Corporate presentation

On January 8, 2024 Nkarta presented its corporate presentation (Presentation, Nkarta, JAN 8, 2024, View Source [SID1234639093]).

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Iktos and Nerviano Medical Sciences S.r.l Announce Collaboration in Artificial Intelligence for New Drug Discovery

On January 8, 2024 Iktos, a company specialized in Artificial Intelligence for new drug design, and Nerviano Medical Sciences S.r.l (NMS), a leading Italian clinical stage biotech discovering and developing innovative therapies for the treatment of cancer, reported a collaboration agreement in AI for unprecedented kinase project (Press release, Nerviano Medical Sciences, JAN 8, 2024, View Source [SID1234639092]). As per the agreement, NMS will leverage Iktos’s expertise in drug design services, with the ultimate goal of identifying at least one promising candidate molecule. Iktos’s innovative generative modeling technology platform, Makya, will be employed to apply a ligand- and structure-based approach in designing novel molecules that align with NMS’s candidate drug target profile (CDTP); Iktos’s generative AI approach uniquely enables the exploration of chemical space and produces innovative molecule designs with greater freedom to operate and good synthetic tractability thanks to integration with Iktos’s retrosynthesis AI technology platform Spaya.

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"We are excited about the prospect of collaborating with IKTOS, a proven leader in AI-powered drug discovery platforms to delivery one candidate drug for a truly, unprecedented novel kinase" said Hugues Dolgos, Pharm.D., Chief Executive Officer of NMS.

"We are excited and proud to collaborate with Nerviano Medical Sciences S.r.l, a leading company focused on the discovery and development of oncology drugs and the largest oncological R&D company in Italy. In the framework of our collaboration, the NMS team will use Makya, Iktos proprietary Gen AI software in their discovery of a novel candidate drug" said Dr. Quentin Perron, Co-founder and CSO of Iktos. "Indeed, at Iktos, we are committed to developing innovative technologies that enhance the chance of success of small molecule discovery. Our mission is to expedite drug discovery through the application of AI, which we achieve by integrating our robust algorithmic technology, leveraging our expertise from numerous successful collaborations."

Mural Oncology Announces Enhancements to Late-Stage Clinical Trials

On January 8, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported strategic changes to its ARTISTRY-6 and ARTISTRY-7 clinical trials designed to generate more meaningful clinical data for these late-stage, potentially registrational trials of nemvaleukin (Press release, Mural Oncology, JAN 8, 2024, View Source [SID1234639091]).

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These changes are as follows:

Cohort 2 of ARTISTRY-6 is a potentially registrational, phase 2 trial evaluating nemvaleukin as a monotherapy in mucosal melanoma patients. Mural plans to increase the size of this cohort by approximately 16 patients (to a total of approximately 90 patients) and expects a top-line data readout in the first half of 2025.
ARTISTRY-7 is a potentially registrational, phase 3 trial evaluating nemvaleukin as a monotherapy and in combination with pembrolizumab in patients with platinum-resistant ovarian cancer. Mural plans to increase the trial by approximately 56 patients (to a total of approximately 448 patients) and to change the primary endpoint of the trial from progression free survival (PFS) to overall survival (OS), which Mural believes is a more clinically meaningful outcome and one typically preferred by both regulators and payers. An OS endpoint may also better capture the effects of an IO doublet combination therapy as compared to a PFS endpoint. Mural projects an interim OS readout in the first quarter of 2025 based on approximately 75% of events and a final OS readout in the second quarter of 2026.
"Since I joined Mural six months ago, we have assembled a group of world class oncology experts across our management team and our board of directors who are complemented by our seasoned in-house team. Together we have been thinking critically about the best ways to deliver treatments to patients who desperately need them. We believe expanding patient enrollment in both potentially registrational trials, as well as shifting the primary endpoint of the ARISTRY-7 trial, may result in more meaningful clinical data," said Caroline Loew, Ph.D., Mural’s chief executive officer. "We believe there is enormous potential in our lead candidate, nemvaleukin, and these enhancements are in the best interests of both our future patients and our shareholders."

Mural Oncology spun out of Alkermes and became an independent, publicly traded immuno-oncology company in November 2023. Now led by an experienced and highly accomplished oncology-focused executive team and board of directors, the company is leveraging its core competencies in immune cell modulation and protein engineering. Mural’s lead product candidate, nemvaleukin, is being developed to treat a wide range of solid tumors. Mural is also advancing engineered therapies targeting interleukin-18 and interleukin-12, with plans to nominate development candidates for each program in 2024. The Company’s cash resources of $275 million, as of November 15, 2023, are expected to fund its operations into 4Q 2025.

Monte Rosa Therapeutics Provides Corporate Update and Key Anticipated Milestones for 2024

On January 8, 2024 Monte Rosa Therapeutics (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported anticipated 2024 milestones ahead of its participation in the 42nd Annual J.P. Morgan Healthcare Conference (Press release, Monte Rosa Therapeutics, JAN 8, 2024, View Source [SID1234639090]). The company’s presentation, taking place on Wednesday, January 10, 2024, at 3:00 p.m. PT, will focus on strategic priorities for 2024, including anticipated progress with the ongoing Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors as well as future development plans for MRT-2359 and MRT-6160, its VAV1-directed MGD for autoimmune diseases.

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"2023 was an exciting and highlight-filled year for Monte Rosa Therapeutics, including encouraging interim Phase 1/2 MRT-2359 clinical results, advancement of our VAV1-targeted MGD into IND enabling studies, and initiation of a strategic collaboration with Roche," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Building on last year’s successes, this year we look forward to announcing the RP2D for our MRT-2359 program and initiating multiple Phase 2 expansion cohorts in tumors characterized by high L- and N-MYC expression, with the potential to consider indication expansion into c-MYC-driven tumor types such as ER+ breast cancer and castration-resistant prostate cancer. Our highly selective VAV1-directed MGD MRT-6160 is anticipated to enter a Phase 1 healthy volunteer study this year with the aim to move efficiently into early proof-of-concept studies in patients across multiple autoimmune indications. Lastly, we also expect to nominate additional development candidates in 2024 for programs in both oncology and inflammation/immunology. Our strong balance sheet and cash runway into 1H 2026 positions us to advance our programs through important clinical milestones."

Recap of 2023 Achievements


Presented interim data from the Phase 1/2 clinical trial of MRT-2359 demonstrating tumor reductions in patients with biomarker-positive cancers and favorable pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles.

Announced development candidate MRT-6160, a VAV1-directed MGD, for the treatment of autoimmune diseases, and presented preclinical data demonstrating that MRT-6160 attenuates autoimmune disease progression.

Entered into a strategic collaboration and licensing agreement with Roche to discover and develop novel molecular glue degraders targeting cancer and neurological diseases, with a $50 million upfront payment and eligibility to receive future preclinical, clinical, commercial and sales milestone payments exceeding $2 billion, as well as tiered royalties.

Corporate Updates and Key Anticipated Milestones


Monte Rosa announced today that it has received U.S. Food & Drug Administration Fast Track Designation for MRT-2359 for the treatment of patients with previously treated, metastatic small cell lung cancer (SCLC) with L-MYC or N-MYC expression.

Monte Rosa expects to announce the RP2D for the MRT-2359 Phase 1/2 clinical trial in MYC-driven solid tumors in Q2 2024. Enrollment is ongoing in backfill cohorts at clinically active doses using a 5 days on drug, 9 days off drug schedule. The Company has simultaneously started dose escalation of higher dose density cohorts using a 21 days on, 7 days off schedule.

The Company expects to submit an IND for MRT-6160, a VAV1-targeted MGD, in the first half of 2024 and to initiate a Phase 1 single ascending dose / multiple ascending dose study in healthy volunteers in mid-2024.

The Company expects to nominate a development candidate for the NEK7 preclinical program in Q1 2024.

The Company expects to nominate a development candidate for the CDK2 preclinical program in 2024.

J.P. Morgan Healthcare Conference Presentation

Dr. Warmuth will present Monte Rosa’s pipeline and business updates during a presentation at the 42nd Annual J.P. Morgan Healthcare Conference on Wednesday, January 10, 2024, at 3:00 p.m. PT. A webcast of the presentation will be accessible via the "Events & Presentations" section of Monte Rosa’s website at ir.monterosatx.com, and an archived version will be made available following the presentation.

About MRT-2359

MRT-2359 is a potent, highly selective and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T-and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.

Merck to Acquire Harpoon Therapeutics, Further Diversifying Oncology Pipeline

On January 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Harpoon Therapeutics, Inc. (Nasdaq: HARP) reported that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire Harpoon for $23.00 per share in cash for an approximate total equity value of $680 million (Press release, Merck & Co, JAN 8, 2024, View Source [SID1234639089]).

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"At Merck, we continue to enhance our oncology pipeline through strategic acquisitions that complement our current portfolio and advance breakthrough science to help address the needs of people with cancer worldwide," said Dr. Dean Y. Li, president, Merck Research Laboratories. "This agreement reflects the creativity and commitment of scientists and clinical development teams at Harpoon. We look forward to further evaluating HPN328 in innovative combinations with other pipeline candidates."

Harpoon has developed a portfolio of novel T-cell engagers that employ the company’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform, an engineered protein technology designed to direct a patient’s own immune cells to kill tumor cells, and ProTriTAC platform, applying a prodrug concept to its TriTAC platform to create a therapeutic T-cell engager that is designed to remain inactive until it reaches the tumor.

"At Harpoon, we have always been committed to advancing our cancer immunotherapy candidates to improve the lives of patients. With Merck’s recognized leadership in oncology clinical development and global commercial footprint, our lead candidate, HPN328, is well positioned moving forward," said Julie Eastland, president and chief executive officer, Harpoon Therapeutics. "The talented, passionate and dedicated Harpoon team has made great progress over the past eight years in leveraging our research platform to develop an innovative suite of candidates, and we are pleased that Merck has recognized the significant potential of our pipeline. I want to personally thank all of our key stakeholders, including our entire team at Harpoon, trial participants, physicians and our shareholders, who have supported us."

Harpoon’s lead candidate, HPN328, is a T-cell engager targeting delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors. HPN328 is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727) evaluating the safety, tolerability and pharmacokinetics of HPN328 monotherapy in patients with advanced cancers associated with expression of DLL3. The study is also evaluating HPN328 in combination with atezolizumab in patients with SCLC. In October 2023, Harpoon announced the presentation of positive interim tolerability and response data for HPN328 in certain patients with SCLC and neuroendocrine tumors.

Additional pipeline candidates include HPN217 targeting B-cell maturation antigen (BCMA), currently in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma, and several preclinical stage candidates, including HPN601, a conditionally activated targeting epithelial cell adhesion molecule (EpCAM) for the treatment of certain patients with EpCAM expressing tumors.

Under the terms of the agreement, Merck, through a subsidiary, will acquire all outstanding shares of Harpoon Therapeutics, Inc. for a price per share of $23.00 in cash. The Board of Directors of Harpoon has unanimously approved the transaction. Closing of the acquisition is subject to certain conditions, including approval of the merger by Harpoon’s stockholders, the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, and other customary conditions. The transaction is expected to close in the first half of 2024 and will be accounted for as an asset acquisition. Merck expects to record a charge (non-tax deductible) of approximately $650 million, or approximately $0.26 per share, that will be included in non-GAAP results in the quarter that the transaction closes.

Advisors

Evercore Group L.L.C. acted as financial advisor to Merck in this transaction and Covington & Burling LLP acted as its legal advisor. Centerview Partners LLC acted as financial advisor to Harpoon and Goodwin Procter LLP acted as its legal advisor.

About HPN328

HPN328 targets delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand. HPN328 uses Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform that is designed to recruit a patient’s own immune cells to kill tumor cells. HPN328 is being evaluated as monotherapy and in combination in an ongoing open-label, multicenter two-part study (NCT04471727) to assess the safety, tolerability, and pharmacokinetics in patients with certain advanced cancers associated with expression of DLL3.

In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to HPN328 for the treatment of small cell lung cancer.

About TriTACs

TriTACs are novel investigational T-cell-engaging therapeutic proteins optimized for the treatment of solid tumors. TriTACs have an extended serum half-life and may be manufactured using routine biologic techniques.