On August 6, 2022 AstraZeneca and Daiichi Sankyo reported that it’s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy (Press release, AstraZeneca, AUG 6, 2022, View Source [SID1234617720]).

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Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The approval by the Food and Drug Administration (FDA) was based on the results from the DESTINY-Breast04 Phase III trial. In the trial, Enhertu reduced the risk of disease progression or death by 50% versus physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer with hormone receptor (HR)-positive disease or HR-negative disease (median progression-free survival [PFS] 9.9 versus 5.1 months; hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.40-0.63; p<0.0001). A median overall survival (OS) of 23.4 months was seen in patients treated with Enhertu versus 16.8 months in those treated with chemotherapy, a 36% reduction in the risk of death (HR 0.64; 95% CI 0.49-0.84; p=0.001).

Shanu Modi, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, US, said: "Approximately half of all patients with breast cancer have tumours that are HER2-low, which have previously been classified as HER2-negative and have not had effective treatment options with HER2-targeted medicines. Based on the promising results of the DESTINY-Breast04 trial, clinicians are starting to differentiate levels of HER2 expression and redefine how metastatic breast cancer is classified with a distinct HER2-low patient population that may be eligible for trastuzumab deruxtecan."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "The rapid approval of Enhertu in HER2-low metastatic breast cancer by the FDA underscores the urgency to bring this transformational medicine to patients as quickly as possible. Patients with HER2-low tumours, who are identified through existing HER2 testing methods, will now have the opportunity to be treated based upon their HER2 status."

Ken Keller, Global Head of Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: "Today’s FDA approval marks a monumental moment in breast cancer treatment as Enhertu is the first-ever HER2-directed medicine to be approved for the treatment of patients with HER2-low metastatic breast cancer. With the ground-breaking survival benefit seen in the DESTINY-Breast04 trial, this milestone confirms the importance of targeting lower levels of HER2 expression in the treatment of metastatic breast cancer and we are thrilled that we can now offer Enhertu to even more patients."

The approval was granted under the FDA’s Real-Time Oncology Review programme after securing Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this setting. The expanded approval for Enhertu in the US, following its previous approval in 2nd-line HER2-positive metastatic breast cancer, enables its use across a wide spectrum of HER2-expressing breast cancer, including patients with HER2-low disease.

The DESTINY-Breast04 Phase III trial results were presented at the presidential plenary session of the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting and simultaneously published in The New England Journal of Medicine (NEJM).1

The safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) or pneumonitis rates were consistent with those observed in late-line HER2-positive breast cancer trials of Enhertu. Overall, 12% of patients had confirmed ILD or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events were Grade 1 or 2 (10%), with five Grade 3 (1.3%) and no Grade 4 events reported. There were three (0.8%) ILD-related deaths (Grade 5).

In June 2022, fam-trastuzumab deruxtecan-nxki (Enhertu) was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines) as the Category 1 preferred regimen for patients with tumours that are HER2 IHC 1+ or 2+ and ISH- who have received at least one prior line of chemotherapy for metastatic disease and, if tumour is HR-positive, are refractory to endocrine therapy, based on the data from DESTINY-Breast04.2

The US regulatory submission for DESTINY-Breast04 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Enhertu is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Switzerland’s Swissmedic.

Regulatory applications for Enhertu are also currently under review in Europe, Japan and several other countries based on the DESTINY-Breast04 results.

Notes

Financial considerations
Following this approval for Enhertu in the US, an amount of $200m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the HER2-low breast cancer post chemotherapy indication. The milestone will be capitalised as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised milestones, and will be amortised through the profit and loss statement.

Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as collaboration revenue in the Company’s financial statements.

Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.

Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide and in the US.3,4 More than two million patients with breast cancer were diagnosed in 2020 resulting in nearly 685,000 deaths globally.3 In the US, more than 290,000 patients are expected to be diagnosed in 2022, resulting in more than 43,000 deaths.5

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumours.6

HER2 expression is currently determined by an immunohistochemistry (IHC) test which estimates the amount of HER2 protein on a cancer cell, and/or an in-situ hybridisation (ISH) test, which counts the copies of the HER2 gene in cancer cells.6,7 HER2 tests provide IHC and ISH scores across the full HER2 spectrum and are routinely used to determine appropriate treatment options for patients with metastatic breast cancer.

HER2-positive cancers are currently defined as HER2 expression measured as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are defined as HER2 expression measured as IHC 0, IHC 1+ or IHC 2+/ISH-.6 However, approximately half of all breast cancers are HER2-low, defined as an HER2 score of IHC 1+ or IHC 2+/ISH-.8-10 HER2-low occurs in both HR-positive and HR-negative disease.11

Previously, patients with HR-positive metastatic breast cancer and HER2-low disease had limited effective treatment options following progression on endocrine (hormone) therapy.9,12 Additionally, few targeted options were available for those with HR-negative disease.13 Now with the approval of Enhertu, patients with HER2-low tumours may be eligible for HER2-directed therapy.

DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive or HR-negative, HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomised patients (HR-positive and HR-negative disease). Other secondary endpoints include PFS based on investigator assessment, objective response rate based on BICR and on investigator assessment, duration of response based on BICR and safety.

DESTINY-Breast04 enrolled 557 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu in breast, gastric and non-small cell lung cancer are currently under review in several other countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01, DESTINY-Gastric02 and DESTINY-Lung01 trials, respectively.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging and redefining the current clinical paradigm for how breast cancer is classified and treated to deliver even more treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the initial approvals of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On August 5, 2022 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a clinical-stage biopharmaceutical company developing innovative therapies designed to treat or reverse disease, reported financial results for the three and six months ended June 30, 2022 and provided a business update (Press release, Caladrius Biosciences, AUG 5, 2022, View Source [SID1234617687]).

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"The second quarter of 2022 was a transformative and energizing quarter for Caladrius with the announcement of our proposed merger with Cend Therapeutics ("Cend"). The merger process, which, when completed, will result in the change of our name to Lisata Therapeutics ("Lisata"), is progressing well and, subject to the approval by our stockholders, remains on track to close in the third quarter of 2022," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius. "Following the closing of the proposed merger, Lisata will focus on maximally exploiting the full potential of Cend’s CendR Platform technology in a range of solid tumor cancer settings while progressing Caladrius’ current product candidate development programs to their next development milestone. CEND-1, the lead product candidate from the CendR Platform, has the potential to be combined with a myriad of chemo and immunotherapeutic agents that could become an integral part of a revised standard-of-care therapy for many difficult to treat cancers."

"In June, Cend announced the first patient had been treated in the Phase 2b ASCEND study of CEND-1 in combination with gemcitabine and nab-paclitaxel for the treatment of first-line, metastatic pancreatic ductal adenocarcinoma ("mPDAC"). This 125-patient study is a double-blind, randomized, placebo-controlled clinical trial being conducted at up to 40 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Cancer Trials Group in collaboration with the NHMRC Clinical Trial Centre at the University of Sydney. In addition, The Lancet Gastroenterology and Hepatology recently published groundbreaking data from the Phase 1b study of CEND-1 in combination with gemcitabine and nab-paclitaxel for the treatment of first-line mPDAC."

Dr. Mazzo continued, "While we continue to make progress on our current Caladrius programs, a tremendous amount of work already has been conducted under our collaboration agreement with Cend. This is an exciting time for the Company and the future Lisata. We look forward to providing additional updates in the coming weeks and months."

Proposed Merger with Cend Therapeutics

As previously disclosed, the Company entered into a definitive merger agreement with Cend Therapeutics, Inc., a privately held, clinical-stage biotechnology company focused on a novel approach to enable more effective treatments for solid tumor cancers, under which Cend will merge with a wholly owned subsidiary of Caladrius in an all-stock approximate "merger of equals" transaction unanimously approved by the Boards of Directors of each company. Following closing, the combined company is expected to be renamed Lisata Therapeutics, Inc. and is expected to trade on the Nasdaq Capital Market under the ticker symbol "LSTA". The merger is currently expected to close in the third quarter of 2022 subject to the approval of Caladrius and Cend stockholders as well as the satisfaction of certain other customary closing conditions and applicable approvals. In the interim, Caladrius has made an investment of $10 million in Cend in connection with a collaboration agreement to maintain development momentum of the Cend pipeline.

Ongoing Development Portfolio Update

HONEDRA (CLBS12) for the treatment of critical limb ischemia ("CLI")

HONEDRA is the Company’s SAKIGAKE-designated product candidate for the treatment of CLI and Buerger’s disease in Japan which is now in the pre-consultation phase of the registration process with the Pharmaceuticals and Medical Devices Agency ("PMDA") in Japan. Data from the follow-up of all patients completed in the registration-eligible clinical trial in Japan has been compiled and will be reviewed by PMDA during the third quarter of 2022, after which the PMDA will provide important perspective to be considered in preparation for the formal consultation meetings which precede the Japanese new drug application. Concomitantly, the Company will focus its efforts to secure a Japanese partner to complete the remaining steps to produce registration in Japan.

XOWNA (CLBS16) for the treatment of coronary microvascular dysfunction ("CMD")

XOWNA is an experimental regenerative therapy for the treatment of CMD. It was the subject of a positive Phase 2a study (the "ESCaPE-CMD trial") reported in 2020 and is currently being evaluated in a U.S. Phase 2b study (the "FREEDOM Trial"). The FREEDOM Trial was originally designed as a 105-patient double-blind, randomized, placebo-controlled trial to further evaluate the efficacy and safety of intracoronary delivery of autologous CD34+ cells (XOWNA) in subjects with CMD and without obstructive coronary artery disease and was expected to complete enrollment in approximately 12 months. As previously communicated, enrollment in the FREEDOM Trial initially proceeded as planned with the first patient treated in January 2021; however, the impact of the COVID-19 pandemic in the U.S., coupled with supply chain issues associated with the catheters used for diagnosis of CMD and/or administration of XOWNA, as well as with a contrast agent typically used in many catheter laboratories, have made and continue to make enrollment much slower than originally predicted and challenging to accelerate. As a result, and as previously disclosed, the Company has suspended further enrollment activities and is conducting an interim analysis of the data during the third quarter of 2022 to determine the next steps for the program, which may require a discussion with and guidance from FDA. The Company expects to have a decision on next steps for the program by the end of 2022.

CLBS201 for the treatment of diabetic kidney disease ("DKD")

Progressive kidney failure is associated with attrition of the microcirculation of the kidney. Preclinical studies in kidney disease and injury models have demonstrated that protection or replenishment of the microcirculation results in improved kidney function. Based on these observations, the Company recently initiated a Phase 1b, open-label, proof-of-concept trial evaluating CLBS201, a CD34+ regenerative cell therapy investigational product for intra-renal artery administration in patients with DKD. Patients selected for the study are in the pre-dialysis stage of kidney disease and exhibit rapidly progressing stage 3b disease. The protocol provides for a cohort of six patients overseen by an independent Data Safety Monitoring Board with the objective of determining the tolerance of intra-renal cell therapy injection in DKD patients as well as the ability of CLBS201 to regenerate kidney function. A key read-out of data will occur at the 6-month follow-up visit for all patients. The Company treated the first patient in April 2022 and completed treatment for all six subjects during the third quarter of 2022. Top-line data is anticipated from all subjects by the first quarter of 2023.

Second Quarter 2022 Financial Highlights

Research and development expenses for the three months ended June 30, 2022 were $3.2 million, compared to $4.3 million for the three months ended June 30, 2021, representing a decrease of $1.1 million or 25%. This decrease was primarily due to a decrease in expenses associated with HONEDRA in Japan, revenue received from the collaboration agreement and one-off recruiting expenses in the prior year. Research and development activities in the current year period focused on the advancement of our ischemic repair platform and related to:

execution of the FREEDOM Trial including preparation for an interim analysis;
execution of the Phase 1b proof-of-concept trial of CLBS201 as a treatment for DKD, which commenced in the first quarter of 2022 with the first patient in the study treated in April 2022; and
study close out activities and preparation for the pre-consultation meetings with the PMDA for HONEDRA in CLI and Buerger’s disease in Japan.
General and administrative expenses, which focus on general corporate related activities, were $3.5 million for the three months ended June 30, 2022, compared to $2.8 million for the three months ended June 30, 2021, representing an increase of 24%. This increase was primarily due to an increase in professional fees associated with the proposed merger with Cend Therapeutics, Inc.

Overall, net losses were $6.6 million and $5.7 million for the three months ended June 30, 2022 and June 30, 2021, respectively.

In order to provide Cend with capital for its development programs prior to the closing of the merger, the Company made an investment of $10 million in Cend in connection with a collaboration agreement to maintain development momentum of the Cend pipeline.

Balance Sheet Highlights

As of June 30, 2022, the Company had cash, cash equivalents and marketable securities of approximately $73 million, which is net of our $10 million investment in Cend and which we believe positions us well relative to the projected capital obligations for our existing development programs as well as our cash and investments balance target at the time of the closing of the merger with Cend.

Conference Call Information

Caladrius will hold a live conference call today, August 4, 2022, at 4:30 p.m. (EDT) to discuss financial results, provide a business update and answer questions.

The Company is utilizing a new conference call service. Those wishing to participate must register for the conference call by way of the following link: CLICK HERE TO REGISTER. Registered participants will receive an email containing conference call details for dial-in options. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time.

A live webcast of the call will also be accessible under the Investors & News section of the Caladrius website and will be available for replay beginning two hours after the conclusion of the call for 12 months.

On August 5, 2022 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a late clinical stage biopharmaceutical company focused on helping patients fight cancer with oncolytic viral immunotherapies, reported financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, Candel Therapeutics, AUG 5, 2022, View Source [SID1234617688]).

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"Candel remains on track to achieve several milestones in the second half of 2022," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "We are encouraged by the initial phase 2 clinical trial data for CAN-2409 in non-small cell lung cancer presented in June at ASCO (Free ASCO Whitepaper). The data presented at ASCO (Free ASCO Whitepaper) showed an 87.5 percent disease control rate in heavily pretreated patients whose cancer was progressing on PD-1 agents at clinical trial entry. In the second half of this year, we are planning for multiple inflection points, including updated clinical data from the phase 2 lung cancer clinical trial, initiation of a phase 3 clinical trial in high-grade glioma, and we will present initial data from our enLIGHTEN Discovery Platform. I am thrilled to see the rapid progress the Candel team continues to make on the discovery and development of our oncolytic viral immunotherapies for patients with cancer."

Second Quarter 2022 & Recent Highlights

Presented initial data on its open-label phase 2 clinical trial of CAN-2409 in combination with anti-PD-1 or PD-L1 targeting agents in patients with stage III/IV non-small cell lung cancer (NSCLC) in June 2022.
The data showed cytotoxic T cell response and a disease control rate of 87.5 percent achieved in patients whose cancer was progressing on anti-PD-1 therapy at clinical trial entry.
These findings were presented by co-principal investigator Charu Aggarwal, MD, MPH, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
In addition to the ASCO (Free ASCO Whitepaper) poster session, the Company hosted a discussion with key experts Roy Herbst, MD, PhD, and Daniel Sterman, MD, to review these initial data.
The Company appointed three new members to its Board of Directors: Gary Nabel, MD, PhD, renowned virologist and immunologist; Joseph Papa, prominent business leader; and Renee Gaeta, strategic financial expert. Effective August 8, 2022, these new members will replace current Board members: Alan E. Smith, PhD, Shaan Ghandi, MD, D.Phil, and Udi Meirav, PhD, maintaining Candel’s nine-seat Board.
Key Upcoming Milestones

In the fourth quarter of 2022, the Company expects to present new data from three clinical trials:
A phase 1b clinical trial of CAN-2409 in combination with nivolumab (Opdivo) combined with standard of care in first line treatment in patients with high-grade glioma.
A phase 1 clinical trial of CAN-3110 in patients with recurrent high-grade glioma.
A phase 2 clinical trial of CAN-2409 in combination with anti-PD-1 or PD-L1 agents in patients with stage III/IV NSCLC.
The Company anticipates initiating a phase 3 clinical trial evaluating CAN-2409 in patients with high-grade glioma in the third quarter of 2022.
The Company also plans to debut initial data from its new discovery platform, enLIGHTEN, in the fourth quarter of 2022.
Financial Results for the Quarter Ended June 30, 2022

Cash Position: Cash and cash equivalents as of June 30, 2022 were $86.8 million compared to $82.6 million as of December 31, 2021. The net increase was due to receipt of $20.0 million from a term loan with Silicon Valley Bank in February 2022, offset by costs to fund operating activities and the purchase of fixed assets. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will be sufficient to fund its operations into the first quarter of 2024.

Research and Development Expenses: Research and development expenses were $5.0 million and $10.4 million for the three- and six-month period ended June 30, 2022 compared to $3.3 million and $6.0 million for the comparable periods in 2021. The increase was primarily due to personnel-related costs for additional headcount, as well as operating expenses related to the conduct of five ongoing clinical studies, the expected initiation of a phase 3 clinical study, and the expansion of manufacturing capabilities. Excluding stock-based compensation expense of $57,000 for the three months ended June 30, 2022 and $199,000 for the six-month period ended June 30, 2022, research and development expenses for the three- and six-month period ended June 30, 2022 were $5.0 million and $10.2 million.

General and Administrative Expenses: General and administrative expenses were $3.8 million and $7.4 million for the three- and six-month period ended June 30, 2022 compared to $2.0 million and $4.0 million for the comparable periods in 2021. The increase was primarily due to higher insurance costs, personnel-related costs and professional consulting fees associated with operating as a public company. Excluding stock-based compensation expense of $381,000 for the three-month period ended June 30, 2022, and $730,000 for the six-month period ended June 30, 2022, general and administrative expenses for the three- and six-month period ended June 30, 2022 were $3.4 million and $6.6 million.

Total Operating Expenses: Total operating expenses were $8.8 million and $17.8 million for the three- and six-month period ended June 30, 2022 compared to $5.3 million and $10.0 million for the comparable periods in 2021. The increase was primarily due to increased personnel-related costs and research and development activities and resulting expenses as well as increased operating expenses associated with being a public company. Excluding stock-based compensation expense of $438,000 for the three-month period ended June 30, 2022, and $929,000 for the six-month period ended June 30, 2022, total operating expenses for the three- and six-month period ended June 30, 2022 were $8.3 million and $16.9 million.

Net Loss: Net loss was $4.1 million and $5.0 million for the three- and six-month period ended June 30, 2022, as compared to $17.1 million and $21.6 million for the comparable periods in 2021. The net loss for the three- and six-month period ended June 30, 2022 includes a non-cash credit of $5.0 million and $13.3 million, and the net loss for the three- and six-month period ended June 30, 2021 includes a non-cash charge of $12.4 million for the change in the fair value of the Company’s warrant liability, and includes stock-based compensation expense of $438,000 and $929,000 for the three- and six-month period ended June 30, 2022, and $1.1 million and $1.5 million for the three- and six-month period ended June 30, 2021. Excluding non-cash credits for the changes in the warrant liability and charges for stock-based compensation, the net loss for the three- and six-month period ended June 30, 2022 was $8.7 million and $17.4 million, as compared to $3.6 million and $7.7 million for the comparable periods in 2021.

On August 5, 2022 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported financial results for the second quarter ended June 30, 2022 (Press release, Cellectar Biosciences, AUG 5, 2022, View Source [SID1234617689]).

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"During the second quarter, iopofosine passed an important milestone as an independent data monitoring committee completed a futility/efficacy assessment and unanimously recommended continuation of our pivotal Phase 2B trial in Waldenstrom’s macroglobulinemia (WM)," said James Caruso, president and CEO of Cellectar. "This global trial includes participation from leading institutions and world-renowned WM thought leadership, and we are excited by the active engagement of our investigators." Mr. Caruso continued, "We also look forward to providing data from our phase 2a multiple myeloma trial and our phase 1 pediatric trial for malignant brain tumors and sarcomas in the second half of 2022."

Second Quarter 2022 Financial Highlights

Cash and Cash Equivalents: As of June 30, 2022, the company had cash and cash equivalents of $24.8 million, compared to $35.7 million as of December 31, 2021. Net cash used in operating activities during the six months ended June 30, 2022 was approximately $10.8 million. The company believes its cash on hand is adequate to fund basic budgeted operations into the third quarter of 2023.

Research and Development Expense: R&D expense for the three months ended June 30, 2022 was approximately $4.5 million, which was relatively consistent when compared to approximately $4.6 million for the three months ended June 30, 2021. For the six months ended June 30, 2022, R&D expense was approximately $8.4 million, while the comparable period in 2021 was $9.3 million. The reduction in the six month period was due primarily to the timing of activities related to our ongoing WM pivotal trial as trial initiation costs were higher in the prior year.

General and Administrative Expense: G&A expense for the three months ended June 30, 2022 was $2.9 million, compared to $1.4 million for the same period in 2021. G&A expense in the six months ended June 30, 2022 was approximately $5.2 million, as compared to approximately $3.1 million in the prior year. These increases were driven largely by increased professional fees and personnel costs.

Net Loss: The net loss attributable to common stockholders for the quarter ended June 30, 2022 was ($7.4) million, or ($1.22) per share, compared to ($6.0) million, or ($1.14) per share, in the quarter ended June 30, 2021, while the loss attributable to common stockholders in the first half of 2022 was ($13.6) million, or ($2.22) per share, compared to ($12.4) million, or ($2.45) per share for the first half of 2021.

On August 5, 2022 Celyad Oncology SA (Euronext & Nasdaq: CYAD) (the "Company"), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported an update on its financial results and recent business developments for the first half ended June 30, 2022 (Press release, Celyad, AUG 5, 2022, View Source [SID1234617690]).

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"As the Company continues to evolve, we are excited about a renewed focus on additional value drivers for Celyad Oncology. Importantly, with our world-class intellectual property focused on allogeneic CAR T technology, we have multiple opportunities for partnerships with peers in the industry," commented Michel Lussier, interim Chief Executive Officer of Celyad Oncology. "We also were proud to recently announce that the FDA lifted the clinical hold on our CYAD-101 program. In addition, we look forward to the upcoming data read out for CYAD-211 in the second half of 2022. We are truly ushering in a new chapter for Celyad Oncology by unlocking the potential of not only our product candidates, but also our portfolio of IP, technology, and overall expertise in cell therapy."

Second Quarter 2022 and Recent Business Highlights

The Board of Directors named Hilde Windels as Chair of the Board of Directors
Michel Lussier named Interim Chief Executive Officer of the Company
Pipeline and Business Updates

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM

CYAD-211 is an investigational, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of r/r MM. CYAD-211 is engineered to co-express a B cell maturation antigen (BCMA) targeting CAR and a single shRNA, which interferes with the expression of the CD3ζ component of the T-cell receptor (TCR) complex.

Preliminary data reported in December 2021 from the dose-escalation segment of the IMMUNICY-1 Phase 1 trial evaluating CYAD-211 following cyclophosphamide/fludarabine (CyFlu) preconditioning chemotherapy in patients with r/r MM showed evidence of clinical activity with a good tolerability profile including no evidence of Graft versus Host Disease. In addition, all patients in the trial had detectable CYAD-211 cells in the peripheral blood.
Enrollment is currently ongoing in the IMMUNICY-1 Phase 1 trial to evaluate enhanced lymphodepletion (eLD) and increased CYAD-211 doses with the aim to improve cell persistence and potentially maximize the clinical benefit of CYAD-211. The IMMUNICY-1 protocol also allows for CYAD-211 redosing in certain patients.
Additional data updates from the eLD cohorts of the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half of 2022.
CYAD-101 – Allogeneic TIM-based NKG2D CAR T for mCRC

CYAD-101 is an investigational, non-gene edited, allogeneic CAR T candidate engineered to co-expresses the TIM peptide alongside a CAR based on NKG2D, a receptor expressed on natural killer (NK) and T cells, that binds to eight stress-induced ligands.

In June 2022 we submitted our complete response to the clinical hold of the CYAD-101-002 phase 1b trial to the FDA stating our intent to amend the eligibility criteria to exclude patients who have bilateral lung metastases and patients who have received treatment with epidermal growth factor receptor (EGFR) targeting monoclonal antibodies within the previous 9 months prior to trial recruitment. In July 2022, based on that complete response, we received notification that the FDA lifted the clinical hold on the CYAD-101-002 phase 1b trial
shARC Platform

Discovery research continues on programs focused on the co-expression of Interleukin-18 in conjunction with our short hairpin RNA shRNA technology platform, also known as our shARC (shRNA Armored CAR) franchise, with a focus on the development of next-generation, allogeneic CAR T candidates.

CYAD-02 – Autologous NKG2D CAR-T for r/r AML and MDS

CYAD-02 is an investigational, autologous CAR T therapy that co-expresses both the NKG2D CAR and a single shRNA targeting the NKG2D ligands MICA/MICB on the CAR T cells.

In December 2021, the Company presented clinical results from the dose-escalation CYCLE-1 Phase 1 trial evaluating CYAD-02 for the treatment of r/r acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data from the trial showed that a single shRNA can target two independent genes (MICA/MICB) to enhance the phenotype of the CAR T cells. In addition, the dual knockdown showed a positive contribution to the initial clinical activity of CYAD-02 as well as a trend towards increased engraftment and persistence compared to the first-generation, autologous NKG2D receptor CAR T.
The Company continues to explore potential partnership opportunities for the future development of CYAD-02.
Strategic Focus on Intellectual Property

The Company maintains a robust intellectual property portfolio within the landscape of CAR T, including twelve foundational U.S.

patents associated with allogeneic CAR T for the treatment of cancer as well as patents for NKG2D receptor-based cell therapies. We believe these patents provide an avenue for the Company to develop its own programs as well as to seek potential partnership opportunities.

First Half 2022 Financial Results

Key financial figures for the first half of 2022, compared with the first half of 2021 and full year 2021, are summarized below:

Research and Development expenses were €10.5 million for the first half of 2022, compared to €10.0 million for the first half of 2021. The €0.5 million increase was mainly driven by intellectual property filing and maintenance fees to strengthen intellectual property prosecution and the increase of employee expenses mainly related to the full expense impact of the employees recruited during 2021 to support the Group’s preclinical and clinical programs, employee turnover and management changes, both of which were partially offset by the decrease in clinical activities resulting from the Phase 1b CYAD-101-002 (KEYNOTE-B79) trial which was on clinical hold during the second quarter of 2022.

General and Administrative expenses were €6.2 million for the first half of 2022, compared to €4.8 million for the first half of 2021. This increase is primarily attributable to an increase in insurance costs for the period, combined with an increase in employee expenses mainly related to management changes through the six-month period ended June 30, 2022.

A fair value adjustment of €1.1 million (non-cash income) related to the reassessment of the contingent consideration and other financial liabilities associated with the advancement of the Company’s NKG2D-based CAR T candidates as of June 30, 2022, required by International Financial Reporting Standards (IFRS), was mainly driven by the updated assumptions on projected revenue associated with the Company’s CYAD-101 program, for which the timing of the potential commercialization has been delayed by one year. Additionally, the addressable patient population for CYAD-101 has been reduced based on recent safety findings from the CYAD-101-002 Phase 1b trial. The fair value adjustment was also driven by updated assumptions to discount rate and revaluation of the U.S. dollar foreign exchange rate.

The Company also posted €1.6 million in net other income for the first half of 2022, compared to a net other income of €1.8 million for the first half of 2021. Other income for the first half of 2022 is primarily due to grant income from the Walloon Region of €1.4 million.

Net loss for the first half of 2022 was €14.1 million, or € (0.62) per share, compared to a net loss of €14.9 million, or € (1.02) per share, for the first half of 2021.

Net cash used in operations was €16.3 million for the first half of 2022, compared to €12.2 million for the first half of 2021.

As of June 30, 2022, the Company had cash and cash equivalents of €14.4 million ($15.0 million).

As of June 30, 2022, the total number of basic shares outstanding were 22.6 million similar to December 31, 2021.

Celyad Oncology First Half 2022 Conference Call Details

The conference call will be webcast live and archived within the "Events" section of the Celyad Oncology website.