On May 16, 2022 Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, reported financial results for the first quarter ending March 31, 2022, early clinical observations from its MGTA-117 clinical trial and other recent program highlights (Press release, Magenta Therapeutics, MAY 16, 2022, View Source [SID1234614660]).

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"We are pleased with the progress of our MGTA-117 Phase 1/2 clinical trial. Our clinical observations from preliminary data indicate that MGTA-117 is functioning as designed by binding to the intended cells with a post-dose reduction of target cells in the bone marrow, clearing the body rapidly and doing so with a favorable tolerability profile. With this level of measurable activity at our lowest dose, we believe we will collect enough information in 2022 from the next 1-2 cohorts to build a data set for communications with regulators for our planned transition to the transplant-eligible AML patient population. In light of the turbulence in the capital markets, we are also pleased to have a strong cash position and a projected lower quarterly spending rate which we believe will allow us to reach our critical value inflection points, including possible proof-of-concept of MGTA-117 in transplant-eligible AML patients and genetic diseases with gene therapy," said Jason Gardner, President and Chief Executive Officer of Magenta Therapeutics.

Program Highlights:

MGTA-117 Phase 1/2 Clinical Trial Ongoing

Clinical Trial Design and Objectives. Magenta is conducting a Phase 1/2 dose-escalation clinical trial of MGTA-117 in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB).

Clinical Trial Status and Scope of Early Clinical Observations. The clinical trial has progressed from Cohort 1 to Cohort 2 after meeting all protocol requirements for dose escalation. Patients in Cohort 1, as expected, had varying degrees of disease burden as measured in part by the percentage of leukemic cells in the bone marrow and the bloodstream. Clinical observations were made from a preliminary data set from Cohort 1 which utilizes the trial’s lowest dose of MGTA-117 (0.02 mg/kg). Three patients with relapsed/refractory AML completed the safety evaluation period. A fourth patient with high disease burden did not complete the evaluation period due to disease progression with no drug-related adverse events. Cohort 2 is now open and enrolling and MGTA-117 will be evaluated as a single dose of 0.04 mg/kg.
Early Clinical Observations from Cohort 1.
Target Engagement/Binding: Preliminary data from four patients were available for measuring target engagement. In all patients, MGTA-117 was shown to bind CD117+ cells in the blood as measured by a receptor occupancy assay.
Cell Depletion: Bone marrow aspirates were obtained for three patients at baseline and post-dosing and provided evidence supportive of biologic activity.
Reductions of Erythroid Progenitor Cells in the Bone Marrow: One patient had measurable reductions of CD117+ erythroid progenitor cells in the bone marrow following MGTA-117 administration.
Reductions of Blasts in the Bone Marrow: An additional patient had an approximate 83% reduction of blasts in the bone marrow at day 14 post-dosing (from 6% to 1%). The patient proceeded to a conditioning regimen followed by stem cell transplant. The patient’s baseline profile closely resembled that of transplant-eligible AML patients due to relatively low percentages of blasts in the bone marrow and bloodstream. Magenta believes that this outcome provides an encouraging early signal in support of MGTA-117’s planned transition to the transplant-eligible AML patient population.
Rapid Drug Clearance: Preliminary data from four patients were available for measuring drug clearance. In all patients, MGTA-117 was deemed to be cleared 48 hours after dosing. Rapid and sufficient clearance of conditioning agents from circulation is a necessary step before stem cell infusion.
Favorable Tolerability Profile: For all four patients, no unexpected or serious drug-related adverse events were reported, no dose-limiting toxicities were observed and no drug-related adverse events higher than Grade 1 were reported.
"We are encouraged by these preliminary data. Post-dose reduction of progenitor and tumor blast cell populations in bone marrow suggests biologic activity. We anticipate that dose escalation will lead to further drug activity and enable identification of an appropriate dose for development in patients eligible for transplant," said Dr. Jeff Humphrey, Chief Medical Officer of Magenta Therapeutics.

MGTA-117 Clinical Data Disclosure Expectations in 2022. Magenta expects to report additional progress updates and clinical observations from multiple dose-escalation cohorts in 2022, including providing patient-level data from this clinical trial at a scientific congress later this year.
Plans to Transition to Transplant-Eligible Patients. The company anticipates that further data from the current clinical trial showing MGTA-117 at high receptor occupancy levels with well-tolerated cell depletion in the blood and/or bone marrow will be supportive of the planned transition to transplant-eligible patients. Magenta is planning to engage with regulatory authorities prior to amending the clinical trial protocol to evaluate MGTA-117 as a targeted conditioning agent in combination with reduced intensity chemotherapy prior to a stem cell transplant. Simultaneously with the planned clinical trial transition, Magenta expects to initiate clinical collaboration planning with existing and potential gene therapy partners to explore MGTA-117 as a single agent conditioning regimen prior to autologous stem cell gene therapy.
CD45-Antibody Drug Conjugate (ADC): Second Targeted Conditioning Program

CD45 is broadly expressed on hematopoietic cells and Magenta’s CD45-ADC is designed to selectively target and deplete both stem cells and lymphocytes, which would enable patients with blood cancers and autoimmune diseases to avoid the use of chemotherapy prior to stem cell transplant.

Magenta has initiated IND-enabling studies with data from a key dose-ranging toxicology study expected in the second half of 2022.
MGTA-145 Stem Cell Mobilization and Collection

Magenta is developing MGTA-145, in combination with plerixafor, to improve stem cell mobilization from bone marrow into the bloodstream. Collection of peripheral blood stem cells, known as stem cell mobilization, is a common source of stem cells for hematopoietic stem cell transplants and gene therapy applications.

Magenta is preparing for the initiation of a Phase 2 clinical trial in sickle cell disease (SCD) in collaboration with bluebird bio to evaluate MGTA-145, in combination with plerixafor, for mobilization and collection of stem cells in patients with sickle cell disease. Mobilization and collection are difficult in sickle cell disease, and there is a clear unmet medical need. Initial data from this trial are expected in the second half of 2022.
Financial Results:

Cash Position: Cash, cash equivalents and marketable securities as of March 31, 2022, were $156.6 million, compared to $176.9 million as of December 31, 2021. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund its current operational plan into the second quarter of 2024.

Research and Development Expenses: Research and development expenses were $16.5 million in the first quarter of 2022, compared to $11.7 million in the first quarter of 2021. The increase was driven primarily by the achievement of a development milestone under Magenta’s license agreement related to MGTA-117, an increase in preclinical and manufacturing costs to support our CD45-ADC IND enabling studies, offset by a decrease in costs related to MGTA-456 which was discontinued. The increase was also due to an increase in research and development headcount.

General and Administrative Expenses: General and administrative expenses were $7.3 million for the first quarter of 2022, compared to $7.0 million for the first quarter of 2021.

Net Loss: Net loss was $23.0 million for the first quarter of 2022, compared to net loss of $17.5 million for the first quarter of 2021.

On May 16, 2022 CEL-SCI Corporation (NYSE American: CVM) reported financial results for the quarter ended March 31, 2022, as well as key clinical and corporate developments (Press release, Cel-Sci, MAY 16, 2022, View Source [SID1234614676]).

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Clinical and Corporate Developments include:

The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) has accepted two abstracts related to CEL-SCI’s pivotal Phase 3 Multikine (Leukocyte Interleukin, Injection)* head and neck cancer clinical trial for presentation at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting to be held June 3-7, 2022 in Chicago, Illinois. The abstract titles are:
"Novel algorithm for assigning risk/disease-directed treatment (DDT) choice in locally advanced primary squamous cell carcinoma of the head and neck (SCCHN): Using pretreatment data only."
"Leukocyte interleukin injection (LI) immunotherapy extends overall survival (OS) in treatment-naive low-risk (LR) locally advanced primary squamous cell carcinoma of the head and neck: The IT-MATTERS study."
Head and neck cancer patients who are scheduled to receive surgery and radiation as their first treatments have not seen a marked improvement in their treatment outcome in decades. CEL-SCI’s Phase 3 study showed great improvement in survival with no toxicity issues for these patients with a statistically significant, robust, and durable survival benefit of 14.1% at 5 years. This is clearly an unmet medical need for an estimated 211,000 people globally.
Additional results from the Phase 3 study of Multikine in advanced primary head and neck cancer have been submitted to the U.S. government clinical trial website www.clinicaltrials.gov. That data is expected to be released to the public in the near future.
CEL-SCI’s dedicated current Good Manufacturing Practice (cGMP) facility in which it manufactures Multikine is now undergoing validation following the completion of its commercial scale build out during the first quarter of 2022. The construction is designed to ensure the facility will be compliant with all U.S. Food and Drug Administration’s (FDA) and European cGMP regulations.
As of March 31, 2022, CEL-SCI had $34.3 million in cash and cash equivalents.
"ASCO’s annual meeting in June, with over 40,000 oncology professionals from over 100 countries expected, is one of the largest and most prominent oncology conferences. Our scientific team looks forward to presenting two abstracts there, and we expect a high level of interest based on Multikine’s results and the fact that outcomes have not improved for the head and neck cancer population in decades," stated CEL-SCI CEO, Geert Kersten. "The conference is well timed to inform oncologists from around the world about Multikine ahead of our planned regulatory filing for approval."

CEL-SCI reported an operating loss of $18.4 million for the six months ended March 31, 2022 versus an operating loss of $17.3 million for the six months ended March 31, 2021. CEL-SCI reported an operating loss of $9.6 million for the three months ended March 31, 2022 versus an operating loss of $8.5 million for the three months ended March 31, 2021. Net cash used in operating activities was $7.5 million for the six months ended March 31, 2022 which represents a decrease of $1.2 million compared to the six months ended March 31, 2021.

On May 16, 2022 Scandion Oncology (Scandion) reported that will publish its Q1 2022 interim report on Thursday, May 19, 2022 before 09:00 CET (Press release, Scandion Oncology, MAY 16, 2022, View Source;2022,c3567316 [SID1234614574]).

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Scandion Oncology’s Executive Management will host a webcast and conference call the same day at 10:00 CET presenting the results and a company update.

At the end of the presentation there will be a Q&A session.

The information was provided by the contact person above for publication on May 16, 2022, at 08.30 CET.

On May 16, 2022 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported that the first patient has been dosed in its Phase 1/2 clinical trial of CFT8634, an orally bioavailable BiDAC degrader targeting BRD9 for the treatment of SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors (Press release, C4 Therapeutics, MAY 16, 2022, View Source [SID1234614645]).

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"The initiation of our first clinical trial of CFT8634 is a significant milestone for C4 Therapeutics as we apply our TORPEDO platform to an oncology target currently considered ‘undruggable’ and work to provide a new treatment option for patients living with synovial sarcoma and SMARCB1-null tumors," said Adam Crystal, M.D., Ph.D., chief medical officer of C4 Therapeutics. "Based on our pre-clinical research showing that the BRD9 degrader CFT8634 is potent, selective and efficacious in models of synovial sarcoma and malignant rhabdoid tumors, we believe CFT8634 may offer an effective targeted treatment for patients who currently have limited therapeutic options."

The Phase 1/2 trial will primarily investigate safety, tolerability and anti-tumor activity with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT8634. The Phase 1 portion of the study will evaluate CFT8634 as an oral, single agent therapy for patients with synovial sarcoma and SMARCB1-null tumors to identify a recommended Phase 2 dose. Following identification of recommended dosage, the Phase 2 portion of the trial is expected to expand to the following investigational arms: one in synovial sarcoma, and one in SMARCB1-null tumors. Across the Phase 1/2 trial, C4T plans to enroll approximately 90 patients.

CFT8634 is C4T’s second oncology program to enter clinical studies from its internally developed research pipeline. CFT8634 is C4T’s first BiDAC degrader candidate to be evaluated in the clinic.

To learn more about the CFT8634 clinical trial, visit clinicaltrials.gov (identifier: NCT 05355753).

About CFT8634
CFT8634 is a BiDAC degrader targeting BRD9 for the treatment of cancers that are dependent on BRD9, including synovial sarcoma and SMARCB1-null cancers. BRD9 has been considered an "undruggable" target due to the inability of bromodomain inhibitors to effectively treat these cancers. Unlike BRD9 inhibition, BRD9 degradation has been shown to be efficacious in pre-clinical models of synovial sarcoma. By leveraging C4T’s TORPEDO platform, C4T developed CFT8634, an orally bioavailable, selective degrader of BRD9. In March 2022, C4T announced

the U.S. Food and Drug Administration had granted orphan drug designation (ODD) to CFT8634.

About Synovial Sarcoma and SMARCB1-null Tumors
Synovial sarcoma is a rare and aggressive subtype of soft tissue sarcoma. It accounts for approximately 10 percent of all sarcoma diagnoses. An estimated 900 people are diagnosed with synovial sarcoma in the U.S. each year. Approximately one-third of patients are diagnosed under the age of 30.

SMARCB1-null tumors include malignant rhabdoid tumor, poorly differentiated chordoma, epithelioid sarcoma and other rare cancers; some subtypes are most commonly diagnosed in children and young adults.

Both synovial sarcoma and SMARCB1-null tumors are believed to be dependent on BRD9 and, as a result, CFT8634 may be an effective treatment.

On May 16, 2022 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported a clinical trial collaboration and supply agreement with Merck (known as MSD outside the US and Canada) (Press release, Athenex, MAY 16, 2022, View Source [SID1234614661]). The agreement applies to the expansion phase of the Phase 1 clinical trial evaluating Athenex’s oral paclitaxel in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for certain NSCLC patients.

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The agreement will support the expansion phase of the trial to further investigate the preliminary encouraging results of the KX-ORAX-011 Phase 1 clinical trial evaluating Oraxol (encequidar plus oral paclitaxel) in combination with pembrolizumab for certain NSCLC patients. The two companies will form a Joint Development Committee to review the clinical trial results.

"We are keen to collaborate with Merck to further investigate the therapeutic potential of Oraxol plus KEYTRUDA in patients with NSCLC patients who progressed on previous anti-PD1/ anti-PD-L1 therapy or in combination with chemotherapy," said Dr. Rudolf Kwan, Chief Medical Officer of Athenex. "If the preliminary efficacy and safety data can be confirmed, it may lead to a new paradigm in the treatment of certain NSCLC patients."

KX-ORAX-011 is an ongoing Phase 1 trial evaluating Oraxol in combination with pembrolizumab in patients with advanced solid tumors. Following completion of the dose escalation phase, the expansion phase is currently evaluating the combination therapy in patients with NSCLC who progressed on previous anti-PD1/ anti-PD-L1 therapy or in combination with chemotherapy. The NSCLC expansion cohort is actively recruiting and aims to enroll approximately 50 patients.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Oral Paclitaxel
Athenex’s oral paclitaxel and encequidar ("oral paclitaxel") is in the earlier stages of development for solid malignancies. Encequidar, the cornerstone of Athenex’s Orascovery technology platform, is a highly specific and potent inhibitor of the transport protein called P-glycoprotein (P-gp) in the gastrointestinal (GI) tract. By localizing P-gp inhibitory activity in the GI tract, encequidar improves the absorption of chemotherapeutic agents while limiting the potential for unnecessary P-gp inhibition at other sites in the body. The potency, selectivity, and low absorption of encequidar enables the oral administration of IV chemotherapies.