On November 14, 2023, Xencor reported that it has entered into an Amended and Restated Collaboration and License Agreement (the "New Collaboration Agreement") with Genentech, Inc., a Delaware corporation, having its principal place of business at 1 DNA Way, South San Francisco, California 94080 ("GNE"), and F. Hoffmann-La Roche Ltd, a corporation organized and existing under the laws of Switzerland, having its principal place of business at Grenzacherstrasse 124, CH 4070 Basel, Switzerland ("Roche") (GNE and Roche, collectively, "Genentech") (Filing, 8-K, Xencor, NOV 15, 2023, View Source [SID1234637709]). The New Collaboration Agreement is effective as of June 1, 2024 (the "Effective Date") and, as of that date, will replace the current Collaboration and License Agreement between the Company and Roche which was entered into on February 4, 2019 (the "Original Collaboration Agreement"). The Original Collaboration Agreement will remain effective for the period between February 4, 2019 and the Effective Date.

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The Company has exercised its option under the Original Collaboration Agreement to convert its current development cost and profit-sharing arrangement with Genentech into a royalty and milestone payment financial arrangement (the "Royalty Conversion"). Pursuant to the terms of the New Collaboration Agreement, the Company and Genentech have agreed on the financial and other terms to implement the Royalty Conversion. Pursuant to the Royalty Conversion, in connection with any program under the Original Collaboration Agreement, including XmAb306 (RO7310729), the Company will be entitled to receive tiered royalties on a product-by-product and country-by-country basis ranging from low double-digit to mid-teens percentages. The Company will also be entitled to receive up to $600 million in milestones, including $115 million in development milestones, $185 in regulatory milestones and $300 million in sale-based milestones.

Pursuant to the terms of the New Collaboration Agreement, after the Effective Date, Genentech will assume sole responsibility over all clinical, regulatory, and commercial activities.

The descriptions of the contractual arrangements contained herein do not purport to be complete and are qualified in their entirety by reference to the copy of the actual agreement which will be filed as exhibits to the Company’s Annual Report on Form 10-K for the period ending December 31, 2023.

On November 15, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and provided comprehensive preclinical data for both RP-1664 and the Company’s Polq inhibitor, RP-3467 (Press release, Repare Therapeutics, NOV 15, 2023, View Source [SID1234637708]).

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RP-1664 is a potential first-in-class, selective, oral PLK4 inhibitor that is synthetic lethal with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for survival in the presence of high levels of TRIM37. Preclinical studies demonstrate RP-1664 drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in nearly all high-grade neuroblastomas.

RP-3467 is a potential best-in-class inhibitor of DNA polymerase theta, or Polq. Polq is a synthetic lethal target associated with homologous recombination deficiency (HRD) tumors, including those with BRCA1/2 mutations or other genomic alterations. Data suggest that RP-3467 works synergistically with therapies that result in double stranded DNA breaks, such as PARP inhibition, radioligand therapy and multiple chemotherapies and antibody-drug conjugates (ADCs). Additionally, initial data suggest that Polq inhibition may interfere with mechanisms central to the development of PARPi resistance.

"We are excited to announce the initial clinical approach for RP-1664 based on highly compelling preclinical data supporting its potential for treating TRIM37-high tumors," said Lloyd M. Segal, President and CEO of Repare. "We are also pleased to share preclinical data from our RP-3467 program supporting its significant potential across multiple high-value therapeutic opportunities. These programs represent our third and fourth internally developed clinical candidates and provide further confirmation of Repare’s powerful discovery platform. We look forward to advancing both RP-1664 and RP-3467 into Phase 1 clinical trials in 2024."

RP-1664 Highlights

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RP-1664 is a highly potent, selective and bioavailable PLK4 inhibitor that is synthetic lethal with TRIM37 gain of function.

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RP-1664 demonstrated robust and dose-dependent monotherapy activity in multiple TRIM37-high preclinical models across a variety of tumor types, including breast cancer, non-small cell lung cancer (NSCLC) and neuroblastoma.

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The Company plans to initiate a Phase 1 dose escalation study of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024.

RP-3467 Data Highlights

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RP-3467 is a highly potent and selective inhibitor of the Polq helicase domain.

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RP-3467 demonstrates synergy with PARP inhibitor activity, resulting in durable, complete tumor regressions in multiple preclinical models.

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Preclinical studies also show combination potential with multiple other modalities, including RLT, chemotherapy and ADCs.

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The Company plans to initiate a Phase 1 dosing finding clinical trial of RP-3467 in the second half of 2024.

"Preclinical data for RP-1664 demonstrate early and promising activity in TRIM37-high tumors, including breast cancer, NSCLC and neuroblastoma," said Michael Zinda, Ph.D., EVP, Chief Scientific Officer of Repare. "The durable, complete regressions observed in the preclinical RP-3467 and PARPi combination studies are also extremely exciting and demonstrate the broad combination potential of our potent and selective Polq helicase inhibitor. Repare plans to investigate RP-3467 with a focus on its potential as a combination partner across agents that induce double stranded DNA breaks, including RLT, ADCs, and a range of chemotherapies."

Conference Call and Webcast

Repare will host a conference call and webcast today, November 15, 2023, at 8:00 a.m. ET. To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

On November 15, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, NOV 15, 2023, View Source [SID1234637707]):

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Piper Sandler 35th Annual Healthcare Conference at 8:30 a.m. ET on Tuesday, November 28, 2023

The session may be accessed from the "Investors & Media" page of Regeneron’s website at View Source A replay and transcript of the webcast will be archived on the Company’s website for at least 30 days.

On November 15, 2023 Orionis Biosciences, a life sciences company pioneering the creation of highly selective and tunable therapeutics for cancer and other diseases, reported that the first patient has been dosed in a Phase 1 clinical trial of ORB-011, an attenuated, cis-targeted interferon immunotherapy based on the company’s A-Kine platform (Press release, Orionis Biosciences, NOV 15, 2023, View Source [SID1234637706]). ORB-011 is the first clinical candidate to emerge from the platform, which engineers cytokines to be highly selective for specific cellular targets while avoiding the broad systemic activity and associated toxicities observed with traditional cytokine therapies. The company is also announcing the appointment of Tony Fadell to its Board of Directors.

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ORB-011 is a first-in-class modified interferon designed to act with a high level of precision on cDC1 dendritic immune cells, potent activators of tumor cell killing CD8+ T cells. Preclinical research has shown that selective activation of cDC1s with such conditionally active interferon molecules translates into effective antitumor activity. Targeted activation of cDC1 was also well tolerated in non-human primate studies.

"The beginning of this clinical study represents a major milestone for Orionis and our A-Kine protein engineering platform, which combines a range of redesigned immune-modulatory cytokines with targeting modules aimed at cell types of therapeutic relevance. ORB-011 has the potential to harness the therapeutic activity of interferon in a new way," said Nikolai Kley, Ph.D., Founder, President, and Chief Executive Officer of Orionis Biosciences. "Interferons and other cytokines in our pipeline are powerful immune-activating agents. By localizing their activity to specific target cells, and exploiting communication networks across immune cells, we are evolving immunotherapies with unique translational potential."

Tony Fadell, Principal at Build Collective has joined the Orionis Board of Directors. He is the founder and former CEO of Nest, the company that pioneered the "Internet of Things." Tony was the SVP of Apple’s iPod Division and led the team that created the first 18 generations of the iPod and the first three generations of the iPhone. Tony holds more than 300 patents and is the author of the New York Times Best-Seller "BUILD – An Unorthodox Guide to Making Things Worth Making."

"Tony is a tremendously supportive and collaborative investor, bringing a broad range of expertise and insights to countless topics important to the strategic growth and vision of our business," said Dr. Kley. "His increased involvement will help us take Orionis to the next level and execute on our mission to bring new breakthrough medicines to patients in need."

"Orionis deploys the most powerful new foundational technologies available: Robotics plus Assay-on-Chip for high-throughput screening, generative AI for structure-based drug design…to name only a few," said Fadell. "This is what’s needed to combat the toughest, currently undruggable diseases. I’m excited about Orionis’s focus on immunotherapies: activating and directing our natural immune system to go after cancer. I can’t think of a more worthwhile endeavor."

About ORB-011
ORB-011 is a clinical-stage, targeted interferon that is designed to specifically activate cDC1 dendritic cells, immune cells that are specialized in presenting tumor antigens to, and activating, tumor cytotoxic CD8 T cells. It achieves localized activity by a unique mechanism of induced proximity on the cell surface of cDC1s. Orionis is evaluating ORB-011 in a Phase 1 open-label dose-escalation study (NCT05947474) for patients with recurrent or refractory solid tumors amenable to medically safe serial biopsies, including, but not limited to, colorectal cancer, HR+ or triple-negative breast cancer, non-small cell lung cancer, pancreatic cancer, head and neck squamous cell carcinoma, metastatic melanoma, bladder/urothelial, gastric cancers, esophageal, renal cell, hepatic and ovarian cancers. The Phase 1 clinical trial will provide initial safety, pharmacokinetic and pharmacodynamic readouts, and identify a dose of ORB-011 for use in future studies. It is being conducted at this time at the M.D. Anderson Cancer Center in Houston, Texas and at Honor Health Research Institute in Scottsdale, Arizona.

About the A-Kine Platform
Orionis’s A-Kine platform is designed to harness the intrinsic function and therapeutic potential of cytokines as key immune system regulators and natural defenders against cancer and infections. A-Kines are designed to be highly selective for intended cell targets, such as immune cells, and to avoid broad systemic activity and associated toxicities observed with traditional cytokine therapies. The platform covers multiple cytokine classes, including interferons, interleukins, and tumor necrosis factors, to generate a diversified pipeline of targeted immunotherapy candidates. These redesigned cytokines are leveraged to restart a stalled Cancer Immunity Cycle at multiple different positions to elicit natural mechanisms of immune attack against a variety of cancers.

On November 15, 2023 Immunome presented its corporate presentation (Presentation, Immunome, NOV 15, 2023, View Source [SID1234637705]).

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