Repare Therapeutics to Participate at the H.C. Wainwright 2nd Annual Precision Oncology Conference

On October 18, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported that members of its senior management team will participate in a fireside chat at the H.C. Wainwright 2nd Annual Precision Oncology Conference on Wednesday, October 20, 2021 at 12:30 p.m. Eastern Time (Press release, Repare Therapeutics, OCT 18, 2021, View Source [SID1234591463]).

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A live webcast of the fireside chat can be accessed in the Investor section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days.

Xilio Therapeutics Announces FDA Clearance of Investigational New Drug Application for XTX202 for the Treatment of Solid Tumors

On October 18, 2021 Xilio Therapeutics, Inc. (Xilio) a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to evaluate XTX202, its tumor-selective IL-2 product candidate, as a potential treatment for patients with solid tumors (Press release, Xilio Therapeutics, OCT 18, 2021, View Source [SID1234591462]). XTX202 is designed to localize activity in the tumor microenvironment (TME), with the goal of overcoming the known tolerability challenges of existing IL-2 therapies while achieving enhanced anti-tumor activity.

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"We are excited to have received FDA clearance for our IND application for XTX202," said Martin Huber, M.D., president of research and development and chief medical officer of Xilio. "IL-2 has shown potential for long-term, durable complete responses in certain cancers, but life-threatening toxicity has limited its use to a small subset of patients. We have designed XTX202 with the goal of delivering enhanced anti-tumor activity while minimizing the known liabilities of existing IL-2 therapies. We look forward to beginning Phase 1/2 development to evaluate the potential that XTX202 may offer as both a monotherapy and combination agent for patients in need."

Leveraging its proprietary geographically precise solutions (GPS) platform, Xilio designed XTX202 to be activated selectively in the TME, resulting in localized clinical activity without dose-limiting toxicities. In preclinical studies, XTX202 exhibited tumor-selective biological activity and anti-tumor activity comparable to aldesleukin, a high-dose IL-2 therapy, at its maximum tolerated dose, while minimizing the severe toxicity observed with aldesleukin. XTX202 was well-tolerated in non-human primate models up to 10 mg/kg weekly.

Xilio expects to initiate a Phase 1/2 dose-escalation monotherapy trial for XTX202 in patients with solid tumors who have previously received an anti-PD(L)1 treatment regimen in the first quarter of 2022.

ITM and CNL Sign Memorandum of Understanding to Pursue Global Development and Production of Rare Medical Radioisotope, Actinium-225

On October 18, 2021 ITM Isotope Technologies Munich SE, a leading radiopharmaceutical biotech company, and Canadian Nuclear Laboratories (CNL), Canada’s premier nuclear science and technology organization, reported that the companies have signed a Memorandum of Understanding (MoU) to explore the development and industrial-scale production of Actinium-225, an extremely rare alpha-emitting radioisotope with heightened potential in precision oncology (Press release, ITM Isotopen Technologien Munchen, OCT 18, 2021, View Source [SID1234591461]). Under the terms of the agreement, the organizations will collaborate on the development, manufacturing, and distribution pathways for the medical radioisotope. Further details of the agreement have not been disclosed.

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Targeted Alpha Therapy (TAT) has been rapidly gaining growing interest from the scientific and medical community. Alpha-emitters, particularly Actinium-225, are in high demand for their ability to cause irreparable damage to cancer cells. Notably, Actinium-225 emits powerful, high-energy alpha particles with a short penetration range, which enables highly precise treatment of tumor cells, including hard-to-target micro metastases, with minimal impact to surrounding healthy tissue. In preclinical studies, TAT has shown remarkable results, destroying cancer cells by effectively breaking the bonds in their DNA. Actinium-225 can be labelled to a variety of peptide ligands or antibodies to specifically target cancer cells in a wide range of tumor indications.

As the current annual global production of Actinium-225 is miniscule, one of the biggest challenges in harnessing the full potential of the alpha-emitter is ensuring its supply. CNL and ITM have the expertise and infrastructure in place to work to sufficiently bypass the supply hurdle to develop and produce this coveted radioisotope with huge therapeutic potential.

"CNL is very excited to enter into this agreement with ITM, an industry leader that shares our ambition of bringing the next-generation of medical radioisotopes to the global market," commented Joe McBrearty, CNL’s President and CEO. "It is also an exciting evolution of CNL’s work in the field of medical radioisotopes, and makes use of our capabilities in target development, radiochemistry, radioisotope analysis and by-product management. Working with ITM, we hope to leverage these capabilities to accelerate the development of this promising new isotope, and to establish a commercial pipeline for what we believe will be a ground-breaking new cancer treatment."

"It is always a pleasure to work alongside another radiotherapeutic industry leader like CNL in the development of a radioisotope with the potential to address a high unmet need. We look forward to sharing our expertise in the global production and supply of the highest quality radioisotopes in our shared mission of exploring the otherwise untapped potential of Actinium-225, commonly referred to as the ‘rarest drug on earth’. We are eager to unveil the therapeutic value of this radioisotope which we believe has the potential to unlock revolutionary TAT treatments," said Steffen Schuster, CEO of ITM.

ITM is a world leader in the development, production and global supply of radiotherapeutics and diagnostics, and maintains an evolving precision oncology pipeline. Coupled with CNL’s extensive scientific infrastructure and vast experience in developing and distributing medical radioisotopes, the companies are very well-positioned to produce and provide this highly sought-after radioisotope to the global industry.

Under the terms of the agreement, CNL will be responsible for the research and development as well as the production of Actinium-225. The company is already developing and producing Actinium-225 in research-scale quantities using Thorium-229 generators. ITM will be responsible for further processing Actinium-225 to Good Manufacturing Practices (GMP) standard and will subsequently have the primary responsibility for associated regulatory processes, marketing and sales of the product. CNL and ITM aim to leverage their capabilities towards establishing a continuous commercial supply of GMP-grade Actinium-225 for the global market. Both parties are working towards signing a more formal agreement in the form of a Collaborative Venture.

Entry into a Material Definitive Agreement

On October 18, 2021, Thermo Fisher Scientific (Finance I) B.V. ("Thermo Fisher International"), an indirect, wholly-owned finance subsidiary of Thermo Fisher Scientific Inc. (the "Company"), reported that issued €1,750,000,000 aggregate principal amount of 0.800% Senior Notes due 2030 (the "2030 Notes"), €1,500,000,000 aggregate principal amount of 1.125% Senior Notes due 2033 (the "2033 Notes"), €1,250,000,000 aggregate principal amount of 1.625% Senior Notes due 2041 (the "2041 Notes") and €750,000,000 aggregate principal amount of 2.000% Senior Notes due 2051 (the "2051 Notes", and, together with the 2030 Notes, the 2033 Notes and the 2041 Notes, the "Notes") in a public offering (the "Offering") pursuant to a registration statement on Form S-3 (File No. 333-229951) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Notes, each as previously filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, Thermo Fisher Scientific, OCT 18, 2021, View Source [SID1234591460]). The Company has fully and unconditionally guaranteed the Notes on a senior unsecured basis (the "Guarantee" and, together with the Notes, the "Securities").

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The Securities were issued under an indenture, dated as of August 9, 2016 (the "Base Indenture"), and the Third Supplemental Indenture, dated as of October 18, 2021 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), among Thermo Fisher International, as issuer, the Company, as guarantor, and The Bank of New York Mellon Trust Company, N.A., as trustee.

Prior to July 18, 2030, in the case of the 2030 Notes, July 18, 2033, in the case of the 2033 Notes, April 18, 2041, in the case of the 2041 Notes and April 18, 2051, in the case of the 2051 Notes (each such date, a "Par Call Date"), Thermo Fisher International may redeem the Notes of any such series, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the Notes to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such Notes to be redeemed matured on their applicable Par Call Date), discounted to the date of redemption on an annual basis (ACTUAL/ACTUAL (ICMA)), using a discount rate equal to the Comparable Bond Rate (as defined in the Indenture) plus 20 basis points, in the case of the 2030 Notes, 20 basis points, in the case of the 2033 Notes, 25 basis points, in the case of the 2041 Notes and 30 basis points, in the case of the 2051 Notes, plus in each case, accrued and unpaid interest on the Notes being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the applicable Par Call Date, the Company may redeem the Notes of any series, in whole at any time or in part from time to time, at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the date of redemption.

Upon the occurrence of a change of control (as defined in the Indenture) of the Company and a contemporaneous downgrade of the Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings Limited, Thermo Fisher International will, in certain circumstances, be required to make an offer to purchase the Notes at a price equal to 101% of the principal amount of the Notes, plus accrued and unpaid interest, if any, to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of Thermo Fisher International. The Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of Thermo Fisher International and rank senior in right of payment to any existing and future indebtedness of Thermo Fisher International that is subordinated to the Notes. The Notes are also effectively subordinated to any existing and future secured indebtedness of Thermo Fisher International to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries.

The Guarantee is a general unsecured obligation of the Company. The Guarantee ranks equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and will rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Guarantee. The Guarantee is also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and is structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries (other than, with respect to Thermo Fisher International, the Notes).

The Indenture contains limited affirmative and negative covenants of the Company and Thermo Fisher International. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The Indenture also limits the ability of each of the Company and Thermo Fisher International to merge or consolidate or sell all or substantially all of their respective assets.

Upon the occurrence of an event of default under the Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of Thermo Fisher International under the Notes may be accelerated, in which case the entire principal amount of the Notes would be immediately due and payable.

Wilmer Cutler Pickering Hale and Dorr LLP, U.S. counsel to the Company and Thermo Fisher International, has issued an opinion to the Company and Thermo Fisher International, dated October 18, 2021, regarding the legality of the Securities, and Linklaters LLP, Dutch counsel to Thermo Fisher International, has issued an opinion to Thermo Fisher International, dated October 18, 2021, regarding the Notes. Copies of these opinions are filed as Exhibits 5.1 and 5.2 hereto, respectively.

The foregoing description of certain of the terms of the Indenture does not purport to be complete and is qualified in its entirety by reference to the full text of each of the Base Indenture and the Supplemental Indenture, which are filed with this report as Exhibits 4.1 and 4.2 hereto, respectively. Each of the foregoing documents is incorporated herein by reference.

Sirnaomics to Present STP705, the Company’s Lead Drug Candidate, for the Treatment of Cutaneous Squamous Cell Carcinoma in situ, at the 2021 Fall Clinical Dermatology Conference

On October 18, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported that Professor Brian Berman, M.D., Ph.D., Professor Emeritus, Dermatology and Dermatologic Surgery, University of Miami will be giving a talk on the clinical study result of the Company’s lead drug candidate, STP705, at the 2021 Fall Clinical Dermatology Conference, as the principal investigator (Press release, Sirnaomics, OCT 18, 2021, View Source [SID1234591459]). The Company will also exhibit a poster at the conference highlighting results from a Phase IIa clinical trial of STP705 for the treatment of cutaneous squamous cell carcinoma in situ (nonmelanoma skin cancer). The hybrid conference is taking place in person at the Wynn Las Vegas hotel in Las Vegas, NV, USA from October 21-24, 2021.

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Talk: New and Future Innovations in Dermatologic Care
Title: Advances in Therapeutic Technology: STP705 siRNA for in situ Squamous Cell Carcinoma
Presenter: Brian Berman, M.D., Ph.D., Professor Emeritus, Dermatology and Dermatologic Surgery, University of Miami; Co-Director Center for Clinical and Cosmetic Research, Aventura, FL, USA
Overview: Clinical trial results showing STP705, used to target TGF-β1 and COX-2 siRNAs for the treatment of nonmelanoma skin cancer, has demonstrated rates of histological clearance that rival surgical excision combined with improved cosmetic appearance.
Date and Time: October 21, 2021, from 10:20 AM to 10:55 AM PT
Location: Wynn Las Vegas,Cristal 2, 4, 6
Poster:

Title: Open Label, Phase I/II, Dose Escalation Study to Evaluate Safety and Efficacy of Intralesional Injection of a TGF-β1/COX-2 dual targeting small interfering (si)RNA therapeutic, in Adult Patients with Cutaneous Squamous Cell Carcinoma in situ (isSCC)
Date and Time: October 21, 2021, from 7:00 AM to 4:30 PM PT; October 22, 2021, from 7:00 AM to 12:30 PM PT
Location: Wynn Las Vegas,Cristal 1, 3, 5