On March 1, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the company’s New Drug Application (NDA) for oral paclitaxel plus encequidar for the treatment of metastatic breast cancer (Press release, Athenex, MAR 1, 2021, View Source [SID1234575854]). The FDA issues a CRL to indicate that the review cycle for an application is complete and that the application is not ready for approval in its present form.

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In the CRL, the FDA indicated its concern of safety risk to patients in terms of an increase in neutropenia-related sequelae on the Oral Paclitaxel arm compared with the IV paclitaxel arm.

The FDA also expressed concerns regarding the uncertainty over the results of the primary endpoint of objective response rate (ORR) at week 19 conducted by blinded independent central review (BICR). The Agency stated that the BICR reconciliation and re-read process may have introduced unmeasured bias and influence on the BICR.

The agency recommended that Athenex conduct a new adequate and well-conducted clinical trial in a patient population with metastatic breast cancer representative of the population in the U.S. The Agency determined that additional risk mitigation strategies to improve toxicity, which may involve dose optimization and / or exclusion of patients deemed to be at higher risk of toxicity, are required to support potential approval of the NDA.

Athenex plans to request a meeting with the FDA to discuss the Agency’s response, engage in a dialogue on the design and scope of a clinical trial to address the FDA’s requirements and align on the next steps required to obtain approval.

"Our clinical and regulatory teams are disappointed by the complete response letter," said Dr. Rudolf Kwan, Chief Medical Officer of Athenex. "We plan to work with the Agency to resolve the issues raised in the CRL and to obtain approval for oral paclitaxel plus encequidar in metastatic breast cancer."

Dr. Johnson Lau, Chief Executive Officer of Athenex, added, "We remain committed to the breast cancer community and will explore the best path forward to obtain regulatory approval. In the interim, we will identify and undertake the appropriate internal organizational adjustments accordingly."

Webcast and Conference Call

Athenex will host a webcast and conference call today Monday, March 1, 2021, at 8 a.m. ET to discuss this regulatory update for oral paclitaxel, as well as the company’s fourth quarter and full year 2020 financial results. The live call may be access by dialing (877) 407 – 0784 (domestic) or (201) 689-8560 (international) fifteen minutes before the conference call begins and reference the passcode 13715950. The live conference call and replay can also be accessed via audio webcast at the Investor Relations section of the Company’s website, located at View Source

On March 1, 2021 Lantheus Holdings, Inc. (NASDAQ: LNTH) (Lantheus), an established leader and fully integrated provider of innovative imaging diagnostics, targeted therapeutics and artificial intelligence solutions to Find, Fight and Follow serious medical conditions, reported the publication of the results of both pivotal studies for PyL, an investigational PET imaging agent that targets prostate-specific membrane antigen (PSMA) (Press release, Lantheus Medical Imaging, MAR 1, 2021, View Source [SID1234575870]). The OSPREY Phase 2/3 trial results have been published online in the Journal of Urology and the CONDOR Phase 3 trial results have been published in the online version of Clinical Cancer Research.

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"The limitations of conventional imaging modalities for prostate cancer create a need for targeted imaging in the initial assessment of high-risk patients as well as in men with early biochemically relapsed disease," said Michael J. Morris, M.D., Prostate Cancer Section Head, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, and lead author of the CONDOR manuscript and senior author on the OSPREY manuscript. "The OSPREY trial data highlighted the high positive predictive value, negative predictive value and specificity of PyL in staging high-risk patients. The CONDOR trial demonstrates its high positive predictive value to accurately locate and identify recurrent cancer early and non-invasively. Assuming FDA approval, physicians will be able to use this clinically meaningful information to identify disease, guide treatment plans, and improve disease management."

Mary Anne Heino, President and Chief Executive Officer of Lantheus added, "We believe these data demonstrate PyL’s clinical benefit and are honored to have our studies published in such well-respected peer-reviewed journals. The results of the OSPREY and CONDOR trials are part of our NDA that is currently under priority review at the FDA for marketing authorization in the United States. We believe PyL has the potential to play an important role in transforming the management of men with high-risk, recurrent or metastatic prostate cancer."

Kenneth J. Pienta, M.D., Director of Research at the James Buchanan Brady Urological Institute and Professor of Urology at Johns Hopkins University School of Medicine, was the lead author of the OSPREY manuscript. The OSPREY publication in the Journal of Urology may be found online here.

Michael J. Morris, M.D., Prostate Cancer Section Head of the Genitourinary Medical Oncology Service and Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center. Was the lead author of the CONDOR manuscript. The CONDOR publication in Clinical Cancer Research may be found online here.

OSPREY Phase 2/3 Trial
The OSPREY trial was designed to assess the diagnostic performance of PyL to detect prostate cancer in pelvic lymph nodes in subjects with high-risk prostate cancer (Cohort A) and confirm distant metastases in subjects with metastatic or recurrent prostate cancer (Cohort B). The primary endpoints for the trial were sensitivity and specificity of PyL PET/CT imaging to detect metastatic prostate cancer within the pelvic lymph nodes relative to histopathology in Cohort A. A key secondary endpoint of the trial was the sensitivity of PyL PET/CT imaging to detect prostate cancer within sites of metastasis or local recurrence relative to histopathology in Cohort B.

In the trial, the diagnostic performance of PyL in detecting disease in pelvic lymph nodes (Cohort A) was compared with histopathology. PyL showed specificity of 96-99%, sensitivity of 31-42%, and PPV of 78-91% meeting the specificity but not the pre-established sensitivity co-primary endpoint. In the metastatic or recurrent prostate cancer setting (Cohort B), PyL exhibited sensitivity of 93-99% and PPV of 81-88% in detecting metastatic lesions. Overall, PyL demonstrated high diagnostic performance in reliably detecting nodal and distant metastatic prostate cancer.

Safety results showed PyL was well tolerated. The most frequent adverse events reported were dysgeusia (2.6%), headache (1.8%), and fatigue (1.3%).

CONDOR Phase 3 Trial
The CONDOR trial was designed to assess the diagnostic performance and clinical utility of PyL in men with biochemically recurrent prostate cancer and uninformative standard imaging. The primary endpoint in the trial was the Correct Localization Rate (CLR) of PyL. CLR is based on positive predictive value, defined as the percentage of patients with a one-to-one correspondence between localization of at least one lesion identified on PyL PET/CT and a composite truth standard. The composite truth is comprised of, in descending priority, histopathology, subsequent correlative imaging findings, or PSA response following radiation therapy. The key secondary endpoint in the trial was the percent of subjects with a change in intended prostate cancer treatment due to PyL imaging results.

The CONDOR trial achieved its primary endpoint, with a CLR of 84.8% to 87.0% among the three blinded independent readers (the lower bound of the 95% confidence intervals ranging from 77.8% to 80.4%). In the key secondary endpoint, 63.9% of patients had a change in intended prostate cancer treatment following review of PyL imaging results. The most frequent changes in intended prostate cancer treatment plans included changing salvage local therapy to systemic therapy, observation to initiating therapy, noncurative systemic therapy to salvage curative local therapy and planned treatment to observation.

Safety results showed PyL was well tolerated. The most frequent adverse event reported was headache, which was reported in four patients (1.9% of the trial population). There was one serious adverse event of hypersensitivity reported as related to the study drug.

About Prostate Cancer
Prostate cancer is the second most common form of cancer affecting men in the United States — an estimated one in eight men will be diagnosed with prostate cancer in their lifetimes. The American Cancer Society estimates that in 2021, 248,530 new cases of prostate cancer will be diagnosed, and 34,130 men will die of the disease. Approximately 3.1 million men in the United States currently count themselves as prostate cancer survivors.1

About PyL
PyL (also known as 18F-DCFPyL) is an investigational fluorinated PSMA-targeted PET imaging agent that enables visualization of localized prostate cancer both localized as well as metastatic to lymph nodes, bone and soft tissue to detect and localize recurrent and/or metastatic prostate cancer. On September 29, 2020, Lantheus submitted a new drug application (NDA) for PyL which was accepted and granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) action date of May 28, 2021.

On March 1, 2021 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages in patients with sepsis, COVID-19 and solid tumors, and Mount Sinai Health System, one of the world’s leading academic health systems, reported a new research collaboration for the development of clinical strategies for Allocetra with checkpoint inhibitors (Press release, Enlivex Therapeutics, MAR 1, 2021, View Source [SID1234575892]). Allocetra is a macrophage-reprogramming immunotherapy product candidate currently in clinical development by Enlivex for the potential treatment of life-threatening immune-mediated diseases.

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Under the strategic collaboration agreement, the parties have agreed to develop and execute a pre-clinical program to investigate the potential synergies between Allocetra and commercially approved checkpoint inhibitor therapies for select solid cancers.

Carlos Cordon-Cardo, M.D., Ph.D., Irene Heinz Given and John LaPorte Given Professor and Chair of the Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Molecular and Cell-Based Medicine at the Icahn School of Medicine at Mount Sinai, commented, "We are impressed with the data supporting the immunotherapeutic effects of Allocetra in preclinical cancer models. The scientific rationale supporting AllocetraTM-checkpoint inhibitor combination therapies is intriguing, as preclinical studies suggest Allocetra may reverse the immunosuppressive tumor microenvironments that often hamper checkpoint inhibitors by reprogramming anti-tumor macrophages to their homeostatic state. We look forward to the further development of Allocetra-checkpoint inhibitor combination therapies through this newly formed collaboration."

A pioneer of the oncologic molecular pathology discipline, Dr. Cordon-Cardo has helped establish a deeper understanding of the mechanisms of human cancers and new targets for cancer diagnosis and therapeutics, enhancing the vision of personalized medicine. Dr. Cordon-Cardo is one of the "Highly Cited Authors" by the Institute of Scientific Information, one of the "Highly Influential Biomedical Researchers" (one of the top 400 over 15,153,100 author identifiers) by the European Society for Clinical Investigation; and one of the top "List of 500 Most Highly Cited Researchers Worldwide," Google Scholar, Citations 101,185; h-index 158; i10-index 521 (Google Scholar-2020). Dr. Cordon-Cardo is the recipient of numerous honors and awards, including "Roll of Honour" of the International Union Against Cancer; Gold Medal of the Swedish Society of Physicians; Distinguished Alumnus Award, Weill-Cornell Graduate School of Medical Science, Cornell University; Fellow, Royal Society of Medicine.

Dror Mevorach, M.D., Chief Medical Officer of Enlivex, commented, "We are excited to collaborate with the distinguished research and clinical teams at Mount Sinai. Allocetra may have a rebalancing effect on the typically immunosuppressive tumor microenvironment, potentially by facilitating the conversion of pro-tumor macrophage populations to anti-tumor populations. Together, we plan to investigate the potential of AllocetraTM to synergistically combine with commercially available checkpoint inhibitors for the treatment of solid tumors."

Oren Hershkovitz, Ph.D., CEO of Enlivex, stated, "The researchers and clinicians at Mount Sinai are world-class and ideal partners as we work toward the realization of Allocetra’s potential. We are pleased with the decision of Mount Sinai to formulate a strategic collaboration with Enlivex for the development of Allocetra as a potentially key component of combination therapies for solid tumors."

Allocetra is currently in clinical development for acute life-threatening immune-mediated diseases such as sepsis and COVID-19. Enlivex recently reported positive top-line results in 21 patients from Phase Ib and Phase II investigator-initiated trials in COVID-19 patients in severe/critical condition. The Company has also previously reported positive results from a Phase Ib investigator-initiated trial in 10 sepsis patients and plans to initiate a controlled, randomized, Phase IIb study in sepsis during the first quarter of 2021.

On March 1, 2021 Oasmia Pharmaceutical AB, an innovation-focused specialty pharmaceutical company, reported that it signed an agreement with Kazia Therapeutics, an Australian oncology-focused biotechnology company, to acquire exclusive global development rights for Cantrixil, a product candidate in development intended for the treatment of ovarian cancer (Press release, Oasmia, MAR 1, 2021, View Source [SID1234575806]). The agreement is the first in a series of planned in-licensing deals and acquisitions to expand Oasmia’s oncology portfolio, leveraging its proven development and regulatory capabilities.

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Oasmia will acquire the license for an upfront cash consideration of $4m, development milestones worth up to $42m and cumulative sales-based royalties. In addition to its promise as stand-alone therapy, Cantrixil has the potential to complement Oasmia’s lead product for ovarian cancer, Apealea, through treatment protocols to be developed. It may also offer synergies with Oasmia’s XR-17 technology platform, which could enhance solubility in various routes of administration.

François Martelet, M.D., CEO of Oasmia, commented: "This agreement is the first step in our transformative ‘string of pearls’ strategy designed to achieve critical mass in Oasmia’s oncology portfolio. Cantrixil is an exciting addition and builds on our development expertise in ovarian cancer. Acquiring rights to Cantrixil, which has established clinical proof of concept, is a major step forward in executing our strategy, and we will continue to leverage our development and partnering expertise to expand our oncology pipeline."

Cantrixil consists of the active molecule, a potent and selective third generation benzopyran SMETI inhibitor named TRXE-002-01, encapsulated in a cyclodextrin. It is believed to target a wide spectrum of cancer cells, including chemotherapy-resistant tumor-initiating cells that are thought to be responsible for disease relapse. In December 2020, Kazia released the top-line results of a Phase I open-label study (NCT02903771) conducted at sites in the USA and Australia. The Phase I study met its primary endpoints, establishing clinical proof of concept, subject to further clinical evaluation and confirmation.

A Phase II study with Cantrixil is expected to be initiated in 2022.

James Garner, CEO and Managing Director at Kazia Therapeutics added: "We are excited by the potential of this novel candidate to target and kill tumor-initiating cells responsible for cancers originating, metastasizing, and relapsing. These slower-growing tumor-initiating cells are often resistant to other types of chemotherapies. Cantrixil has the potential to become a standard front-line agent, complementing the use of platinum therapy in Ovarian cancer patients. Oasmia’s expertise and track record in developing oncology drugs through to approval makes them ideally placed to continue the development of Cantrixil forward to benefit patients who currently have limited treatment options."

Conference call
The company will hold a conference call and an online presentation on March 1, 2021 at 14.00 CET. The call will be hosted by CEO Francois Martelet, and Acting CSO Reinhard Koenig. The presentation will be in English.

On March 1, 2021 The board of directors of Targovax ASA (OSE:TRVX) ("Targovax" or the "Company") reported that it has resolved to increase the share capital of the Company following the completion of an exercise period for vested share options under the Company’s long-term incentive program for employees (Press release, Targovax, MAR 1, 2021, View Source [SID1234575837]). The exercise period for the LTI program commenced on 19 February 2021 at 10:00 hours (CET) and ended on 1 March 2021 at 10:00 hours (CET).

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1. Exercise of options

In total, 29,788 options were exercised, giving the option holders the right to subscribe for 29,788 shares, each with a par value of NOK 0.10, of which:

– 13,000 options were exercised at a subscription price of NOK 5.77 per share;

– 6,250 options were exercised at a subscription price of NOK 6.58 per share; and

– 10,538 options were exercised at a subscription price of NOK 7.74 per share.

2. Resolutions to increase the share capital in Targovax ASA

The Company’s board of directors has on 1 March 2021, in accordance with the authorisation granted by the general meeting on 29 April 2020, resolved to increase the share capital with NOK 2,978.80 by the issuance of 29,788 new shares, each with a par value of NOK 0.10 in order to facilitate the exercise of options.

Accordingly, the new share capital of the Company is NOK 8,656,110.60, divided into 86,561,106 shares, each with a par value of NOK 0.10. The share capital increase will be registered with the Norwegian Register of Business Enterprises (Nw. Foretaksregisteret) as soon as practically possible after the share contribution has been fully paid.