On August 15, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapies for patients with hematologic and solid cancers and other serious diseases, reported financial results for the quarter ended June 30, 2022 (Press release, Gamida Cell, AUG 15, 2022, View Source [SID1234618381]). Net loss for the second quarter of 2022 was $18.6 million, compared to a net loss of $23.6 million in the second quarter of 2021. As of June 30, 2022, Gamida Cell had total cash, cash equivalents and investments of $55.1 million.

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Recently, Gamida Cell:

Received acceptance for filing from the U.S. Food and Drug Administration (FDA) with priority review for its Biologics License Application (BLA) for omidubicel. The BLA has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2023. If approved, omidubicel will be the first allogeneic advanced stem cell therapy donor source for patients with blood cancers in need of a stem cell transplant.
Dosed the first patient in a company-sponsored Phase 1/2 study evaluating a cryopreserved formulation of GDA-201, a readily available cell therapy candidate for the treatment of follicular and diffuse large B-cell lymphomas.
Continued development of the company’s proprietary NAM-enabled NK cell pipeline, including genetically modified product candidates GDA-301, GDA-401, GDA-501 and GDA-601, which aim to treat solid-tumor and hematological cancers. These cell therapy candidates utilize CAR, membrane bound- and CRISPR-mediated technologies to increase the NK cell targeting, potency and persistence against hematologic malignancies and solid tumors. Promising new pre-clinical data on GDA-301 and GDA-601 were presented at the International Society for Cell & Gene Therapy Meeting. The data demonstrated that both NAM-enabled cell therapy candidates represented a novel potent and cytotoxic approach in fighting cancer.
Advanced strategic evaluation for omidubicel commercialization, including assessing whether to commercialize omidubicel ourselves or to pursue strategic alternatives to commercialize omidubicel, upon receipt of regulatory approval. The company currently has sufficient cash to fund the company’s operations into mid-2023, excluding the cost of commercializing omidubicel.
"2022 is a potentially transformative year for Gamida Cell as we continue to execute against our clinical and regulatory milestones. We were excited that the FDA accepted our BLA submission with priority review, and if approved, omidubicel will be the first allogeneic advanced stem cell therapy donor source for patients with blood cancers in need of a stem cell transplant. We believe that omidubicel has the potential to change the outlook for patients suffering from blood cancers through improved outcomes, quality of life and increased access for patients who are currently eligible for transplant, but cannot find a match," said Julian Adams, Ph.D., chief executive officer of Gamida Cell. "In addition, the development of our NAM-enabled NK cell therapy candidate, GDA-201, creates an opportunity to potentially bring a new treatment option to tens of thousands of patients with relapsed/refractory lymphoma worldwide. We continue to execute our mission of advancing our broad pipeline of NAM-enabled cell therapies with a curative approach for patients with solid tumors and blood cancers and other serious blood diseases."

Second Quarter and Recent Developments

Omidubicel: Advanced Cell Therapy

BLA accepted by FDA with Priority Review: In August 2022, the FDA accepted for filing Gamida Cell’s BLA for omidubicel for the treatment of patients with blood cancers in need of an allogeneic hematopoietic stem cell transplant. The FDA granted Priority Review for the BLA and has set a PDUFA target action date of January 30, 2023. In parallel, Gamida Cell is preparing for the commercialization of omidubicel in the U.S.
GDA-201: NAM-Enabled NK Cell Therapy

Dosed the first patient in Phase 1/2 study of cryopreserved formulation of GDA-201: In August 2022, Gamida Cell completed the dosing of the first patient in a company-sponsored Phase 1/2 study evaluating a cryopreserved formulation of GDA-201 for the treatment of follicular and diffuse B-cell lymphomas.
The Phase 1 portion of the study is designed as a dose escalation phase to evaluate the safety of GDA-201, and will include patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL), marginal zone lymphoma or mantle cell lymphoma. The Phase 2 expansion phase is designed to evaluate the safety and efficacy of GDA-201 in 63 patients comprised of two patient cohorts, FL and DLBCL. The study will include patients who have relapsed or refractory lymphoma after at least two prior treatments, which may include CAR-T or stem cell transplant.
NAM-Enabled NK Cell Pipeline Expansion

Progressed NAM-enabled genetically modified NK pipeline: Gamida Cell continues to progress its NAM-enabled genetically modified NK pipeline, which utilizes CAR, membrane bound- and CRISPR-mediated technologies to increase targeting, potency and persistence against hematologic malignancies and solid tumors. The company continues to conduct in vitro and in vivo preclinical proof-of-concept studies for these genetically modified NK therapeutic targets which are already showing encouraging results and plans to select the next NK pipeline product candidate for IND enabling studies by the end of 2022. These therapeutic targets include:
GDA-301: Knockout of CISH (cytokine inducible SH2 containing protein) in NK cells using CRISPR/Cas9 in combination with a membrane-bound IL-15/IL-15Ra;
GDA-401: A development candidate with an undisclosed target;
GDA-501: Anti HER2 CAR-engineered NK cells to target solid tumors expressing HER2, based on a single-chain variable fragment of the widely used humanized monoclonal antibody trastuzumab; and
GDA-601: CRISPR Knockout of CD38 on NK cells combined with anti CD38 CAR. CD38 is an established immunotherapeutic target in multiple myeloma, but its expression on NK cells and its further induction during ex vivo NK cell expansion represents a barrier to the development of an anti CD38 CAR-NK cell therapy. Gamida Cell is advancing this program in collaboration with the Dana-Farber Cancer Institute to study the in vitro cytotoxicity of GDA-601 in fresh tumor tissue samples from multiple myeloma patients.
Corporate Updates

Appointed Ivan M. Borrello, M.D. to Board of Directors: Dr. Borrello is an Associate Professor of Oncology at the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins and a renowned physician and author who has made major contributions to better the understanding of immunotherapies and the treatment of hematologic malignancies as well as bone marrow transplant. The Company also announced the resignation of Ofer Gonen from its Board of Directors.
Second Quarter 2022 Financial Results

Research and development expenses were $10.6 million in the second quarter of 2022, compared to $13.4 million in the same quarter in 2021. The decrease was attributable mainly to a $2.4 million decrease in clinical activities relating to the conclusion of our Phase 3 clinical trial and a decrease of $0.4 million in the GDA-201 clinical program.
Commercial expenses were $3.2 million in the second quarter of 2022, compared to $5.0 million in the second quarter of 2021. The decrease was attributable mainly to reducing near-term commercial readiness expenses, as we continued to assess strategic approaches for the commercialization of omidubicel.
General and administrative expenses were $4.3 million in the second quarter of 2022, compared to $3.9 million in the same period in 2021. The increase was mainly due to a $0.9 million increase in professional services expenses, offset by a decrease of $0.5 million in headcount related expenses.
Finance expenses, net, were $0.5 million in the second quarter of 2022, compared to $1.3 million in the same period in 2021. The decrease was primarily due to $0.6 million in non-cash expenses and an increase of $0.2 million in interest income from cash management.
Net loss was $18.6 million in the second quarter of 2022, compared to a net loss of $23.6 million in the second quarter of 2021.
2022 Financial Guidance

Gamida Cell expects that its current cash, cash equivalents and investments will support the company’s ongoing operating activities into mid 2023, excluding the cost of commercializing omidubicel. If we decide to market omidubicel ourselves, we will require substantial additional funding. This cash runaway guidance is based on the company’s current operational plans and excludes any additional funding and any business development activities that may be undertaken. Gamida Cell continues to assess all financing options that support its corporate strategy.

Expected Milestones in 2022 and Early 2023

Omidubicel

PDUFA target action date of January 30, 2023.
NK cell pipeline expansion

Conduct preclinical proof of concept studies of the NAM-enabled, genetically modified NK therapeutic targets
Select pipeline candidate for IND-enabling studies
Conference Call Information

Gamida Cell will host a conference call today, August 15, 2022, at 8:00 a.m. ET to discuss these financial results and company updates. To access the conference call, please register here and be advised to do so at least 10 minutes prior to joining the call. A live webcast of the conference call can be accessed in the "Investors & Media" section of Gamida Cell’s website at www.gamida-cell.com. A replay of the webcast will be available approximately two hours after the event, for approximately 30 days.

About Omidubicel

Omidubicel is an advanced cell therapy candidate developed as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment in comparison to standard umbilical cord blood in an international, multi-center, randomized Phase 3 study (NCT0273029) in patients with hematologic malignancies undergoing allogeneic bone marrow transplant. The Phase 3 study also showed reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. One-year post-transplant data showed sustained clinical benefits with omidubicel as demonstrated by significant reduction in infectious complications as well as reduced non-relapse mortality and no significant increase in relapse rates nor increases in graft-versus-host-disease (GvHD) rates. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the US and EU.

Omidubicel is an investigational stem cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. For more information about omidubicel, please visit View Source

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the potential treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical study data. Preclinical studies have shown that GDA-201 may address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, these data suggest GDA-201 may improve antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the US and EU, which is the patient population that will be studied in the currently ongoing GDA-201 Phase 1/2 clinical trial.

For more information about GDA-201, please visit View Source For more information on the Phase 1/2 clinical trial of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority.

About NAM Technology

Our NAM-enabling technology, supported by positive omidubicel Phase 3 results, is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process

On August 15, 2022 PharmaCyte Biotech, Inc. (NASDAQ: PMCB), a biotechnology company focused on developing cellular therapies for cancer, diabetes and malignant ascites using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that PharmaCyte and Iroquois Master Fund Ltd (Press release, PharmaCyte Biotech, AUG 15, 2022, View Source [SID1234618380]). and its affiliates, the beneficial owners of approximately 6.7% of PharmaCyte’s outstanding shares of common stock, have signed a Cooperation Agreement that includes naming two of Iroquois’ director designees to PharmaCyte’s reconstituted Board of Directors.

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Pursuant to the Agreement, Iroquois’ director designees, Jonathan L. Schechter and Joshua N. Silverman, will join PharmaCyte’s reconstituted Board as independent directors. Jack E. Stover, Daniel S. Farb, and Daniel C. Allen will also join PharmaCyte’s reconstituted Board as independent directors. Existing PharmaCyte directors Kenneth L. Waggoner and Dr. Michael M. Abecassis will complete the 7-member Board.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented, "We are pleased to have reached this constructive agreement with Iroquois which we believe is in the best interest of all shareholders. Our reconstituted Board combines extensive science, operating and capital markets experience that will make PharmaCyte a much stronger company. I would like to thank all of our previous Board members for their numerous and invaluable contributions, including Dr. Matthias Löhr, Dr. Gerald W. Crabtree, Thomas Liquard, Dr. Raymond C.F. Tong and Carlos Trujillo. Each resigned from the Board as part of the Cooperation Agreement after determining that the Cooperation Agreement, including the composition of the new Board, was in the best interest of the Company moving forward.

"We are nearing the end of our process to fulfill the FDA’s requests to enable the clinical hold to be lifted. To date, approximately 90% of the FDA’s requests have been completed or are in process with one major pig study remaining to be completed. We look forward to integrating our new directors’ ideas to drive our continued development and growth as a Nasdaq biotechnology company focused on developing treatments for hard-to-treat diseases like cancer, diabetes, and malignant ascites."

In addition, Iroquois has agreed to certain customary standstill provisions and will support the Board’s full slate of directors at the 2022 Annual Meeting. The complete agreement between PharmaCyte and Iroquois will be included as an exhibit to PharmaCyte’s Current Report on Form 8-K, which will be filed with the U.S. Securities and Exchange Commission.

Richard Abbe, President of Iroquois, concluded, "We appreciate the engagement we have had with PharmaCyte and its shareholders over the last several months. With the appointment of five new highly qualified directors, the majority of whom are direct shareholder representatives, we are confident that the reconstituted Board is well-poised to unlock value for all shareholders."

Biographies for New Board Members:

Daniel C. Allen is an experienced CEO and public company director with significant investment, financial, and operational experience. Currently, Mr. Allen is the Managing Partner of Corona Park Investment Partners, LLC, a firm he founded, and the Executive Chairman on the Board of Directors of Zagg, a global leader in mobile accessories and technologies. He also served as a Director of SharpSpring, Inc. and as the CEO and Director of Evercel, Inc. Prior to forming Corona Park Investment Partners, LLC, Mr. Allen worked for nearly a decade at Bain Capital where he led more than a dozen investments in venture and late-stage technology companies. He also served as a strategy consultant at McKinsey and Company. He received an undergraduate degree in Economics from Harvard College and an M.B.A. from Harvard Business School.

Daniel S. Farb is an experienced investor and public company director. He is currently the Managing Member of Mill Pond Capital. Previously, Mr. Farb served as a Director of Meg Energy Corp. and as a Managing Director at Highfields Capital Management. Mr. Farb has also worked at Goldman, Sachs & Co. in the Mergers & Acquisitions and Principal Investment Groups. Mr. Farb is a graduate of the Harvard Business School, and holds a Bachelor of Commerce Degree from McGill University.

Jonathan L. Schechter is an experienced public company director with expertise in capital allocation and mergers and acquisitions having worked with public companies for over two decades, including ten years of legal experience and fourteen years of investment banking experience. He is currently a partner of The Special Equities Group, a division of Dawson James Securities, Inc., a full-service investment bank specializing in healthcare, biotechnology, technology, and clean-tech sectors. Mr. Schechter is one of the founding partners of The Special Equities Opportunity Fund, a long-only fund that makes direct investments in micro-cap companies. He currently serves on the board of directors of Synaptogenix, Inc., a clinical-stage biopharmaceutical company. Mr. Schechter earned his A.B. in Public Policy/Political Science from Duke University and his J.D. from Fordham University School of Law.

Joshua N. Silverman is currently the Co-Founder and Managing Member of Parkfield Funding LLC and is a former Principal and Managing Partner of Iroquois Capital Management, LLC. Mr. Silverman served as Co-Chief Investment Officer of Iroquois from 2003 until July 2016. From 2000 to 2003, Mr. Silverman served as Co-Chief Investment Officer of Vertical Ventures, LLC, a merchant bank. Prior to forming Iroquois, Mr. Silverman was a Director of Joele Frank, a boutique consulting firm specializing in mergers and acquisitions. Previously, Mr. Silverman served as Assistant Press Secretary to The President of The United States. Mr. Silverman currently serves on the boards of directors of Ayro Inc., MYMD Pharmaceuticals, Inc., Petros Pharmaceuticals, Inc. and Synaptogenix, Inc. Mr. Silverman received his B.A. from Lehigh University.

Jack E. Stover is an experienced CEO, public company director, and investor with extensive knowledge of corporate governance, capital markets strategies and strategic transactions. He is currently CEO of NorthView Acquisition Corp. and has served as CEO and director of multiple life science companies, including Onconova Therapeutics, Interpace Biosciences, and Antares Pharma, Inc. Mr. Stover was formerly a partner with PricewaterhouseCoopers (then Coopers and Lybrand), working in the bioscience industry division in New Jersey. Mr. Stover received his B.A. in Accounting from Lehigh University.

On August 15, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that its Board of Directors has approved a share repurchase program with authorization to repurchase up to $2.0 million of the Company’s outstanding common stock (Press release, PLUS THERAPEUTICS, AUG 15, 2022, View Source [SID1234618379]). The Company intends to fund any share repurchases with available cash.

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"This share repurchase program reflects our continued confidence in our long-term strategy and the strength of the balance sheet and reinforces our commitment to deliver value to shareholders," said Marc H. Hedrick M.D., President and Chief Executive Officer of Plus Therapeutics.

The timing and amount of any shares repurchased will be determined based on the Company’s evaluation of market conditions and other factors, including consent of the Company’s lender. Repurchases may be made from time to time on the open market over the next 12 months, in privately negotiated transactions or by other means, including through the use of trading plans intended to qualify under Rule 10b5-1. Repurchases will be made in accordance with the rules and regulations promulgated by the Securities and Exchange Commission. The Company is not obligated to acquire any shares and the program may be discontinued or suspended at any time.

On August 15, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported statistically significant and clinically meaningful results from the second interim analysis of the key secondary endpoint of overall survival (OS) in the Phase 3 TROPiCS-02 study evaluating Trodelvy (sacituzumab govitecan-hziy) in patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy (Press release, Gilead Sciences, AUG 15, 2022, View Source;Metastatic-Breast-Cancer-Patients-in-the-TROPiCS-02-Study/default.aspx [SID1234618378]). Detailed OS results will be presented at an upcoming medical conference. The safety profile for Trodelvy was consistent with prior studies, and no new safety signals emerged in this patient population.

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"These survival results from the TROPiCS-02 study are important for the breast cancer community and we are encouraged by the potential this may have in helping patients who otherwise have limited alternatives," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "We look forward to discussing these results with global health authorities, as pre-treated HR+/HER2- metastatic disease patients currently have limited treatment options and poor quality of life."

Gilead has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food & Drug Administration (FDA). These data will also be shared with health authorities outside the U.S.

In June 2022, based on the positive primary results from the TROPiCS-02 study presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines)i included a category 2A preferred recommendation for sacituzumab govitecan-hziy for the investigational use in patients with HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy. The TROPiCS-02 study enrolled HR+/HER2- metastatic breast cancer patients, which included patients with HER2-low and IHC 0 status.

TROPiCS-02 is an event driven study with planned analyses based on a pre-specified number of events. This interim analysis was executed based on the pre-specified criteria.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About HR+/HER2- Breast Cancer

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases, or nearly 400,000 diagnoses worldwide each year. Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%. As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.

About the TROPiCS-02 Study

The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test.

More information about TROPiCS-02 is available at View Source

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in more than 35 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

Trodelvy is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

On August 15, 2022 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the second quarter and year-to-date for the period ended June 30, 2022 (Press release, Navidea Biopharmaceuticals, AUG 15, 2022, View Source [SID1234618377]).

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Second Quarter 2022 Highlights and Subsequent Events

Continued enrollment into the Company’s NAV3-33 Phase 3 trial in rheumatoid arthritis ("RA") titled "Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients with Moderate to Severe Active Rheumatoid Arthritis." Enrollment is ongoing across the three currently opened sites.
Announced positive preliminary results from the Company’s ongoing NAV3-32 Phase 2b trial comparing Tc99m tilmanocept imaging to histopathology of joints of patients with active RA. Two non-overlapping classes that align with the fibroid and non-fibroid histological pathotypes were identified, supporting the hypothesis that these classes can be identified by Tc99m tilmanocept imaging.
Received $800,000 from a strategic partner as reimbursement for certain manufacturing and research and development expenses.
The Company’s abstract titled "TAM Targeted Imaging Agents Binding CD206 and Selective Blocking of Off Target Liver Localization" was presented at the Society of Nuclear Medicine and Molecular Imaging Annual Meeting on June 11, 2022 in Vancouver, British Columbia.
The Company’s abstract titled "CD206 Targeted Delivery of Bisphosphonate Payloads Alter Human Macrophage Phenotypes Towards M1-like" was presented at the Tumor Myeloid-Directed Therapies Summit on June 14, 2022 in Boston, MA.
Announced publication of a manuscript titled "Increased Macrophage Specific Arterial Inflammation Relates Uniquely to Non-calcified Plaque and Specific Immune Activation Pathways in People with HIV: A Targeted Molecular Imaging Approach," based on work performed at the Massachusetts General Hospital ("MGH") and Harvard Medical School, Boston MA, and sponsored by the Company. The research, appearing in The Journal of Infectious Diseases (PMID: 35856671), was led by Principal Investigator Steven Grinspoon, MD, Chief of the Metabolism Unit at MGH and Professor of Medicine at Harvard Medical School.
Announced publication of a manuscript titled "Tilmanocept as a novel tracer for lymphatic mapping and sentinel lymph node biopsy in melanoma and oral cancer," based on work performed at the Crown Princess Mary Cancer Centre ("CPMCC") at the University of Sydney, in Sydney, Australia. The research, appearing in the ANZ Journal of Surgery (PMID: 35848587), was led by Principal Investigator Dr. Muzib Abdul-Razak, MBBS, FRACS, FRCSE, MCh., of the Faculty of Medicine, Department of Surgical Oncology and Head and Neck Surgery in the CPMCC at the University of Sydney.
Received notification of issuance of patent from the USPTO for the application titled, "Compounds And Compositions For Treating Leishmaniasis And Methods Of Diagnosis And Treating Using Same" (Patent No. US 11,369,680 B2).
Filed a provisional patent application describing a new degradable linker for dexamethasone and paclitaxel containing Manocept therapeutic constructs. These constructs are being evaluated preclinically for effects on macrophages and in animal models of oncology and inflammatory indications.
Received a Decision of Grant for patent application in Japan for claims related to targeted delivery of a wide range of therapeutic payloads attached to Manocept platform-based constructs using a degradable hydrazone linker.
Closed on a $2.5 million bridge loan from the Company’s Vice Chair of the Board of Directors, John K. Scott, Jr.
Adopted a plan designed to protect the Company’s net operating loss and tax credit carryforwards.
Michael Rosol, Ph.D., Chief Medical Officer for Navidea, said, "The company continues to work diligently to advance the technology in key disease areas, with an emphasis on our RA program. The NAV3-33 Phase 3 and NAV3-32 Phase 2b trials continue to enroll. We are pleased with the preliminary positive results from the NAV3-32 study that thus far support our hypothesis that we can distinguish between fibroid and non-fibroid pathotypes of RA with a single scan." Dr. Rosol continued, "Concurrent with all of this, we continue to make progress in our therapeutics pipeline, and we expect to keep advancing these towards the clinic."

Financial Results

Total net revenues for the second quarter of 2022 were $57,000, compared to $261,000 for the same period in 2021. Total net revenues for the first half of 2022 were $57,000, compared to $385,000 for the same period in 2021. The decrease was primarily due to the 2021 partial recovery of debts previously written off in 2015, the 2021 receipt of reimbursement from Cardinal Health 414, LLC of certain research and development ("R&D") costs, decreased grant revenue related to Small Business Innovation Research grants from the National Institutes of Health supporting Manocept development, and decreased license revenue from transitional sales of Tc99m tilmanocept in Europe.
Research and development expenses for the second quarter of 2022 were $1.7 million, compared to $1.5 million for the same period in 2021. R&D expenses for the first half of 2022 were $2.9 million, compared to $2.7 million for the same period in 2021. The increase was primarily due to increased employee compensation including incentive-based awards and increased recruiting fees, offset by decreases in drug project expenses and regulatory consulting expenses.
Selling, general and administrative ("SG&A") expenses for the second quarter of 2022 were $1.3 million, compared to $1.4 million for the same period in 2021. SG&A expenses for the first half of 2022 were $3.1 million, compared to $3.7 million for the same period in 2021. Decreases in employee compensation including fringe benefits and incentive-based awards, travel, investor relations, general office expenses, facilities costs and franchise taxes were offset by increases in insurance, director fees, losses on the abandonment of certain intellectual property and legal and professional services.
Navidea’s net loss attributable to common stockholders for the second quarter of 2022 was $3.0 million, or $0.10 per share, compared to $2.7 million, or $0.09 per share, for the same period in 2021. Navidea’s net loss attributable to common stockholders for the first half of 2022 was $6.0 million, or $0.20 per share, compared to $5.6 million, or $0.20 per share, for the same period in 2021.
Navidea ended the second quarter of 2022 with $328,000 million in cash and cash equivalents.
The Company’s registration statement on Form S-1 (Registration No. 333-262691) relative to the Company’s current rights offering was declared effective by the Securities and Exchange Commission ("SEC") on August 3, 2022. The prospectus relating to and describing the terms of the rights offering has been filed with the SEC as a part of the registration statement and is available on the SEC’s web site at View Source Copies of the final prospectus for the rights offering may be obtained, when available, from Maxim Group LLC, 300 Park Avenue, New York, NY 10022, Attention Syndicate Department, email: [email protected] or telephone (212) 895-3745.

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

In light of the Company’s pending rights offering, the Company will host a second quarter earnings conference call and business update following the conclusion of the rights offering. The Company will issue a press release announcing the date and time of the earnings conference call.