On July 13, 2021 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that dosing of the first patient in the Company’s multi-cohort Phase 1/2 study of oral fadraciclib in patients with advanced solid tumors (Press release, Cyclacel, JUL 13, 2021, View Source [SID1234584817]).

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"Advancing oral fadraciclib, our lead candidate, into this Phase 1/2 trial, represents a key clinical milestone and corporate objective for our team," said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "This is the first of four streamlined Phase 1/2 studies we plan to open over the coming months as we expand our clinical programs to evaluate the potential of fadraciclib and CYC140, our oral PLK1 inhibitor, first in solid tumors and lymphomas and then in leukemias. We look forward to providing periodic updates on our clinical progress and data from these open-label studies."

"We are pleased to have dosed the first patient in this study and are delighted by the enthusiasm and strong interest from current and prospective investigators," said Mark Kirschbaum M.D., Senior Vice President & Chief Medical Officer of Cyclacel. "The study has initially opened at City of Hope and MD Anderson Cancer Center with more sites to join later on. We are building an excellent network of participating institutions both in terms of clinical and scientific expertise. In previous studies with single agent, intravenous fadraciclib we have observed durable suppression of MCL1 and other mechanistically-related proteins, including cyclin E and MYC, at tolerated doses. In addition, a patient with MCL1 amplified, advanced endometrial cancer experienced deep PR and 100% shrinkage of her target tumor lesions on single agent fadraciclib treatment. We are excited to begin mid-stage development of fadraciclib with the objective of registration-enabling outcomes and offering a new treatment option for patients with advanced solid tumors or lymphomas."

"Based upon prior clinical activity shown to date, further exploration of this novel CDK2/9 inhibitor is warranted across a number of solid tumor histologies," said Miguel Villalona-Calero, M.D., co-leader of the Developmental Cancer Therapeutics Program and Professor, Department of Medical Oncology & Therapeutics Research at the City of Hope, a world-renowned, independent research and treatment center for cancer, diabetes and other life-threatening diseases. "We look forward to enrolling patients in this trial and evaluating the potential treatment benefit of this experimental therapy both as a single agent and in combinations."

The Phase 1/2 registration-directed trial (CYC065-101) uses a streamlined design and will first determine the recommended Phase 2 dose (RP2D) for single-agent, oral fadraciclib. Once RP2D has been established, the trial will immediately enter into proof-of-concept, cohort stage, using a Simon 2-stage design, where single agent fadraciclib will be administered to patients in up to eight cohorts defined by histology thought to be sensitive to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies. The cohorts will include patients with breast cancer (selected for metastatic, hormone receptor positive, HER-2 negative, post-CDK4/6 inhibitor; HER-2 refractory; or triple negative), colorectal (including KRAS mutant), endometrial, hepatocellular and ovarian cancers, as well as certain lymphomas. An additional basket cohort will enroll patients with biomarkers relevant to the drug’s mechanism, including MCL1, MYC and cyclin E, regardless of histology. The protocol allows for expansion of a cohort based on response which may allow acceleration of the clinical development and registration plan for fadraciclib.

About Cyclin-Dependent Kinases and Fadraciclib

Cyclin-dependent kinases (CDKs) are critical for cell cycle control and transcriptional regulation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased cancer cell survival. Fadraciclib, a next generation CDK inhibitor, is a highly selective, potent, orally and intravenously available, inhibitor of CDK2 and CDK9. CDK2 drives cell cycle transitions and CDK9 regulates transcription of genes through phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II). By inhibiting CDK2 and CDK9 fadraciclib causes apoptotic death of cancer cells at sub-micromolar concentrations.

Preclinical data suggest that fadraciclib may benefit patients with certain cyclin E-addicted or MYC-amplified solid tumors, including certain forms of breast cancer, neuroblastoma, ovarian cancer, uterine serous carcinoma and adult and pediatric hematological malignancies, such as ALL, AML, B-cell lymphoma, CLL, and multiple myeloma. Similarly to FDA-approved CDK4/6 inhibitors, fadraciclib may be useful in combination with other anticancer drugs, including HER2 inhibitors, such as trastuzumab, or BCL2 inhibitors, such as venetoclax.

In a prior Phase 1 open-label trial (CYC065-01), patients with high copy CCNE (cyclin E), MYC or MCL1 showed sensitivity to intravenously-administered, single-agent fadraciclib. A heavily pretreated patient with MCL1 amplified endometrial cancer achieved a radiographically confirmed partial response (PR) after a month and a half on fadraciclib. This patient continues on therapy for almost two years and reduction in her target tumor lesions has reached 100%. An additional patient with cyclin E amplified ovarian cancer achieved stable disease with 29% shrinkage in her target tumor lesions.

On July 13, 2021 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported preliminary unaudited net revenue of $135.6 million for the second quarter of 2021 (Press release, Pacira Pharmaceuticals, JUL 13, 2021, View Source [SID1234584814]). The company’s total revenues include net product sales of EXPAREL (bupivacaine liposome injectable suspension) and iovera°, which were $130.1 million and $3.8 million for the second quarter of 2021 and $45.8 million and $1.4 million, respectively, for the month of June 2021. EXPAREL average daily sales were 178% and 120% of the prior year levels for the second quarter and month of June 2021, respectively. The company reports average daily growth rates for EXPAREL to normalize for differences in the number of selling days per reporting period. The number of EXPAREL selling days were 22, 20, and 22 for the months of April, May, and June, respectively, in both 2021 and 2020.

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"We are encouraged by the continued robust growth in EXPAREL sales with the second quarter of 2021 coming in at record levels despite the barrier of COVID-19 for many elective surgery procedures. As conditions normalize in the second half of 2021, we anticipate increasing opportunity for EXPAREL expansion," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "The surgical market is accelerating its transition to outpatient settings, facilitated by our wealth of clinical data and experience to support EXPAREL-based regional approaches across a growing number of complex surgical settings. Additionally, interest in iovera° continues to mount with our educational and commercial programs highlighting its ability to deliver drug-free pain control that endures for several months. Throughout the balance of the year, we will continue to build on our established momentum as the industry leader of non-opioid pain management and regenerative health solutions."

The company’s 2021 product sales continue to be negatively impacted by the COVID-19 pandemic, which mandated significant postponement or suspension in the scheduling of elective surgical procedures resulting from public health guidance and government directives. EXPAREL sales in the second quarter of 2020 were significantly disrupted when the COVID-19 pandemic was at its peak and elective surgeries were largely prohibited. Elective surgery restrictions began to lift on a state-by-state basis in April 2020 and EXPAREL average daily sales returned to year-over-year growth in June 2020.

In order to provide greater transparency, the company will continue to report monthly intra-quarter unaudited net product sales until it has gained enough visibility around the impacts of COVID-19. The company is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com. The financial information included in this press release is preliminary, unaudited, and subject to adjustment. It does not present all information necessary for an understanding of the company’s financial results for the second quarter or full year 2021.

On July 13, 2021 Nurix Therapeutics Inc. (Nasdaq: NRIX), a biopharmaceutical company developing targeted protein modulation drugs, reported financial results for the second quarter ended May 31, 2021 and provided a corporate update (Press release, Nurix Therapeutics, JUL 13, 2021, View Source [SID1234584813]).

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"Our first clinical trial to evaluate NX-2127, an orally bioavailable degrader of Bruton’s tyrosine kinase with immunomodulatory drug activity in patients with relapsed or refractory B-cell malignancies is actively recruiting, and we anticipate sharing preliminary data from the dose escalation by year-end 2021," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "The second half of 2021 promises to be an exciting time for Nurix as we prepare to deliver on our ambitious goal of initiating Phase 1 trials for three additional wholly owned and internally developed drug candidates."

Recent Business Highlights

Expanded the Leadership Team with the Addition of a Chief Operating Officer: Nurix announced the appointment of Stefani A. Wolff as chief operating officer and executive vice president of product development. Ms. Wolff brings to Nurix over 30 years of leadership experience in oncology and immunology most recently from Principia Biopharma Inc., where she served as chief development officer and formerly senior vice president of strategy and operations overseeing Principia’s portfolio including Bruton’s tyrosine kinase (BTK) targeted agents.
Strengthened the Board of Directors with a Highly Successful Biotechnology Executive: Nurix announced the appointment of Clay Siegall, Ph.D., president, chief executive officer and chairman of Seagen (formerly Seattle Genetics, Inc.), to its board of directors. Dr. Siegall is an industry leader with a remarkable track record of success in building Seagen from a drug discovery platform company to a commercial-stage oncology company with multiple products. Dr. Siegall co-founded Seagen in 1998, which today has three FDA-approved medicines and is an industry leader in antibody-drug conjugate technology and development.
Presented Preclinical Data Highlighting Activity of NX-5948 in Animal Models of Autoimmune Disease: Nurix presented preclinical data for NX-5948 at the European Alliance of Associations for Rheumatology (EULAR) 2021 Virtual Congress in June 2021. The data presented at the EULAR Congress demonstrate that NX-5948 is a highly selective and potent degrader of BTK in primary human B cells resulting in robust inhibition of B cell activation. Importantly, data obtained from a mouse model of collagen-induced arthritis (CIA) demonstrated that in mice treated with NX-5948, symptoms of arthritis improved, with a significant reduction in arthritis clinical score, superior disease-related symptom control relative to ibrutinib, and similar activity to that of dexamethasone. A copy of the poster can be found on Nurix’s website.
Upcoming Program Highlights

NX-2127: Nurix’s lead drug candidate from its protein degradation portfolio, NX-2127, is an orally bioavailable degrader of BTK with immunomodulatory drug (IMiD) activity for the treatment of relapsed or refractory B-cell malignancies. Nurix is actively recruiting patients at multiple clinical sites for a Phase 1 clinical trial of NX-2127. Initial pharmacokinetic (PK) and pharmacodynamic (PD) data from the dose escalation portion of the trial is anticipated by year-end 2021 (expected timing of events here and throughout the press release are based on calendar year quarters). Additional information on the clinical trial can be accessed at ClinicalTrials.gov (NCT04830137).
NX-1607: Nurix’s lead drug candidate from its E3 ligase inhibitor portfolio, NX-1607, is an orally bioavailable inhibitor of CBL-B for immuno-oncology indications. Nurix anticipates initiating a Phase 1 trial for NX-1607 in the second half of 2021.
NX-5948: Nurix’s second drug candidate from its protein degradation portfolio, NX-5948, is an orally bioavailable BTK degrader designed without IMiD activity for certain B-cell malignancies and autoimmune diseases. Nurix anticipates initiating a Phase 1 trial for NX-5948 in patients with hematologic malignancies in the second half of 2021 and is planning for the potential expansion of indications into selected autoimmune diseases in 2022.
DeTIL-0255: Nurix’s lead candidate in its cellular therapy portfolio, DeTIL-0255, is a drug-enhanced adoptive cellular therapy. Nurix anticipates initiating a Phase 1 trial for DeTIL-0255 in the second half of 2021.
Fiscal Second Quarter 2021 Financial Highlights

Collaboration revenue for the three months ended May 31, 2021 was $7.1 million compared to $4.2 million for the three months ended May 31, 2020. The increase was due to the continued scale up of internal resources and external spending for our collaborations with Sanofi and Gilead as compared to the prior period, resulting in a higher percentage of completion and therefore more revenue recognized in the current period.

Research and development expenses for the three months ended May 31, 2021 were $26.0 million compared to $14.1 million for the three months ended May 31, 2020. The increase was primarily related to an increase of $5.3 million in compensation and related personnel costs attributable to an increase in headcount and higher non-cash stock-based compensation expense. There was also an increase of $4.7 million attributable to increases in preclinical development activities and drug discovery research and an increase of $1.1 million in clinical costs due to the start of clinical trial patient enrollment.

General and administrative expenses for the three months ended May 31, 2021 were $7.5 million compared to $3.3 million for the three months ended May 31, 2020. The increase was primarily related to an increase of $3.0 million in compensation related expenses attributable to a higher headcount and higher non-cash stock-based compensation expense. There was also an increase of $1.1 million in consultant and other professional service expenses primarily related to becoming a public company.

Net loss for the three months ended May 31, 2021 was $26.4 million, or ($0.60) per share, compared to net income of $7.6 million for the three months ended May 31, 2020, or $0.00 per share attributable to common shareholders under accounting rules associated with Nurix preferred shares prior to their conversion to common shares on July 28, 2020.

Cash, Cash Equivalents and Investments: As of May 31, 2021, Nurix had cash, cash equivalents and investments of $496.5 million compared to $372.0 million as of November 30, 2020. The increase was primarily attributable to the net proceeds of $150.1 million from Nurix’s follow-on offering in March 2021.

On July 8, 2021 (the "Amendment Effective Date"), Navidea Biopharmaceuticals, Inc. (the "Company") reported that it entered into an Amendment to Stock Purchase Agreement and Letter of Investment Intent (the "Amendment") with Keystone Capital Partners, LLC ("Investor") pursuant to which Investor agreed to purchase 22,077 shares of Series D Redeemable Convertible Preferred Stock ("Series D Preferred Stock") on or before July 9, 2021 at 5 p.m. Eastern Time for an aggregate purchase price of $2,207,700 (Filing, 8-K, Navidea Biopharmaceuticals, JUL 13, 2021, View Source [SID1234584812]). The Amendment amends that certain Stock Purchase Agreement and Letter of Investment Intent (the "Purchase Agreement") dated August 31, 2020 between the parties, pursuant to which Investor agreed to purchase 150,000 shares of Series D Preferred Stock for an aggregate purchase price of $15,000,000 before the end of the nine-month period following the date when the Company’s registration statement on Form S-1 filed pursuant to the Purchase Agreement was declared effective. Prior to the Amendment Effective Date, Investor had purchased 72,500 shares of Series D Preferred Stock pursuant to the Purchase Agreement, leaving a remaining balance of 77,500 shares of Series D Preferred Stock. After purchasing 22,077 of the remaining shares, Investor has no further right or obligation to purchase shares of Series D Preferred Stock pursuant to the Purchase Agreement. The Amendment also contains a customary mutual release provision.

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On July 13, 2021 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that it has received approval from the Bioethics Committee of the Medical University of Karol Marcinkiewicz in Poznań (Ethics Committee) as well as an allowance from the Polish Department of Registration of Medicinal Products (URPL) for a protocol amendment for its Phase 1/2 evaluating Annamycin for the treatment of subjects with acute myeloid leukemia (AML) that is refractory to or relapsed after induction therapy (Press release, Moleculin, JUL 13, 2021, View Source [SID1234584811]).

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Annamycin is the Company’s next-generation anthracycline that has demonstrated a lack of cardiotoxicity in recently conducted human clinical trials for the treatment of AML. Additionally, Annamycin has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. The Company believes that the use of Annamycin may not face the same usage limitations imposed on doxorubicin. Annamycin is currently in development for the treatment of AML and STS lung metastases.

"Based on the preliminary data seen demonstrating clinical benefit for patients receiving a full course of treatment in the 240 mg/m2 cohort and the recommendation from our medical advisors on the dose limiting toxicity criteria, we are pleased to have Ethics Committee approval and the allowance from the URPL to amend the protocol for future patients. This amendment will allow us to continue dose escalation in the Phase 1 portion of the trial and establish the maximum tolerated dose as we work toward the recommended dose for the Phase 2 portion of the study. Our team is committed to advancing this important clinical program forward and to potentially address the limitations with current treatment options for AML patients," commented Walter Klemp, Chairman and CEO of Moleculin.

The Phase 1/2 AML trial in Poland remains ongoing and is currently dosing patients at 240 mg/m2. Under the previous protocol transient elevated liver enzymes (AST and ALT) observed in two patients were considered a dose limiting toxicity (DLT), which investigators believe would inappropriately limit the potential for continued dose escalation. The amendment to the Annamycin clinical trial protocol allows for a change in the DLT criteria as it relates to transient grade 3 elevations and allows dosing of three additional patients in the 240 mg/m2 cohort. If no DLT (as defined by the new criteria) is experienced with these next three patients, the Company plans to escalate dosing in new cohorts by 30 mg/m2 instead of the 60 mg/m2 previously planned, and with a de-escalation of 15 mg/m2 at the DLT dose if future patients experience a DLT.

The results from the Phase 1 portion of the Company’s U.S. Phase 1/2 clinical trial of Annamycin for the treatment of AML met its primary endpoint and demonstrated a clean safety profile with no evidence of cardiotoxicity when delivered to patients at or below the lifetime maximum anthracycline dose established by the FDA. To date, an independent expert assessment of the absence of cardiotoxicity in the first 19 patients treated with Annamycin in both the Company’s U.S. and European Phase 1 clinical trials in which an independent expert concluded that he "does not see evidence of cardiotoxicity."

Moleculin Biotech expects to continue reporting cohort topline results from the ongoing Phase 1/2 study for treatment of AML and to report the study’s topline results in the second half of 2022. Annamycin has been granted Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML.