On December 7, 2021 SynDevRx, Inc., a clinical-stage biotechnology company leading the development in treatments for obesity-accelerated cancers, reported a research collaboration with Australia’s Queensland University of Technology (Press release, SynDevRx, DEC 7, 2021, View Source [SID1234596566]). The collaboration with Professor Colleen Nelson, PhD, and her team will study the role of methionine aminopeptidase 2 (MetAP2) inhibition in tumor growth in castration resistant and other treatment resistant forms of prostate cancer.

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Obesity and systemic metabolic dysfunction like pre-diabetes and type 2 diabetes are known to make many solid tumors more aggressive, including prostate cancer. MetAP2 inhibitors, such as evexomostat (SDX-7320), have been clinically shown to improve systemic metabolic hormone dysregulation1 and to possess direct anti-tumor, anti-metastatic and anti-angiogenic properties2. This combination of attributes may be well suited to sever the link between metabolic dysfunction and cancer, and may prove to be effective in treating advanced prostate cancer in combination with standard-of-care therapies.

Professor Nelson is the founder and executive director of the Australian Prostate Cancer Research Centre – Queensland (APCRC-Q) and Chair of Prostate Cancer Research at Queensland University of Technology (QUT). APCRC-Q, is one of the leading global research facilities investigating the connection between prostate cancer and dysregulated metabolic hormones and pathways, and how these affect prostate cancer progression and metastasis. "The downstream effects of obesity change the tumor microenvironment in ways highly favorable to prostate cancer recurrence, progression and metastasis. Hyperleptinemia and hyperinsulinemia are well-established, negative side effects of androgen deprivation therapy (ADT) and other treatments that block the androgen axis in prostate cancer. The APCRC-Q has been investigating this relationship using targeted drugs in preclinical models that inhibit metabolic pathways induced by ADT, through tumor promoting pathways activated systemically, and through direct tumor cell adaptation," said Colleen Nelson, PhD, lead investigator. "We’re very excited to study SynDevRx’s SDX-7320 inhibition of MetAP2 in our well-vetted models of treatment resistant advanced prostate cancer models."

The APCRC-Q team’s research focuses on pathways activated by ADT, including alterations in metabolism that are druggable with novel targeted agents. They recently showed that pharmacological blockade of leptin receptor or the activation of adiponectin signaling was efficacious in significantly reducing tumor burden and in delaying progression to castration resistance in animal models. The APCRC-Q team has also been targeting metabolic pathways directly through mitochondrial activity or lipid synthesis in models of CRCP and ENZ resistance.

"Professor Nelson team’s work has clearly demonstrated the central role that leptin and adiponectin play in the feedback loop of androgen deprivation and results in the emergence of treatment resistance," said Peter Cornelius, PhD, senior director of translational research at SynDevRx. "Her lab has some of the best models for studying the deleterious effects of inhibition of the androgen receptor axis in prostate cancer, identifying mechanisms of resistance and then targeting those proteins driving the resistance in pre-clinical prostate cancer models. Given our clinical results showing evexomostat (SDX-7320) significantly lowers leptin and increases adiponectin in late-stage cancer patients, we’re thrilled to work with Professor Nelson and her expert team on testing the potential beneficial effects that SDX-7320/MetAP2 inhibition could play in these validated models."

"SynDevRx is establishing global collaborations with leading research institutions focused on the downstream effects that obesity and dysregulated metabolic hormones have on cancer progression and metastasis. We invite other researchers to work with us as we untangle these complex and critical interactions between cancer and dysregulated metabolic hormones," said SynDevRx’s co-founder and Chief Business Officer James Shanahan.

(Proietto et al., Diabetologia 2018 Sep;61(9):1918-1922)
(Mann-Steinberg et al., "TNP-470: The Resurrection of the First Synthetic Angiogenesis Inhibitor." (2008).)
About SDX-7320

SynDevRx believes that evexomostat (SDX-7320) is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin/leptin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, improvements in key lipids, and inhibition of the important angiogenic proteins bFGF and VEGF-C, as was demonstrated in a Phase 1 clinical study in late-stage cancer patients. In preclinical studies, evexomostat also directly inhibited multiple cell cycle signaling pathways, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed obesity-induced immune suppression within the tumor micro-environment of tumor-bearing obese mice. Evexomostat (SDX-7320) is being developed for use in combination with clinically indicated standard-of-care cancer therapies for breast and prostate cancers.

On December 7, 2021 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the expansion of Dr. F. Joseph Daugherty’s role to include the critical responsibility of Medical Monitor of the Phase III clinical trial and a long-term agreement to serve as Chief Medical Officer (Press release, Greenwich LifeSciences, DEC 7, 2021, View Source [SID1234596563]).

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Dr. Daugherty commented, "I look forward to supporting the GLSI-100 clinical trials as Medical Monitor. While GP2 has been shown to be both effective and safe in the Phase IIb trial, we will maintain our vigilance in the larger Phase III trial. The mild local and systemic reactions observed in the Phase IIb trial have served to further validate the immune response and mechanism of action of GP2, thus requiring the balancing of dosing to ensure that local and systemic reactions are tolerable and safe, yet still sufficiently robust enough to lead to the prevention of metastatic breast cancer recurrence."

CEO Snehal Patel added, "We are very excited that Dr. Daugherty is expanding his role with a very significant commitment to serve as medical monitor of our upcoming and future clinical trials as we seek to expand GP2’s potential to all HER2 positive breast cancer patients and to explore HER2 low breast cancer and other HER2 expressing cancers. While we have not seen any serious adverse events in the 138 patients we have treated to date across four clinical trials attributable to GP2 immunotherapy, Dr. Daugherty’s responsibility to oversee the safety of our Phase III trial will be a key component of our regulatory strategy in this potential single registration trial."

Dr. Daugherty has over 40 years of experience in managing and overseeing biotechnology and biomedical projects. He served first as President and recently as Chief Executive Officer, Chief Medical Officer, and the Chairman of the board of directors of Eleos, Inc., a clinical-stage, private biotech company focused on anti-sense technology in hematologic cancers. In addition to being an officer and director, Dr. Daugherty has served in various other capacities, including as a management consultant to over 20 public and private biomedical companies including Dupont, Inc, and as President of ConAgra’s biotech division. He received a BA in Biology from Washington University, a MD from the University of Nebraska, and a MS in Industrial Administration from Carnegie Mellon University.

About FLAMINGO-01 and GLSI-100

The Phase III clinical trial will be called FLAMINGO-01 and the combination of GP2 + GM-CSF will be called GLSI-100. The Phase III trial is comprised of 2 blinded, randomized, placebo-controlled arms for approximately 500 HLA-A*02 patients and 1 open label arm of up to 100 patients for all other HLA types. An interim analysis has been designed to detect a hazard ratio of 0.3 in IDFS, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. The trial is currently being registered on clinicaltrials.gov and the link and trial identifier will be published shortly. For future updates about FLAMINGO-01 please visit the Company’s clinical trial tab at View Source

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On December 7, 2021 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that the first patient was enrolled in an expansion arm of the GLORIA clinical trial of NOX-A12 in MGMT unmethylated brain cancer (glioblastoma, GBM) (Press release, NOXXON, DEC 7, 2021, View Source [SID1234596561]). The patient has received their first week of treatment of NOX-A12 (600 mg/week) and the VEGF inhibitor bevacizumab combined with radiotherapy.

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The GLORIA Phase 1/2 clinical trial evaluates the safety and efficacy of NOX-A12 combined with radiotherapy. In three expansion arms, the synergistic benefit of NOX-A12 with other therapeutic settings will be evaluated:

Arm A: NOX-A12 with radiotherapy in patients with complete tumor resection
Arm B: NOX-A12 with radiotherapy and bevacizumab in patients with incomplete tumor resection
Arm C: NOX-A12 with radiotherapy and anti-PD-1 in patients with incomplete tumor resection.

Each expansion arm plans to evaluate 6 patients.

Aram Mangasarian, CEO of NOXXON, commented: "After the compelling results seen with NOX-A12 in glioblastoma patients in the GLORIA trial when combined only with radiotherapy, we are excited to move forward and explore additional treatment combinations that will potentially bring further benefits to these very difficult to treat patients. At this point, we are planning to prioritize recruitment to the bevacizumab and pembrolizumab arms and look forward to seeing the results."

Expansion arms A and B have already been approved by the German Federal Institute for Drugs and Medical Devices (BfArM, Bundesinstitut für Arzneimittel und Medizinprodukte), while the third arm is still under review. The expansion arms aim at providing additional clinical data to support the design of the planned pivotal trial and discussions with the regulatory agencies.

On December 7, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported that it will host a conference call and webcast to review the clinical status and provide an update on its pipeline programs (Press release, Harpoon Therapeutics, DEC 7, 2021, View Source [SID1234596560]).

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The live call/webcast will take place at 4:30 p.m. ET / 1:30 p.m. PT on December 13, 2021 and can be accessed by dialing (866) 951-6894 for domestic callers and (409) 216-0624 for international callers with conference ID code number 2760075. A webcast of the live call will be available online in the investor relations section of the Harpoon website at www.harpoontx.com. A replay of the webcast will be available shortly after the live event and can be accessed at the same weblink.

On December 7, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that priced an $8.0 billion public offering of five series of senior unsecured notes (collectively, the "notes") (Press release, Merck & Co, DEC 7, 2021, View Source [SID1234596558]). The notes include:

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$1.5 billion of 1.700% notes due 2027 (the "2027 notes")

$1.0 billion of 1.900% notes due 2028 (the "sustainability notes")

$2.0 billion of 2.150% notes due 2031 (the "2031 notes")

$2.0 billion of 2.750% notes due 2051 (the "2051 notes")

$1.5 billion of 2.900% notes due 2061 (the "2061 notes")

Merck intends to use the net proceeds from the offering of the 2027 notes, the 2031 notes, the 2051 notes and the 2061 notes for general corporate purposes, including without limitation the repayment of outstanding commercial paper borrowings (including commercial paper borrowings in connection with Merck’s acquisition of Acceleron), and other indebtedness with upcoming maturities. Merck intends to allocate an amount equal to the net proceeds of the offering of the sustainability notes to finance or refinance, in whole or in part, eligible projects. The offering is expected to close on Dec. 10, 2021, subject to customary closing conditions. BofA Securities, Inc., Barclays Capital Inc., Credit Suisse Securities (USA) LLC, Deutsche Bank Securities Inc. and Goldman Sachs & Co. LLC are acting as the joint book-running managers for the offering.

The offering of the notes is being made pursuant to an effective shelf registration statement (including a base prospectus) filed with the Securities and Exchange Commission (the "SEC"). The offering may be made only by means of a prospectus and related prospectus supplement, copies of which may be obtained by calling BofA Securities, Inc. toll-free at 1-800-294-1322, Barclays Capital Inc. toll-free at 1-888-603-5847, Credit Suisse Securities (USA) LLC toll-free at 1-800-221-1037, Deutsche Bank Securities Inc. toll-free at 1-800-503-4611 or Goldman Sachs & Co. LLC toll-free at 1-866-471-2526. An electronic copy of the registration statement and prospectus supplement, together with the base prospectus, is available on the SEC’s website at www.sec.gov.

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