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.

On May 10, 2021 Pliant Therapeutics, Inc. (Nasdaq: PLRX) ("the Company"), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, reported a corporate update and reported first quarter 2021 financial results (Press release, Pliant Therapeutics, MAY 10, 2021, View Source [SID1234579585]).

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"During the first quarter, we continued the strong momentum of advancing our broad and novel clinical and development-stage portfolio," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics. "With this progress and a financial runway taking us into 2023, we are well positioned to advance toward our objective of bringing potentially transformative treatments to patients in need."

First Quarter and Recent Highlights

PLN-74809 Phase 2a positron emission tomography (PET) imaging trial preliminary data expected in the first half 2021. This open-label, dose ranging trial is evaluating target receptor occupancy levels of PLN-74809 in the lungs of IPF patients across multiple single-dose cohorts utilizing a PET tracer of the integrin αvβ6. The goal of the trial is to confirm the ability of PLN-74809, a dual selective inhibitor of αvβ6/αvβ1, to penetrate highly fibrotic areas of the lung where αvβ6 expression is highest and bind to its target receptor. Additionally, the trial will establish a pharmacokinetic/ pharmacodynamic (PK/PD) relationship between PLN-74809 plasma exposure and αvβ6 receptor occupancy, allowing us to build a PK/PD model that will inform dose selection in later stage trials.

PLN-74809 Phase 2a INTEGRIS trial in idiopathic pulmonary fibrosis (IPF) continued to build momentum, currently on track to complete enrollment by the end of 2021. The primary endpoints of this 12-week randomized, dose-ranging, double-blind, placebo-controlled trial are the evaluation of PLN-74809’s safety, tolerability, and pharmacokinetics in IPF patients. The Company will also evaluate exploratory efficacy endpoints including Quantitative Lung Fibrosis, or QLF, imaging as well as pulmonary function tests.

PLN-74809 Phase 2a INTEGRIS trial in primary sclerosing cholangitis (PSC) continued to advance, currently on track to complete enrollment in the first half 2022. The primary endpoints of this 12-week randomized, dose-ranging, double-blind, placebo-controlled trial are the evaluation of PLN-74809’s safety, tolerability, and pharmacokinetics in PSC patients. The Company will also evaluate exploratory efficacy endpoints including fibrosis biomarkers such as Pro-C3 and ELF, changes in ALP, and liver imaging.

Successful completion of PLN-1474 Phase 1 trial and transfer of PLN-1474 to Novartis. The Phase 1 trial of PLN-1474 was a safety, tolerability, and pharmacokinetics dose-escalating first-in-human trial that enrolled 84 healthy volunteers. PLN-1474 was rapidly absorbed and well tolerated with no dose-or treatment-limiting toxicities or severe/ serious adverse events observed. In preclinical studies, PLN-1474 was observed to selectively block the αvβ1 integrin-mediated activation of TGF-β, reducing liver fibrosis in animal models. Following the successful completion of this study, PLN-1474 has been transferred to Novartis.
COVID-19 Preparedness

The Company continues to develop and maintain policies and procedures to enable us to operate safely and productively during the COVID-19 pandemic. The Company has experienced delays in clinical trial operations which have impacted and may further impact the expected timing of data readouts. The Company continues to work closely with clinical sites to continue site initiation and operation activities in compliance with study protocols while observing government and institutional guidelines.

First Quarter 2021 Financial Results

Research and development expenses were $18.5 million, as compared to $13.9 million for the prior-year quarter. The increase was due primarily to employee related expenses and higher costs related to the advancement of several programs and ongoing Phase 1/2 clinical trials.
General and administrative expenses were $6.6 million, as compared to $4.0 million for the prior-year quarter. The increase was due to higher personnel-related and professional services expenses.
Net loss of $22.9 million as compared to a net income of $11.0 million for the prior-year quarter due to a decrease in related party revenue driven by the achievement of a first-patient-first-dose milestone in the first quarter of 2020 for the PLN-1474 Phase 1 trial.
As of March 31, 2021, the Company had cash, cash equivalents and short-term investments of $264.1 million. The Company believes it has sufficient funds to meet its operating and capital requirements into 2023.