On August 29, 2023 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported that the company is scheduled to present at the Morgan Stanley 21st Annual Global Healthcare Conference on Tuesday, September 12, 2023, at 7:30 a.m. EST (Press release, Agios Pharmaceuticals, AUG 29, 2023, View Source [SID1234634739]).

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A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. A replay of the webcast will be archived on the company’s website for at least two weeks following the presentation.

On August 29, 2023 y Pharmaxis Ltd (ASX: PXS) reported publication in the prestigious journal Nature Cancer of preclinical results showing pan‐Lysyl Oxidase (pan‐LOX) inhibitor PXS‐5505 increases survival by 35% compared to chemotherapy treatment alone in the treatment of pancreatic ductal adenocarcinomas (Press release, Pharmaxis, AUG 29, 2023, View Source;utm_campaign=PXS%20Cancer%20Drug%20Shows%20Increased%20Survival%20in%20Preclinical%20Models%20of%20Aggressive%20Pancreatic%20Cancer&utm_content=PXS%20Cancer%20Drug%20Shows%20Increased%20Survival%20in%20Preclinical%20Models%20of%20Aggressive%20Pancreatic%20Cancer+CID_c1c2ee092add41ee681fc9a7144e424a&utm_source=Campaign%20Monitor&utm_term=View%20Full%20Media%20Release [SID1234634721]).

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Research in mouse models, led by a team at the Garvan Institute of Medical Research in Sydney, Australia, also showed PXS‐5505 combined with chemotherapy reduced the spread of the cancer to other organs such as the liver by 45%. Pancreatic ductal adenocarcinoma is one of the most aggressive forms of pancreatic cancer with a five‐year survival rate of less than 10%.

Associate Professor Thomas Cox, head of the Matrix & Metastasis Lab at Garvan and senior author of the study, said, "The preclinical validation of this first‐in‐class anti‐fibrotic drug marks a major milestone in the quest to overcome the significant challenges in treating pancreatic cancer and brings hope to patients and their families."

Pharmaxis Chief Executive Gary Phillips said, "We have already seen very promising early results in a phase 2 trial with patients that have the bone marrow cancer myelofibrosis. This ground‐breaking research stems from a long collaboration with the team of high calibre researchers at the Garvan Institute and provides exciting new evidence that PXS‐5505 may also have a role as a therapy to improve the effect of current chemotherapy drugs in solid tumours like pancreatic cancer and extending the life of patients."

PXS‐5505 is an anti‐fibrotic pan‐Lysyl Oxidase (pan‐LOX) inhibitor that has completed long‐term toxicity studies and Phase 1a and 1b clinical trials demonstrating a well‐tolerated drug that effectively inhibits all enzymes in the lysyl oxidase family that are involved in fibrosis. Pancreatic cancer is often diagnosed at an advanced stage, which means that chemotherapy is usually the only treatment option available. Many pancreatic cancers develop chemotherapy resistance soon after treatment starts, which contributes to the poor survival of patients. Part of this resistance is driven by tumour fibrosis forming a mesh of scar tissue within and around pancreatic tumours that in turn reduces the effectiveness of chemotherapy drugs.

"PXS‐5505 returns the tumour microenvironment to a more "normal" state by reducing fibrosis and decreasing tumour stiffness," said Dr Jessica Chitty, Senior Research Officer at Garvan and first author of the study. "This allows chemotherapy drugs to penetrate the tumours more easily, work more effectively, and destroy more cancer cells.

The Nature Cancer publication can be seen here: View Source;023‐ 00614‐y. It adds to the body of pre‐clinical evidence published from other Pharmaxis collaborations with leading scientific institutions in the last year on the role of LOX enzymes in disease including:

 Inhibition of lysyl oxidases synergizes with 5‐azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies; Nature Communications 2023 View Source;023‐37175‐8

 Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis, Nature Communications 2022 View Source;022‐33148‐5

 Pan‐Lysyl Oxidase Inhibitor PXS‐5505 Ameliorates Multiple‐Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis, International Journal of Molecular Sciences 2022 View Source

On August 28, 2023, Biogen Inc. (the "Company") reported to have entered into a Credit Agreement with JPMorgan Chase Bank, N.A. ("JPMorgan"), as Administrative Agent, and the lenders party thereto (the "Credit Agreement") (Filing, 8-K, Biogen, AUG 28, 2023, View Source [SID1234634831]). The Credit Agreement provides for a $1.5 billion unsecured term loan facility, comprised of a $750 million 364-day tranche ("Tranche A") and a $750 million three-year tranche ("Tranche B" and collectively, the "Term Facility").

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Borrowings under the Term Facility will be available to the Company to (a) pay a portion of the consideration for the previously announced acquisition by the Company of Reata Pharmaceuticals, Inc. ("Reata") pursuant to an Agreement and Plan of Merger among the Company, River Acquisition, Inc. ("Merger Sub") and Reata (the "Merger Agreement") pursuant to which, and upon the terms and subject to the conditions set forth therein, Merger Sub will be merged with and into Reata (the "Merger"), with Reata surviving the Merger as a wholly-owned subsidiary of the Company, (b) repay indebtedness and other amounts outstanding under certain of Reata’s existing funding agreements and (c) pay fees and expenses in connection with the transactions described in the foregoing paragraphs (a) and (b).

Loans under the Credit Agreement will be denominated in dollars and will bear interest at a rate per annum equal to (i) Term SOFR, subject to a floor of 0.00% per annum, plus an applicable margin ranging from 1.250% to 1.625% based on the ratings of the Company’s non-credit enhanced, senior unsecured long-term debt, as determined by Standard & Poor’s and Moody’s (the "Debt Ratings") or (ii) at the Company’s option, a Base Rate equal to the highest of (a) the greater of the Federal Funds Rate or a composite overnight rate determined by the Federal Reserve Bank of New York (the "NYFRB") and published on the NYFRB’s website plus, in each case, 0.50%, (b) the Prime Rate and (c) Term SOFR for a one month interest period plus 1%, subject to a floor, in each case, of 0.00% per annum (the "Base Rate"), plus an applicable margin ranging from 0.250% to 0.625% based on the Company’s Debt Ratings.

In addition to paying interest on any outstanding principal under the Term Facility, the Company will pay a commitment fee in respect of the unutilized commitments thereunder ranging from 0.100% to 0.175% per annum based on the Company’s Debt Ratings.

Loans under the Credit Agreement shall be drawn in a single drawing on the closing date of the Merger (the "Funding Date"), following which any undrawn commitments under the Term Facility shall automatically terminate. The funding of the Term Facility is contingent on the satisfaction of customary conditions, including the consummation of the Merger in accordance with the terms set forth in the Merger Agreement. The Term Facility will terminate and all amounts outstanding thereunder shall become due and payable (i) in the case of Tranche A, 364 days after the Funding Date and (ii) in the case of Tranche B, 3 years after the Funding Date. Under the Term Facility, voluntary prepayments are permitted, in whole or in part, in minimum amounts without premium or penalty, other than customary breakage costs.

The Credit Agreement contains customary representations and warranties, affirmative and negative covenants and events of default that are, in each case, substantially similar to the equivalent terms of that certain Credit Agreement, dated as of January 28, 2020 (as amended, restated, amended and restated, supplemented and/or otherwise modified prior to the date hereof) among the Company, the lenders party thereto and Bank of America, N.A., as administrative agent.

The Credit Agreement also includes a financial covenant requiring the Company to maintain, as of the end of each fiscal quarter, a maximum consolidated leverage ratio of 3.5 to 1.0 (which shall be temporarily increased (a) to 4.0 to 1.0 upon the consummation of the Merger and (b) upon notice by the Company to JPMorgan as a result of other material acquisitions from time to time, subject to customary limitations, and provided that the maximum permitted consolidated leverage ratio shall not exceed 4.0 to 1.0).

Following the Company’s entry into the Credit Agreement, JPMorgan’s commitment to provide a 364-day senior unsecured bridge loan facility in an aggregate principal amount of up to $1.5 billion (as more particularly described in the Company’s Current Report on Form 8-K dated July 31, 2023) has been terminated and canceled.

A copy of the Credit Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The foregoing description of the Credit Agreement is a summary only and is qualified in its entirety by the terms of the Credit Agreement.

On August 28, 2023 Palleon Pharmaceuticals, a clinical-stage company pioneering glyco-immunology drug development to treat cancer and inflammatory diseases, reported that Fierce Biotech has recognized the company as one of its "Fierce 15" for 2023 (Press release, Palleon Pharmaceuticals, AUG 28, 2023, View Source [SID1234634733]). This annual report features the most innovative and promising biotechnology companies in the industry.

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"It is an honor to be named to the Fierce 15 and to be recognized for our work pioneering the transformational field of glyco-immunology," said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "As we continue to advance our therapies in the clinic, this recognition provides validation of the strength of our team, our technologies, and our strategy to bring much-needed new therapeutic options to patients across multiple disease areas."

Palleon was co-founded by Dr. Carolyn Bertozzi, recipient of the 2022 Nobel Prize in Chemistry for the invention of bioorthogonal chemistry, a technology which enabled the company’s foundational science. In April 2023, Palleon announced Phase 1 results from the GLIMMER-01 trial to evaluate its lead candidate in oncology, E-602 as a monotherapy, demonstrating proof of mechanism, including dose dependent desialylation and dose dependent immune system activation. Additionally, E-602 was found to be well tolerated across the entire dose range evaluated with no dose limiting toxicities.

For the past 21 years, the Fierce Life Sciences team has assessed hundreds of companies for inclusion in the ‘Fierce 15’ special report. To curate this list, Fierce considers a diverse range of factors, including the robustness of technology, partnerships, venture support, and competitive positioning within the market. This special report celebrates innovation and creativity in the face of intense competition.

On August 28, 2023 Novocure (NASDAQ: NVCR) reported that the phase 3 ENGOT-ov50 / GOG-3029 / INNOVATE-3 clinical trial of Tumor Treating Fields (TTFields) together with paclitaxel in patients with platinum-resistant ovarian cancer did not meet its primary endpoint of overall survival (OS) at the final analysis (Press release, NovoCure, AUG 28, 2023, View Source [SID1234634732]). Patients randomized to receive TTFields therapy plus paclitaxel (n=280) demonstrated a median OS of 12.2 months versus a median OS of 11.9 months in patients treated with paclitaxel alone (n=278) (HR: 1.008). Consistent with previously reported studies, TTFields therapy was well-tolerated with no added systemic toxicities.

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"While the final results of the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial differ from our initial expectation, these data add important context to the treatment paradigm"

"Recurrent ovarian cancer is a particularly aggressive cancer and options for patients diagnosed with platinum-resistance remain extremely limited," said Ignace Vergote, MD, PhD, Principal Investigator and Chairman of the Belgium and Luxembourg Gynaecological Oncology Group and Professor at the Catholic University of Leuven, Belgium. "We are committed to continuing research with TTFields and exploring innovative approaches to treat this area of immense unmet need, and we are extremely grateful to all the investigators and patients for their participation in these studies."

The ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial enrolled patients with a maximum of five total prior lines of systemic therapy. An analysis of exploratory subgroups suggests a potential survival benefit in patients who received only one prior line of therapy. This signal could merit further exploration given the unmet need for the ~20% of ovarian cancer patients who have a limited response to frontline platinum-based treatment. Full evaluation of the data from the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial, including subgroup analyses, is ongoing.

"While the final results of the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial differ from our initial expectation, these data add important context to the treatment paradigm," said David O’Malley, MD, Professor of Obstetrics and Gynecology at The Ohio State University Wexner College of Medicine and Director of the Division of Gynecologic Oncology at The James Comprehensive Cancer Center. "We see treatment exposure and number of prior therapies are relevant and can drive outcomes, and we will leverage these data as we explore and identify new opportunities to treat this deadly disease."

"The INNOVATE-3 clinical trial set out to harness the unique mechanisms of Tumor Treating Fields to extend survival in platinum-resistant ovarian cancer," said William Doyle, Novocure’s Executive Chairman. "While today’s update is disappointing, we are encouraged by the signal identified from the exploratory analysis which suggests the potential for a clinical benefit when TTFields therapy is initiated early in a patient’s treatment journey. We are deeply grateful to the patients who participated in this clinical trial, their loved ones, and to the trial investigators."

Novocure will work with investigators to share the full results with the scientific community.

About ENGOT-ov50 / GOG-3029 / INNOVATE-3
The ENGOT-ov50 / GOG-3029 / INNOVATE-3 clinical trial was designed to evaluate the safety and effectiveness of TTFields together with paclitaxel in patients with platinum-resistant ovarian cancer. The primary endpoint of INNOVATE-3 was overall survival. Secondary endpoints include progression-free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. Enrollment in the trial closed in October 2021 with 540 patients enrolled, beginning the minimum 18-month follow-up period.

The European Network for Gynaecological Oncological Trial groups ("ENGOT") and The GOG Foundation, Inc. ("GOG"), third-party clinical trial networks, collaborated with Novocure on the trial. Both ENGOT and GOG were involved in the development and facilitation of the trial at leading cancer centers in Europe and the United States.

About Ovarian Cancer
In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old.

Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease. Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy. Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases. Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence. Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor.

About Tumor Treating Fields Therapy
Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.