a key clinical assessment of mobility. Aeglea’s Phase 1/2 and Phase 2 Open-Label Extension (OLE) data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug Designations from the U.S. Food and Drug Administration 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 is engineered to degrade the amino acid homocysteine and its 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 total homocysteine. 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 both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.