Ascendis Pharma to Participate in the Oppenheimer 33rd Annual Healthcare Conference

On March 10, 2023 Ascendis Pharma A/S (Nasdaq: ASND) reported that Jan Mikkelsen, President & Chief Executive Officer, and Scott Smith, Executive Vice President & Chief Financial Officer, will participate in a virtual fireside chat at the Oppenheimer 33rd Annual Healthcare Conference on Wednesday, March 15 (Press release, Ascendis Pharma, MAR 10, 2023, View Source [SID1234628512]).

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Details:

Event Oppenheimer 33rd Annual Healthcare Conference
Location Virtual
Date Wednesday, March 15, 2023
Time 12:00-12:30 p.m. Eastern Time / 9:00-9:30 a.m. Pacific Time

A live webcast of the event will be available via the Investors & News section of the Ascendis Pharma website at View Source A webcast replay will also be available on this website shortly after conclusion of the event for 30 days.

Corporate presentation

On March 10, 2023 Anixa Biosciences presenting its corporate presentation (Presentation, Anixa Biosciences, MAR 10, 2023, View Source [SID1234628511]).

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Sermonix Pharmaceuticals Announces Initiation of Phase 3 ELAINE-3 Study of Lasofoxifene Plus Abemaciclib in Pre- and Post-Menopausal Patients with Locally Advanced or Metastatic ER+/HER2- Breast Cancer with an ESR1 Mutation as Detected by Guardant Health’s Guardant360 CDx Liquid Biopsy

On March 10, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast and gynecological cancers harboring ESR1 mutations, and Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the initiation of a registrational Phase 3 clinical study comparing targeted lasofoxifene in combination with the CDK 4/6 inhibitor abemaciclib versus fulvestrant plus abemaciclib in pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation (Press release, Guardant Health, MAR 10, 2023, View Source;and-Post-Menopausal-Patients-with-Locally-Advanced-or-Metastatic-ERHER2–Breast-Cancer-with-an-ESR1-Mutation-as-Detected-by-Guardant-Heal/default.aspx [SID1234628418]).

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This global randomized study will enroll 400 subjects (pre- and post-menopausal women or men) with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation, who have progressed on palbociclib or ribociclib plus an aromatase inhibitor (AI) and up to one line of chemotherapy. Subjects will be randomized 1:1 to receive either lasofoxifene or fulvestrant, and both groups will also receive 150 mg of abemaciclib twice daily. Study subjects will be prospectively screened for an ESR1 mutation using the Guardant360 CDx liquid biopsy, a next generation sequencing (NGS)-based test that detects genomic alterations using circulating tumor DNA from blood. Eli Lilly and Company – which provided abemaciclib (Verzenio) for the ELAINE-2 study – has entered into a new clinical trial collaboration and drug supply agreement with Sermonix and will provide abemaciclib for the ELAINE-3 study.

"The totality of data we have compiled on lasofoxifene to date, including from our completed ELAINE-1 and ELAINE-2 Phase 2 studies, show compelling anti-tumor activity against tumors with increasingly prevalent ESR1 mutations," said Dr. Paul Plourde, vice president for clinical oncology development at Sermonix. "We look forward to further studying lasofoxifene in a large, rigorously designed Phase 3 study, which will include the use of the Guardant360 CDx test to identify patients who have an ESR1 mutation upon progression after first line therapy."

The primary efficacy endpoint is progression-free survival (PFS). Key secondary endpoints include overall response rate (ORR) and overall survival (OS). Additional secondary endpoints to be assessed include clinical benefit rate (CBR), duration of response (DoR), time to disease recurrence (TTR), time to chemotherapy, quality of life, patient reported outcomes on vaginal and sexual health, and safety. Sermonix anticipates dosing the first subject in the first half of 2023.

"The initiation of this Phase 3 combination study is a significant step forward for Sermonix, as we work to develop a novel targeted endocrine treatment option for metastatic breast cancer patients who are post-CDK4/6i with an ESR1 mutation and have limited treatment options that can provide meaningful clinical response," said Dr. David Portman, Sermonix founder and chief executive officer. "We believe the inclusion of the Guardant360 CDx liquid biopsy to accurately identify eligible trial participants will enable us to execute this important study as efficiently as possible. We look forward to dosing the first patients very soon in this area of great unmet medical need."

The Guardant360 CDx test is the first U.S. Food & Drug Administration-approved blood test for comprehensive genomic profiling for all solid tumors. It provides doctors with guideline-complete genomic results in seven days from a simple blood draw to inform treatment decisions.

"We are very pleased to partner with Sermonix on the continued development of lasofoxifene, a promising investigational treatment for select metastatic breast cancer patients who are increasingly resistant to existing endocrine therapies," said Helmy Eltoukhy, co-CEO of Guardant Health. "The Guardant360 CDx test has played a key role in the pivotal trials of several recent precision cancer therapies, and we are excited to partner with Sermonix and support its efforts to address this important and underserved patient population."

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with abemaciclib in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue-selective oral endocrine therapy with additional potential benefits on bone, lipid and vaginal health, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

About Sermonix
Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific and patient-centric oncology products and has currently completed two Phase 2 clinical studies of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes. Paul Plourde, M.D., vice president of oncology clinical development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, Ph.D., chief scientific officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, M.D., is co-founder and chief operating officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, M.M.Sc., Sc.D., chief strategy and development officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, Ph.D., vice president of operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, Ph.D., former president of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. Learn more at SermonixPharma.com.

Utah Company Kuda Therapeutics Awarded $2 Million Grant for Cancer Research

On March 9, 2023 Utah company, Kuda Therapeutics reported the company received a Phase II grant from the National Cancer Institute for $2,050,000 to continue research on novel therapies targeting kidney cancer through the competitive Small Business Innovation Research (SBIR) program (Press release, Kuda Therapeutics, MAR 9, 2023, View Source [SID1234643989]).

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The clear cell subtype of kidney cancer, the most common and aggressive form of this disease, is among the most drug resistant of solid tumors and is uniquely dependent upon the hypoxia-inducible factors (HIF) for its continued growth and progression. Clear cell kidney cancer cells are also exquisitely sensitive to ferroptosis, a newly discovered form of cell death driven by iron accumulation.

Kuda Therapeutics, led by co-founder and CEO, Dr. Mei Yee Koh, and co-founder and CFO, Mr. Travis Ehlinger, identified a molecule that specifically blocks HIF production and induces tumor cell death through ferroptosis. The company’s SBIR Phase II-funded studies will advance the commercial development of this molecule as a new medicine for the treatment of kidney cancer.

"KD061 is a novel first-in-class molecule that inhibits HIF-1/2α and triggers cell death via ferroptosis, thus exploiting two specific vulnerabilities of kidney cancer," said Koh. "This SBIR Phase II grant enables Kuda to advance KD061 towards an Investigational New Drug (IND) filing and first-in-human studies where we can begin to make a difference in the lives of patients."

The company previously received a $560,000 Department of Defense Kidney Cancer Research Program Idea Award (2020-2023) and a $300,000 Phase I SBIR award from the National Cancer Institute (2018-2020). The company worked with the Utah Innovation Center for all three winning proposals.

"The Utah Innovation Center, with their expertise in these grant funding mechanisms’ has provided invaluable assistance to our team in preparing and proofreading these winning proposals. I would encourage other young companies seeking federal funding to utilize this free resource provided by the State of Utah," Koh added.

The Utah Innovation Center is available to assist other Utah companies looking for non-dilutive funding through the federal SBIR/STTR programs. The Innovation Center can be contacted at [email protected].

Entry into a Material Definitive Agreement

On March 9, 2023 Amgen Inc. (the "Company") reported that it has entered into a third amended and restated revolving credit agreement with Citibank, N.A., as administrative agent ("Citibank"), JPMorgan Chase Bank, N.A., as syndication agent, and the other banks party thereto (the "Revolving Credit Agreement"), for a total commitment of $4.0 billion (Filing, Amgen, MAR 9, 2023, View Source [SID1234628510]). Financing under the Revolving Credit Agreement is available for general corporate purposes, including as a liquidity backstop to our commercial paper program. The commitments under the Revolving Credit Agreement may be increased by up to $1.25 billion in the aggregate upon our request at the discretion of the banks and subject to certain customary requirements. The commitments of each bank under the Revolving Credit Agreement have an initial term of five years and may be extended for up to two additional one year periods upon our request at the discretion of the respective banks, subject to certain customary requirements. The Revolving Credit Agreement amends and restates our existing revolving credit agreement dated as of December 12, 2019.

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Advances under the Revolving Credit Agreement will bear interest at an annual rate of, at our option, either (i) Adjusted Term SOFR Rate as defined in the Revolving Credit Agreement (or EURIBOR Rate as defined in the Revolving Credit Agreement for certain advances denominated in Euros) plus between 0.68% and 1.10%, depending on the rating of our senior long-term unsecured debt or (ii) the highest of (A) Citibank’s base commercial lending rate, (B) the overnight federal funds rate plus 0.50%, and (C) one-month Adjusted Term SOFR Rate plus 1.00%, plus between 0.00% and 0.10%, depending on the rating of our senior long-term unsecured debt. We have also agreed to pay a fee for committed funds under the Revolving Credit Agreement, whether used or unused, of between 0.07% and 0.15% per annum depending on the rating of our senior long-term unsecured debt. The Revolving Credit Agreement includes a $300 million sub-limit for issuances of letters of credit.

The Revolving Credit Agreement contains customary affirmative and negative covenants, including limitations on mergers, consolidations and sales of assets, limitations on liens and sales and leasebacks, limitations on transactions with affiliates, and limitations on subsidiary indebtedness. In addition, the Revolving Credit Agreement requires maintenance of a minimum consolidated interest coverage ratio of EBITDA to total interest expense, each on a consolidated basis.

The description of the Revolving Credit Agreement above does not purport to be complete and is qualified in its entirety by reference to the Revolving Credit Agreement, which is filed as Exhibit 10.1 to this report.


Termination of a Material Definitive Agreement.

On December 12, 2022, the Company, Citibank, as administrative agent, Bank of America, N.A. ("Bank of America"), as syndication agent, and Citibank and Bank of America, as lead arrangers and book runners, entered into a bridge credit facility (the "Bridge Credit Facility") (as filed in our Current Report on Form 8-K on December 12, 2022) providing for borrowings of up to $28.5 billion to finance the Company’s acquisition of Horizon Therapeutics plc (the "Acquisition").

The commitments under the Bridge Credit Facility were automatically reduced on December 22, 2022 by the amount of our term loan credit facility (the "Term Loan Credit Facility") (as filed in our Current Report on Form 8-K on December 22, 2022) entered into by the Company, Citibank, as administrative agent, Bank of America, as syndication agent, Citibank, Bank of America, Goldman Sachs Bank USA and Mizuho Bank, Ltd., as lead arrangers and bookrunners, and Goldman Sachs Bank USA and Mizuho Bank, Ltd., as documentation agents, providing for (1) a $2,000,000,000 18-month term loan tranche and (2) a $2,000,000,000 3-year term loan tranche. The commitments under the Bridge Credit Facility were further reduced on March 2, 2023 by the net cash proceeds to the Company from the issuance and sale of senior notes of approximately $23,766,627,500 (the "Senior Note Proceeds"), after deducting underwriters’ discounts and estimated offering expenses payable by the Company (as described in our Current Report on Form 8-K filed on March 2, 2023).

On March 9, 2023, we elected to terminate all remaining outstanding commitments under our Bridge Credit Facility and terminate the Bridge Credit Facility in its entirety in accordance with its terms. In connection with the termination of the Bridge Credit Facility, all accrued and unpaid fees thereunder were paid in full. We elected to terminate the remaining outstanding commitments under our Bridge Credit Facility, as, together with cash on hand, the Senior Note Proceeds, and the commitments under our Term Loan Credit Facility, we have sufficient liquidity to finance the completion of the Acquisition, and the remaining commitments under the Bridge Credit Facility are not needed.