On December 21, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported the closing of Gilead’s option exercises to three programs in Arcus’ clinical-stage portfolio and a new research collaboration between the two companies. On November 17, 2021, Gilead exercised its options to anti-TIGIT molecules domvanalimab and AB308, as well as clinical candidates etrumadenant (dual adenosine A2a/A2b receptor antagonist) and quemliclustat (small molecule CD73 inhibitor) (Press release, Gilead Sciences, DEC 21, 2021, View Source [SID1234597555]).

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The closing occurred following the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

Under the terms of the parties’ Option, License and Collaboration Agreement, as amended in connection with Gilead’s three option exercises (the "2020 Agreement"), the closing of this transaction triggers option payments totaling $725 million from Gilead to Arcus, expected to be paid in early Q1 2022. With closing of the transaction for all three programs, the $100 million option continuation payment previously due in Q3 2022 will not be made by Gilead. In addition, the parties will co-develop and share the global costs related to these clinical programs. If the optioned molecules achieve regulatory approval, Gilead and Arcus will co-commercialize and equally share profits in the U.S. Outside of the U.S., Gilead holds exclusive commercialization rights, subject to any rights of Arcus’s existing collaboration partners, and Gilead would pay Arcus tiered royalties on net sales of each optioned product.

About the Collaboration

In May 2020, Gilead and Arcus entered into a 10-year collaboration that provided Gilead immediate rights to zimberelimab and the right to opt into all other Arcus programs arising during the collaboration term. In November 2021, Gilead and Arcus amended the collaboration in connection with Gilead’s option exercise for three of Arcus’s clinical stage programs. For all other programs that are in clinical development or new programs that enter clinical development thereafter, the opt-in payments are $150 million per program. Gilead’s option, on a program-by-program basis, expires after a specified period of time following the achievement of a development milestone for such program and Arcus’s delivery to Gilead of the requisite qualifying data package. Concurrent with the May 2020 collaboration agreement, Gilead and Arcus entered into a stock purchase agreement under which Gilead made a $200 million equity investment in Arcus. That stock purchase agreement was amended and restated in February 2021 in connection with Gilead’s increased equity stake in Arcus from 13% to 19.7%, with an additional $220 million investment.

Upon closing of Gilead’s exercise of its option to a program, the two companies will co-develop and share global development costs for the joint development program, subject to certain opt-out rights of Arcus in some cases and expense caps on its spending and related subsequent adjustments. For each optioned program, provided that Arcus has not exercised its opt-out rights, if any, Arcus has an option to co-promote in the U.S. with equal profit share. Gilead has the right to exclusively commercialize any optioned programs outside of the U.S., subject to the rights of Arcus’s existing collaboration partners to any territories, and, for clinical stage programs that Gilead has opted into, Gilead will pay Arcus tiered royalties as a percentage of net sales ranging from the mid or high teens to the low twenties.

Zimberelimab, domvanalimab, AB308, etrumadenant and quemliclustat are investigational agents and have not been proven safe and efficacious.

On December 21, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its executives will be speaking at the following investor conference (Press release, Gilead Sciences, DEC 21, 2021, View Source [SID1234597554]):

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J.P. Morgan Healthcare Conference and Q&A Breakout on Monday, January 10 beginning at 11:15 a.m. Eastern Time

The live webcast can be accessed at the company’s investors page at investors.gilead.com. The replay will be available for at least 30 days following the presentation.

On December 21, 2021 CytRx Corporation (OTCQB:CYTR) ("CytRx" or the "Company"), a specialized biopharmaceutical company focused on research and development in oncology and neurodegenerative diseases, highlighted ImmunityBio, Inc.’s (NASDAQ: IBRX) ("ImmunityBio") reported that recent clinical developments in the study of aldoxorubicin to treat various cancers (Press release, CytRx, DEC 21, 2021, View Source [SID1234597551]).

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CytRx out-licensed global development, manufacturing and commercialization rights for aldoxorubicin to ImmunityBio in 2017. The Company has an agreement with ImmunityBio that can yield up to $343 million in potential milestone payments as well as prospective royalties on sales of aldoxorubicin.

Pancreatic Cancer

ImmunityBio’s QUILT 88 study is a randomized, three-cohort, open-label study that evaluates the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with PD-L1 t-haNK, Anktiva (N-803), and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer.

On October 13, ImmunityBio announced that the third cohort ("Cohort C") in the QUILT 88 study, which includes patients with third-line or greater disease, is fully enrolled and of the evaluable patients, 90% (43/48) have exceeded the historical survival rates of approximately two months with standard-of-care chemotherapy. Based on the strength of this early data and the significant unmet medical need, ImmunityBio submitted an amendment to the U.S. Food and Drug Administration to increase enrollment in Cohort C, and enrollment is actively ongoing.

The interim results of Cohort C in the QUILT 88 study have been selected for presentation at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2022 and the data to date continues to show that the historical overall survival in patients who have enrolled with 3rd, 4th, 5th and even 6th line metastatic pancreatic cancer exceeds any historical overall survival rate for this advanced stage of disease, for which there are no further treatment options available.

Triple Negative Breast Cancer and Head and Neck Cancer

ImmunityBio continues to study the effectiveness of N-803 and aldoxorubicin in combination with PD-L1 t-haNK in Phase 1 / 2 clinical trials to treat triple negative breast cancer and head and neck cancer.

Glioblastoma

A Phase 1 / 2 trial has been submitted for the study of N-803 and aldoxorubicin in Glioblastoma. Further updates will be provided in 2022.

On December 21, 2021 Precision Molecular, Inc. (PMI), a clinical-stage company developing targeted radiopharmaceuticals and theranostics for patients with cancer, reported it has executed a licensing agreement with Johns Hopkins University for exclusive rights to an astatine-211-labeled inhibitor of prostate-specific membrane antigen (PSMA) which is typically elevated in prostate cancer cells (Press release, Precision Molecular, DEC 21, 2021, View Source [SID1234597549]). PMI is developing this astatine-211-labeled inhibitor of PSMA as PMI21 and expects to initiate clinical trials in the first half of next year. Martin Pomper, M.D., Ph.D., director of nuclear medicine and molecular imaging at Johns Hopkins and Michael Zalutsky, Ph.D., professor of radiology, at the Duke University School of Medicine are co-inventors of the astatine-211-labeled targeted alpha therapy.

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Radiopharmaceuticals consist of a radionuclide and a targeting molecule that delivers a sufficient level of radiation to disease sites. Radionuclides used for oncology applications must emit radiation with a relatively short path length to maximize impact on cancer cells while minimizing effects on healthy tissue; two main types of radiation used in targeted radionuclide therapy are alpha particles and beta particles.

"When designing radiopharmaceuticals, the choice of radionuclide has important implications related to efficacy and toxicity," said Dr. Zalutsky, senior advisor to PMI. "Astatine-211 emits a single alpha particle which has more energy and travels a shorter distance than other forms of radiation, offering the potential to kill cancer cells while limiting damage to surrounding tissue. In contrast, beta particles emitted by other radionuclides can travel further which increases the risk of irradiating normal tissue. Astatine-211 also offers an advantage over other alpha emitters such as actinium-225 which emits four alpha particles. These particles can break the bonds that hold the radionuclide to its targeting molecule, releasing the radioactivity and potentially causing off-target toxicity."

PMI21 is designed to target PSMA which is present at a low level in normal prostate tissue, but markedly elevated in prostate cancer cells. The vast majority of PSMA exists on the surface of prostate cells making it highly accessible for both diagnostic imaging and drug delivery.

"The PSMA-binding and astatine labeling functions of PMI21 have been optimized in combination," said Seulki Lee, Ph.D., Chief Executive Officer of PMI. "It has been engineered for high tumor uptake and rapid clearance from normal tissues to minimize toxicity which has been a challenge with some other PSMA-targeted radiotherapies. We believe this compound has the potential to offer major advantages to what is currently in development, and we look forward to advancing PMI21 into clinical trials."

On December 21, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to discover and develop novel therapeutics, reported the first patient has been dosed in the Company’s Phase 1 clinical trial of RP-6306, a first-in-class small molecule candidate targeting PKMYT1, in combination with gemcitabine for the treatment of molecularly selected advanced solid tumors (NCT05147272) (the "MAGNETIC" trial) (Press release, Repare Therapeutics, DEC 21, 2021, View Source [SID1234597548]).

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"Dosing of the first patient in the Phase 1 RP-6306 trial in combination with gemcitabine, alongside our ongoing monotherapy "MYSTIC" trial, is an exciting milestone for Repare as we continue to advance our unique precision oncology pipeline across multiple fronts," said Maria Koehler MD, PhD, Chief Medical Officer of Repare. "MAGNETIC will assess the safety and tolerability of RP-6306 in combination with gemcitabine. It will enroll approximately 104 patients with tumors harboring genomic alterations that were identified through Repare’s proprietary STEP2 screens. We look forward to providing updates on RP-6306 later in 2022."

This multicenter Phase 1 study aims to determine the maximum tolerated dose (MTD), identify a recommended phase 2 dose (RP2D) and preferred schedule, and assess preliminary anti-tumor activity.

About RP-6306

RP-6306 is a first-in-class, selective, orally available inhibitor of PKMYT1 that was discovered and developed entirely in-house by Repare. Through Repare’s SNIPRx screen campaign for targets that are SL with CCNE1 amplification, the Company identified and validated this novel SL gene that has the characteristics of a therapeutic target. Repare has developed novel and selective inhibitors against PKMYT1, which demonstrated compelling pre-clinical anti-tumor activity alone and in combination with certain anticancer agents, and subsequently announced the advancement of a clinical candidate to this potential, first-in-class program.