On October 18, 2021 Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it will provide clinical laboratory testing using the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) immunohistochemistry companion diagnostic (Press release, Quest Diagnostics, OCT 18, 2021, View Source,-the-First-Companion-Diagnostic-for-Eli-Lilly-and-Companys-Verzenio-R-abemaciclib-,-a-CDK4-6-Inhibitor-for-Certain-People-with-HR-HER2-High-Risk-Early-Breast-Cancer [SID1234591458]).

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On October 13, the U.S. Food and Drug Administration (FDA) approved Eli Lilly and Company’s Verzenio (abemaciclib), in combination with endocrine therapy (tamoxifen or an aromatase inhibitor), for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test. Ki-67 is a marker of cellular proliferation. Verzenio is the first and only CDK4/6 inhibitor approved for this patient population.

In aligned actions, the FDA also granted pre-market approval to Ki-67 IHC MIB-1 pharmDx (Dako Omnis) from Agilent Technologies, Inc. as a companion diagnostic for Verzenio. Quest is the first laboratory to have validated the test in conjunction with Agilent. Since the validation of an IVD assay can take weeks, Quest is committed to providing the test as soon as possible, with plans to make it nationally available by the end of the month.

"The imminent addition of Ki-67 IHC MIB-1 pharmDx (Dako Omnis) testing to our oncology menu underscores our commitment to providing precision medicine innovations with potential to improve outcomes for patients with cancer," said Kristie Dolan, General Manager, Oncology Franchise, Quest Diagnostics. "It also reflects our ability to create value-producing relationships across healthcare, building on our long-standing precision medicine collaboration with Agilent."

Quest Diagnostics is a leading diagnostics services provider in oncology and genetics. Covering the breadth of diagnostic services, from screening and diagnosis to treatment selection, prognosis and monitoring recurrence, the company’s expertise spans nearly all cancers, including breast, thyroid, lung cancer, colorectal, prostate, cervical, multiple myeloma and leukemia/lymphoma, among others.

About Early Breast Cancer and Risk of Recurrence
It is estimated that 90 percent of all breast cancers are detected at an early stage. Although the prognosis for HR+ HER2- EBC is generally positive, 20 percent of patients will experience recurrence potentially to incurable metastatic disease.1 Risk of recurrence is greatest within the initial two to three years post-diagnosis, particularly in patients with node-positive, high risk EBC.2 Factors associated with high risk of recurrence include: positive nodal status, large tumor size (≥5 cm), high tumor grade (Grade 3), and high rate of cellular proliferation [Ki-67 score (≥20%)].3

Node-positive means that cancer cells from the tumor in the breast have been found in the lymph nodes in the armpit area. Although the breast cancer is removed through surgery, the presence of cancer cells in the lymph nodes signifies that there is a higher chance of the cancer returning and spreading.

About Breast Cancer
Breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer worldwide in females, according to GLOBOCAN. With approximately 685,000 deaths in 2020, breast cancer is the fifth-leading cause of cancer death worldwide.4 In the U.S., it is estimated that there will be 281,550 new cases of breast cancer in 2021.5 Approximately 70 percent of all breast cancers are of the HR+ HER2- subtype.5

About Verzenio (abemaciclib)
Verzenio abemaciclib is a targeted treatment known as a CDK4/6 inhibitor. Verzenio is a non-chemotherapy oral tablet.

Verzenio works inside the cell to block CDK4/6 activity and help stop the growth of cancer cells, so they may eventually die (based on preclinical studies).* Cyclin-dependent kinases (CDK)4/6 are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4/6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio is Lilly’s first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.

INDICATIONS FOR VERZENIO
Verzenio (abemaciclib) in combination with endocrine therapy (ET) is indicated for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test.

Verzenio is indicated for the treatment of HR+ HER2- advanced or metastatic breast cancer:

in combination with an aromatase inhibitor for postmenopausal women, and men, as initial endocrine-based therapy
in combination with fulvestrant for adult patients with disease progression following endocrine therapy
as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting
Please see full Prescribing Information for Verzenio.

On October 18, 2021, PDS Biotechnology Corporation reported its corporate presentation (Presentation, PDS Biotechnology, OCT 18, 2021, View Source [SID1234591457]).

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On October 18, 2021 Novo Nordisk reported that it initiated a share repurchase programme in accordance with Article 5 of Regulation No 596/2014 of the European Parliament and Council of 16 April 2014 (MAR) and the Commission Delegated Regulation (EU) 2016/1052 of 8 March 2016 (the "Safe Harbour Rules") (Press release, Novo Nordisk, OCT 18, 2021, View Source [SID1234591456]). This programme is part of the overall share repurchase programme of up to DKK 18 billion to be executed during a 12-month period beginning 3 February 2021.

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Under the programme initiated 4 August 2021, Novo Nordisk will repurchase B shares for an amount up to DKK 3.3 billion in the period from 5 August 2021 to 1 November 2021.

Since the announcement 11 October 2021, the following transactions have been made:

With the transactions stated above, Novo Nordisk owns a total of 21,784,947 B shares of DKK 0.20 as treasury shares, corresponding to 0.9% of the share capital. The total amount of A and B shares in the company is 2,310,000,000 including treasury shares.

Novo Nordisk expects to repurchase B shares for an amount up to DKK 18 billion during a 12- month period beginning 3 February 2021. As of 15 October 2021, Novo Nordisk has since 3 February 2021 repurchased a total of 22,977,781 B shares at an average share price of DKK 505.36 per B share equal to a transaction value of DKK 11,611,964,393.

On October 18, 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 interim results from its U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma (STS) lung metastases, which documented preliminary clinical activity for Annamycin (Press release, Moleculin, OCT 18, 2021, View Source [SID1234591455]).

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The Phase 1b/2 study is a U.S. multi-center, open-label, single-arm study that in Phase 1b will determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) and safety of Annamycin. The Phase 2 portion of the study will explore the efficacy of Annamycin as a single agent for the treatment of subjects with STS with lung metastases, who have failed prior chemotherapy, and for whom new chemotherapy is considered appropriate. A minimum of 3 subjects will be enrolled in each of up to 6 cohorts of the Phase 1b portion of the study, or until an MTD is identified, whichever comes first. A maximum of 25 subjects will be enrolled at the RP2D to further evaluate efficacy.

"To witness the activity of Annamycin in the treatment of STS lung metastases, even this early in a Phase 1 trial, we believe is encouraging. Four of the five patients that have completed scans to date demonstrated a response to treatment, including three with extended and, in one case, continuing stable disease and one patient with a substantial (>30%) reduction in tumor size. These interim data bolster our optimism about the potential for Annamycin to address the limitations with the current standard-of-care treatment options for STS lung metastases. Ultimately, we believe Annamycin has the potential to bring a new and effective treatment option to patients with a significant unmet need. With these data now in hand, we are cautiously optimistic as we begin patient enrollment and dosing in the next cohort," commented Walter Klemp, Chairman and CEO of Moleculin.

Mr. Klemp added, "We are also encouraged by the pace of recruitment so far in this trial. To have completed 2 full cohorts in just the first 4 months of the study with only one site open is faster than we would have expected, especially for a rare disease like STS lung metastases. And, with more sites joining the study before the end of the year, we believe there is the potential for this pace of recruitment to continue or even accelerate."

"As with all of the patients treated so far in our acute myeloid leukemia trials, no patients in this STS trial have exhibited any signs of cardiotoxicity," Mr. Klemp concluded. "This is an important point because, even though anthracyclines are considered a cornerstone chemotherapy for many types of cancer, including STS lung metastases, all currently approved anthracyclines are significantly cardiotoxic. Annamycin was designed to overcome this problem and we believe it has the potential to become the first non-cardiotoxic anthracycline approved for use. This could not only reduce the risk of many current anthracycline treatment regimens, but it could also enable longer treatment periods without cardiac risk."

The summary of interim data from the first two cohorts of the study are as follows:

First Cohort:

One subject is ongoing and is currently in cycle 5 of treatment and expects to enter cycle 6 of treatment at the end of this month. The end of cycle 4 scan revealed stable disease.
One subject discontinued after 6 cycles (4.5 months) due to progressive disease. However, stable disease was maintained up to that point.
One subject discontinued after cycle 1. The end of study scan was performed, and stable disease was observed. The subject was discontinued from the study because cycle 2 treatment was delayed greater than 6 weeks from the prior dosing.
Second Cohort:

One subject is ongoing and is currently in cycle 3 of treatment. The end of cycle 2 scan revealed partial response (PR, >30% reduction in tumor size).
One subject was discontinued from the study after 2 cycles after the end of cycle scan revealed progressive disease.
One subject received one cycle of treatment to-date and discontinued treatment for reasons unrelated to Annamycin. The end of study scans are scheduled in the coming weeks.
These are interim data and should be considered preliminary and subject to change.

The Company has now opened enrollment in the third cohort of the Phase 1b portion of the study. Three subjects minimum (6 maximum) for each dosing cohort will be enrolled until a maximum tolerated dose is identified. Therefore, up to 36 subjects may be enrolled in the Phase 1b portion of the study.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of STS lung metastases, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

Study Design

In Phase 1b, Annamycin is administered as an intravenous (IV) infusion over 2 hours on Day 1, followed by 20 days off (1 cycle = 21 days). Subjects visit the study site every 21 days (±3 days) at which time safety monitoring, including adverse events (AEs), a physical examination, laboratory evaluations (clinical chemistry, complete blood count), vital signs, weight measurements, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiograms (ECGs) will be performed, followed by an IV infusion of study drug. Additional laboratory evaluations (clinical chemistry, complete blood count) will be performed at 7 days (± 3 days) and 14 days (± 3 days) from the Annamycin infusion for additional safety monitoring during each cycle. Cardiac function will be followed by echocardiogram (ECHO) scans at screening, at the end of the first two cycles and then every other cycle thereafter, at the end of treatment visit, and if feasible, during follow up at 6 months (±1 month) and 1 year (±1 month) after study drug discontinuation. As long as the Investigator considers that the benefits of treatment with Annamycin continue to outweigh the risks, treatment will continue every 21 days until tumor progression is observed or unacceptable toxicity occurs.

Tumor response is monitored every 6 weeks (±1 week) from Cycle 1 Day 1 during treatment, at the End of Treatment visit, and then every 3 months (±1 month) until disease progression using RECIST criteria. Those subjects who leave the study after a maximum response is achieved and who do not start another therapy will be followed every 3 months (±1 month) for progression-free survival (PFS). If a subject receives further therapy after discontinuing from the study, they will only be followed for overall survival (OS) and if feasible, follow-up ECHO scans at 6 months (±1 month) and 1 year (±1 month) after study drug discontinuation.

About Annamycin

Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in recently conducted human clinical trials for the treatment of acute myeloid leukemia (AML), and 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.

On October 18, 2021 Lipocine Inc. (NASDAQ: LPCN), a clinical-stage biopharmaceutical company focused on metabolic and endocrine disorders, reported it has entered into an exclusive licensing agreement with Antares Pharma, Inc. to commercialize TLANDO in the United States (Press release, Lipocine, OCT 18, 2021, View Source [SID1234591454]). TLANDO is an oral testosterone product for testosterone replacement therapy ("TRT") in adult males indicated for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired).

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As previously announced, the U.S. Food and Drug Administration ("FDA") granted tentative approval to TLANDO. Upon the expiration of the exclusivity period granted to Clarus Therapeutics, Inc., with respect to its drug, JATENZO, under the Hatch-Waxman Act, which expires on March 27, 2022, TLANDO will be eligible for final approval. The FDA has affirmed the NDA resubmission for final approval will be a Class 1 resubmission which includes a two-month FDA review goal period.

Under the terms of the agreement, Lipocine will receive an immediate upfront cash payment of $11.0 million and, subject to certain conditions, an additional $5.0 million licensing payment in January 2025 and another $5.0 million licensing payment in January 2026. Lipocine will also be entitled to receive sales-based commercial milestone payments totaling up to $160.0 million based on TLANDO net sales and, if Antares Pharma exercises its option, TLANDO XR sales, in addition to tiered royalty payments at rates ranging from the mid-teens to up to 20% on net sales of TLANDO. Lipocine retains all rights for ex-US territories, and non TRT indications for TLANDO. Under the agreement, Antares Pharma will undertake all commercialization, post-marketing obligations, and sourcing of TLANDO in the U.S.

In addition, Lipocine has granted Antares Pharma an option to license, on or before March 31, 2022, TLANDO XR, a next-generation, potential once-daily oral product candidate for TRT, in the U.S. TLANDO XR met primary and secondary regulatory end points for TRT in an earlier Phase 2 clinical study. Upon exercise of the TLANDO XR option, Lipocine is entitled to receive an additional $4.0 million in license fees, clinical and regulatory milestone payments of up to an aggregate of $35.0 million, and tiered royalties on net sales at rates ranging from the mid-teens to up to 20%. Antares Pharma will be responsible for development costs, regulatory filings, commercialization, and post-marketing commitments for TLANDO XR.

"We are very pleased to be partnering with Antares Pharma, a strong market leader with one of the largest sales forces in the TRT space," said Dr. Mahesh Patel, Chairman, President and Chief Executive Officer of Lipocine. Dr. Patel further stated, "Our agreement with Antares Pharma demonstrates our commitment to ensure efficient and effective patient access to TLANDO in the U.S. We are confident in Antares Pharma’s capabilities, given its established marketing experience and demonstrated success in the TRT space. Consistent with our current core competency, this agreement allows us to focus diligently on progressing our innovative pipeline candidates with the goal of serving patients with serious unmet needs."