On January 10, 2025 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported positive initial clinical data from the Phase 1 dose escalation and backfill cohorts for emiltatug ledadotin (Emi-Le; XMT-1660), Mersana’s lead Dolasynthen ADC candidate targeting B7-H4 (Press release, Mersana Therapeutics, JAN 10, 2025, View Source [SID1234649594]).

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"We believe the initial safety, tolerability and efficacy data for Emi-Le demonstrate a profile that is exciting and differentiated within both the B7-H4 field and the broader ADC landscape," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "We have observed clinical activity across tumors, including in heavily pre-treated patients with TNBC. These clinical data have led us to initiate expansion in patients with TNBC who have previously been treated with at least one topo-1 ADC, a population with very high unmet need."

As of a December 13, 2024 data cutoff, the dose escalation portion of the Emi-Le Phase 1 clinical trial enrolled a total of 130 patients with advanced/metastatic TNBC; hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; ovarian cancer; endometrial cancer and adenoid cystic carcinoma type 1. The enrolled patient population was heavily pretreated, with patients receiving up to 15 and a median of 4.5 prior lines of therapy, and approximately 92% of enrolled patients with TNBC had been previously treated with at least one topo-1 ADC. Among the 103 patients with known B7-H4 tumor expression, approximately 44% had a tumor proportion score of 70% or higher, which Mersana has preliminarily characterized as "B7-H4 high."

Emi-Le was observed to be generally well tolerated, with no Grade 4 or 5 treatment-related adverse events (TRAEs) reported. The most common TRAEs of any grade across the entire patient population were transient aspartate aminotransferase (AST) increase (38% of patients), generally asymptomatic and reversible proteinuria (31%), generally low-grade nausea (29%) and low-grade fatigue (28%). The only Grade 3 TRAEs in ≥5% or more of all patients were AST increase (14%) and proteinuria (9%). Across the entire enrolled patient population, TRAEs leading to discontinuation, dose reduction and dose delay were observed in 2.3%, 9.2% and 12.3% of patients, respectively. No dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia were reported, which the company believes differentiates Emi-Le from many other approved and clinical-stage ADCs.

At intermediate doses in the trial (38.1 mg/m2 to 67.4 mg/m2), the confirmed objective response rate (ORR) among evaluable patients (those with measurable disease at baseline and at least one post-baseline scan) was 23% (6 of 26 patients) across all B7-H4 high tumors and 23% (3 of 13 patients) with B7-H4 high TNBC, all of whom had previously been treated with at least one topo-1 ADC.

In the ASCENT Phase 3 clinical trial of sacituzumab govitecan, a topo-1 ADC, the ORR with standard-of-care single-agent chemotherapy in relapsed/refractory TNBC was approximately 5% with progression free survival of approximately seven weeks. Based on these encouraging Emi-Le data at intermediate doses, Mersana has advanced a dose of 67.4 mg/m2 every four weeks (Q4W) into an expansion cohort in patients with TNBC who have received one to four prior treatment lines, including at least one prior topo-1 ADC.

"In terms of both tolerability and clinical activity, these Emi-Le data are encouraging," Erika Hamilton, M.D., Director Breast Cancer Research, Sarah Cannon Research Institute in Nashville, Tennessee, said, "It is notable that all the TNBC patients who responded to Emi-Le had previously been treated with at least one topo-1 ADC. The results indicate that Emi-Le may help address an already substantial and growing need among topo-1 experienced breast cancer patients for new treatments."

At high doses above 76 mg/m2, the confirmed ORR among evaluable patients was 22% (2 of 9 patients) across all B7-H4 high tumors. Additionally, 78% (7 of 9 patients) had ≥30% tumor reduction in target lesions. At these high dose levels, objective responses in multiple evaluable patients with B7-H4 high tumors were not confirmed after protocol-mandated dose delays for proteinuria. Mersana is implementing proteinuria mitigation efforts and continues to explore higher doses in dose escalation and backfill cohorts to identify a second dose for the expansion portion of the trial.

Mersana’s Expected 2025 Milestones and Areas of Focus

Emi-Le

· 1H2025: Continue enrollment in expansion at a dose of 67.4 mg/m2 Q4W in patients with TNBC who have previously received at least one prior topo-1 ADC
· 2025: Initiate enrollment in expansion at a second dose in patients with TNBC who have previously received at least one prior topo-1 ADC
· 2025: Present additional Phase 1 clinical data from dose escalation and backfill cohorts

XMT-2056, Mersana’s lead Immunosynthen ADC targeting a novel HER2 epitope

· 2025: Present initial clinical pharmacodynamic STING activation data

Pipeline

· Continue to support internal pipeline and existing collaborations with Johnson & Johnson and Merck KGaA, Darmstadt, Germany

Conference Call Information

Mersana will host a conference call today at 8:30 a.m. ET to discuss the initial clinical data from its Phase 1 clinical trial of Emi-Le. To access the call, please dial 833-255-2826 (domestic) or 412-317-0689 (international). A live webcast that includes the data presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com, and a replay of the webcast will be available in the same location following the conference call for approximately 90 days.

On January 10, 2025 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported that Chief Executive Officer Vlad Vitoc, M.D. will present at the Biotech Showcase 2025 investor conference taking place in San Francisco, California January 13-15, 2025 (Press release, MAIA Biotechnology, JAN 10, 2025, View Source [SID1234649611]). Dr. Vitoc will also host one-on-one meetings with investors throughout the 3-day event. The live event will be followed by a virtual 2-day event on January 21-22, 2025.

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At the conference, Dr. Vitoc will discuss MAIA’s recent clinical developments and targeted value-driving milestones for 2025 and beyond, including:

Expansion of MAIA’s THIO-101 pivotal Phase 2 clinical trial to further assess the efficacy of telomere-targeting agent THIO in advanced non-small cell lung cancer (NSCLC) patients receiving third line (3L) therapy.
Multiple THIO trials planned for additional cancer indications.
Significant market opportunity for THIO in the top tumor types globally.
Biotech Showcase conference details:

Dates:

Live event January 13-15, 2025; Digital event January 21-22, 2025

MAIA presentation:

03:00PM PST on Monday, January 13, 2025*

Conference registration:

All-access and Digital passes available on the conference website

One-on-One Meetings:

Bookings available on the conference website

Webcast:

Join here for live presentation and virtual event streaming

On-demand playback:

Available here 2 hours after the presentation, accessible for 6 months

*Please note that the presentation date and time are subject to change. Attendees can refer to the program agenda for conference updates.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a third line of treatment for NSCLC for patients that are resistant to checkpoint inhibitors and chemotherapy.

On January 10, 2025 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported the U.S. Food and Drug Administration (FDA) recently granted an additional Fast Track designation to XMT-1660 (Press release, Mersana Therapeutics, JAN 10, 2025, View Source [SID1234649595]). The company also announced that the World Health Organization has approved emiltatug ledadotin (abbreviated as Emi-Le) as XMT-1660’s international nonproprietary name (INN).

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The new Fast Track designation is for the treatment of advanced or metastatic breast cancer in patients with human epidermal growth factor receptor 2 (HER2) low (IHC 1+ or IHC 2+/ISH–) or HER2-negative (IHC 0) disease, including triple-negative breast cancer (TNBC), who have received a prior topoisomerase-1 inhibitor ADC. Additionally, hormone-receptor positive patients should also have received or be ineligible for endocrine therapy. The FDA previously granted Fast Track designation to Emi-Le for the treatment of adult patients with advanced or metastatic recurrent TNBC.

"Topoisomerase-1 inhibitor ADCs are rapidly becoming the standard of care for metastatic TNBC and hormone-receptor positive breast cancer, and an increasing amount of research shows that these patients are exceedingly difficult to treat thereafter," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "This growing population is a primary focus for us as we advance the development of Emi-Le. We are excited to announce this additional Fast Track designation and the initial clinical data from our ongoing Phase 1 clinical trial that were press released separately this morning."

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drug candidates to treat serious conditions and fill an unmet medical need. A product candidate granted Fast Track designation may be eligible for several benefits, including more frequent meetings and communications with the FDA and, if certain criteria are met, the potential for Accelerated Approval, Priority Review or Rolling Review of a Biologics License Application (BLA) by the FDA.

Conference Call Information
Mersana will host a conference call today at 8:30 a.m. ET to discuss the initial clinical data from its Phase 1 clinical trial of Emi-Le. To access the call, please dial 833-255-2826 (domestic) or 412-317-0689 (international). A live webcast that includes the data presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com, and a replay of the webcast will be available in the same location following the conference call for approximately 90 days.

On January 10, 2025 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported that Chief Executive Officer Vlad Vitoc, M.D. will present at the Biotech Showcase 2025 investor conference taking place in San Francisco, California January 13-15, 2025 (Press release, MAIA Biotechnology, JAN 10, 2025, View Source [SID1234649611]). Dr. Vitoc will also host one-on-one meetings with investors throughout the 3-day event. The live event will be followed by a virtual 2-day event on January 21-22, 2025.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the conference, Dr. Vitoc will discuss MAIA’s recent clinical developments and targeted value-driving milestones for 2025 and beyond, including:

Expansion of MAIA’s THIO-101 pivotal Phase 2 clinical trial to further assess the efficacy of telomere-targeting agent THIO in advanced non-small cell lung cancer (NSCLC) patients receiving third line (3L) therapy.
Multiple THIO trials planned for additional cancer indications.
Significant market opportunity for THIO in the top tumor types globally.
Biotech Showcase conference details:

Dates:

Live event January 13-15, 2025; Digital event January 21-22, 2025

MAIA presentation:

03:00PM PST on Monday, January 13, 2025*

Conference registration:

All-access and Digital passes available on the conference website

One-on-One Meetings:

Bookings available on the conference website

Webcast:

Join here for live presentation and virtual event streaming

On-demand playback:

Available here 2 hours after the presentation, accessible for 6 months

*Please note that the presentation date and time are subject to change. Attendees can refer to the program agenda for conference updates.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a third line of treatment for NSCLC for patients that are resistant to checkpoint inhibitors and chemotherapy.

On January 10, 2025 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported anticipated 2025 milestones ahead of its participation in the 43rd Annual J.P. Morgan Healthcare Conference (Press release, Monte Rosa Therapeutics, JAN 10, 2025, View Source [SID1234649596]). The company’s presentation will focus on strategic priorities, goals, and milestones for 2025. These include anticipated Q1 2025 readouts from its ongoing Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors, the Phase 1 trial of MRT-6160, its VAV1-directed MGD for autoimmune diseases, for which it announced a global license agreement with Novartis in October 2024, and the continued advancement of the Company’s earlier stage programs and QuEEN discovery engine.

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"Last year was transformative for Monte Rosa, with significant validation of our capabilities to design and develop ‘only-in-class’ MGDs for previously undruggable targets across a broad range of disease areas, culminating in the successful licensing of MRT-6160 to Novartis for development across multiple immune-mediated conditions," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We believe this agreement creates substantial value for Monte Rosa by accelerating and broadening the scope of clinical development for MRT-6160, but most of all we believe the deal validates our position as the leading MGD company."

Dr. Warmuth continued, "We enter 2025 in a very strong position with a cash runway that extends into 2028. This enables us to advance our pipeline programs to multiple anticipated clinical data readouts and to further leverage our industry-leading QuEEN discovery engine across areas including immunology and inflammation, cardiovascular, and metabolic diseases. Building on this tremendous momentum, we enter the new year excited to disclose additional Phase 1/2 clinical data for MRT-2359 in patients with MYC-driven solid tumors and initial data from our Phase 1 single and multiple ascending dose trial of MRT-6160, both of which are anticipated in the first quarter of 2025. In addition, Monte Rosa is positioned to advance its third clinical candidate, MRT-8102, into clinical development later this year, and we also expect to nominate development candidates for our CDK2 and second-generation NEK7 programs in the first and second half of the year, respectively."

Recent Program Achievements

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

•
In December, the Company provided a development progress update for the ongoing MRT-2359 Phase 1/2 study, demonstrating a favorable safety profile and targeted levels of GSPT1 degradation using a 21 days on, 7 days off drug dosing schedule in heavily pretreated solid tumor patients. The Company selected a recommended Phase 2 dose (RP2D) of 0.5 mg daily at a 21 days on, 7 days off drug dosing schedule.

MRT-6160, VAV1-directed MGD for immune-mediated conditions

•
In October, the Company announced a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs, including MRT-6160, currently in Phase 1 clinical development for various immune-related conditions. Monte Rosa received a $150 million upfront payment for the agreement. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies, as well as tiered royalties on ex-U.S. net sales. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S.

MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome

•
In September, Monte Rosa presented preclinical data at the Inflammasome Summit demonstrating that its development candidate MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, is a potent, selective, and durable MGD of NEK7. The data provided preclinical proof of concept demonstrating that a NEK7 MGD leads to inhibition of the NLRP3 inflammasome and IL-1 release to reduce the effects of inflammation, supporting the potential to address central and peripheral inflammatory disorders.

CDK2 and Cyclin E1-directed MGD programs

•
In December, at the 2024 San Antonio Breast Cancer Symposium, the Company presented preclinical data on the potential of its highly selective cyclin-dependent kinase 2 (CDK2)-directed molecular glue degrader to treat HR-positive/HER2-negative breast cancer. Data demonstrated deep tumor regression in preclinical models of HR-positive/HER2-negative breast cancer when combined with either a CDK4/6 inhibitor or a CDK4/6 inhibitor and endocrine therapy.
•
In October, at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, Monte Rosa presented preclinical data on the potential of its cyclin E1 (CCNE1)-directed MGDs for the treatment of CCNE1-amplified solid tumors. Cyclin E1 MGDs represent a potential novel therapeutic approach by directly and selectively targeting a frequently amplified non-enzymatic driver oncogene relevant in multiple solid tumors.

QuEEN (Quantitative and Engineered Elimination of Neosubstrates) discovery engine

•
In October, Monte Rosa made a preprint available in BioRxiv entitled, "Mining the Cereblon Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition," which demonstrates a vast expansion of what had been considered druggable within the cereblon target space. Monte Rosa has identified more than 1,600 proteins predicted to be compatible with cereblon across diverse target classes that can potentially be targeted with MGDs.

Key Anticipated Milestones for 2025

•
Share updated data, including biomarker and activity data, from the MRT-2359 Phase 1/2 study in Q1 2025.
•
Report initial data from the Phase 1 SAD/MAD study of MRT-6160 in healthy volunteers in Q1 2025, including data on safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers.
•
Submit an IND application for MRT-8102 in H1 2025.
•
Nominate a development candidate for the second-generation NEK7 program with enhanced CNS penetration in H2 2025.
•
Nominate a CDK2 program development candidate in H1 2025.

Cash Position and Financial Guidance

Unaudited cash, cash equivalents, restricted cash, and marketable securities are expected to be $377.0 million as of December 31, 2024, including the previously announced $150 million upfront payment from Novartis. Based on current cash, cash equivalents, restricted cash, and marketable securities, the Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into 2028.

J.P. Morgan Healthcare Conference Presentation

Dr. Warmuth will present Monte Rosa’s pipeline and business updates during a presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, 2025, at 5:15 p.m. PST. 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 preclinical 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 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. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. Under the terms of an agreement announced in October 2024, Novartis has exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs.

About MRT-8102
MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.

About CDK2 MGDs

Cyclin-dependent kinase 2 (CDK2) is a key driver of cell cycle progression in cancer, acting in coordination with CDK4 and CDK6 to drive cell proliferation. CDK4/6 inhibitors, in combination with endocrine therapy, are FDA-approved agents for the treatment of HR-positive/HER2-negative breast cancer, however many patients become resistant because their tumors become reliant on CDK2. Targeting CDK2 in conjunction with CDK4/6 inhibition has the potential to provide more sustained clinical responses. In preclinical studies, Monte Rosa’s CDK2-targeted MGDs have demonstrated highly selective degradation of CDK2, with no detectable off-target activity, and induced robust downstream CDK2 pathway suppression and drove deep tumor regression in preclinical models of HR-positive/HER2-negative breast cancer when combined with either a CDK4/6 inhibitor or a CDK4/6 inhibitor plus an endocrine therapy. Targeting CDK2 with an MGD represents a potentially novel approach to treating HR-positive/HER2-negative breast cancer in combination with current standard of care therapies.