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

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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.
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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.
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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

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

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.

On January 8, 2024 MaxCyte, Inc., (NASDAQ: MXCT; LSE: MXCT), a leading, cell-engineering focused company providing enabling platform technologies to advance the discovery, development and commercialization of next-generation cell therapeutics and innovative bioprocessing applications, reported a preliminary update on financial results for the fourth quarter and full year ended December 31, 2023 (Press release, MaxCyte, JAN 8, 2024, View Source [SID1234639088]).

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Preliminary Unaudited Fourth Quarter and Full Year 2023 Results

Total revenue for the fourth quarter of 2023 is expected to be between $15.5 million and $15.7 million, compared to $12.4 million in the fourth quarter of 2022.

● Core revenue is expected to be between $7.0 million and $7.2 million, compared to $10.6 million in the fourth quarter of 2022.
● Strategic Platform License (SPL) Program-related revenue is expected to be approximately $8.5 million, compared to $1.9 million in the fourth quarter of 2022.

Total revenue for the fiscal year of 2023 is expected to be between $41.1 and $41.3 million, compared to $44.3 million for fiscal year 2022.

● Core revenue is expected to be between $29.6 million and $29.8 million, compared to $39.6 million for fiscal year 2022.
● SPL Program-related revenue is expected to be approximately $11.4 million, compared to $4.6 million for fiscal year 2022.

Total cash, cash equivalents, and investments as of December 31, 2023 is expected to be approximately $210 million.

"MaxCyte reported preliminary revenue above our updated total revenue guidance provided in December. The operating environment in the Cell Therapy industry was challenging in 2023; however, we remain confident in the opportunity that exists for MaxCyte in the years ahead," said Maher Masoud, President and CEO of MaxCyte. "In 2023, we supported our partner, Vertex Pharmaceuticals Inc., in the approval of CASGEVY, the first non-viral cell therapy product approved by the FDA. This milestone ushers in a new era of engineered cell therapies to treat diseases and validates the value of our platform. We are committed to supporting our partners in their commercial journeys and the profound impact they will make in patients’ lives."

MaxCyte’s fourth quarter and full year results are preliminary and unaudited and subject to change in connection with the completion of MaxCyte’s quarterly and year-end closing processes and the preparation of its audited financial statements for the quarter and fiscal year ended December 31, 2023. As a result, these preliminary results may differ from the actual results that will be reflected in MaxCyte’s consolidated financial statements for the quarter and fiscal year ended December 31, 2023, which are expected to be released in March 2024 and will be included in MaxCyte’s Annual Report on Form 10-K.

On January 8, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumors, reported a restructuring of its clinical programs and a strategic prioritization of its multi-tumor associated antigen (multiTAA)-specific T cell product pipeline (Press release, Marker Therapeutics, JAN 8, 2024, View Source [SID1234639087]). In addition, the Company reported a clinical update on the Phase 2 ARTEMIS study investigating MT-401, a multiTAA-specific T cell product, for the treatment of patients with acute myeloid leukemia (AML).

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Following the non-dilutive transaction with Cell Ready (Press Release, May 1, 2023), Marker has made significant progress on clinical and corporate restructuring with the objective of accelerating the commercial development of our unique multiTAA technology. The Company reported the prioritization of MT-601 in chimeric antigen receptor (CAR) relapse patients with lymphoma (APOLLO; clinicaltrials.gov identifier: NCT05798897). This strategic decision was made based on 1) the Company’s promising non-clinical and clinical data using the multiTAA technology in lymphoma, and 2) the lack of an approved treatment for patients who experience relapse after treatment with CD19 CAR T (up to 60% within a year; Chong EA et al, N Engl J Med, 2021), which is a clear unmet medical need and provides an opportunity for accelerated product development.

Highlights from the Lymphoma Study

Clinical Efficacy in Patients with Lymphoma in Previous Clinical Trial

· The multiTAA-specific T cell product targeting 5 TAAs was investigated in the TACTAL study, a Phase 1 trial conducted at Baylor College of Medicine.
· The TACTAL study enrolled patients with Hodgkin’s and non-Hodgkin’s lymphoma and demonstrated clinical safety and efficacy with durable clinical responses for 6 years (Vasileiou et al, J Clin Oncol, 2021).

Non-Clinical Proof-of-Concept Data

· Marker developed a long-term in vitro killing assay 1) to better understand resistance mechanisms following CAR T cell treatment and 2) to determine if a product that is capable of targeting 6 TAAs (MT-601) will be able to kill CAR-resistant lymphoma cells (Press Release, May 31, 2023).
· After CD19-targeting CAR T cell treatment, 98% of lymphoma cells were eliminated in vitro. Long-term follow-up (three weeks) demonstrated outgrowth of CD19-negative tumor cells. Additional anti-CD19 CAR T cell treatment failed to inhibit tumor growth due to the lack of target antigen (CD19) expression on the tumor.
· Treating CAR-resistant lymphoma cells with MT-601 resulted in complete long-term growth inhibition (over three weeks) highlighting that MT-601 has the potential to effectively treat CD19 CAR-resistant tumors (Pre-Clinical Data in Lymphoma, May 31, 2023).

Durable Response in CAR Relapsed Patient with Lymphoma

· The Company-sponsored Phase 1 APOLLO study investigates the safety and efficacy of MT-601 in patients with lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell therapy.
· The first study participant, a 57-year-old female with diffuse large B cell lymphoma (DLBCL), was enrolled in the Phase 1 dose escalation stage of the trial after failing 4 prior lines of therapy, including anti-CD19 CAR T cell therapy (Press Release, June 12, 2023). The participant relapsed within 90 days of CAR T cell therapy, and was treated with MT-601 without prior lymphodepletion.
· The patient tolerated MT-601 well without treatment-related adverse events and achieved a complete response eight weeks after the second infusion of MT-601 (Press Release, Sep 11, 2023).
· Six months following treatment with MT-601 the study participant has maintained a complete response to treatment suggesting that MT-601 is more durable compared to CAR T cells in this study participant (Press Release, Dec 11, 2023).

CD19-targeting CAR T cell therapies are associated with severe side effects and toxicities, and up to 60% of patients with DLBCL relapse within a year (Chong EA et al, N Engl J Med, 2021). Additionally, the FDA is investigating CAR T therapies for the potential risk of inducing secondary cancers (U.S. Food and Drug Administration, Nov 28, 2023). To date, multiTAA-specific T cell therapies have been well-tolerated in over 200 patients in clinical trials, and Marker believes that, unlike CAR T cells, multiTAA-specific T cells could represent a safer therapeutic option due to their non-genetically engineered approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood without the risk of mutagenesis.

Promising Clinical Observations and New Directions with MT-401 in Patients with MRD in AML

Today, Marker is providing a clinical update on the Phase 2 ARTEMIS clinical study (clinicaltrials.gov identifier: NCT04511130), and the direction it will pursue. This multicenter study is evaluating the safety and efficacy of MT-401 in patients with AML after allogeneic hematopoietic stem cell transplantation (HSCT).

A total of 8 patients with MRD+ AML after HSCT were enrolled and treated with MT-401. None of the 8 treated patients experienced a drug related adverse event. Of the 8 treated patients, 4 experienced a clinical benefit, with 3 showing a conversion to MRD-negative, and one patient showing a partial response with a logarithmic reduction of MRD levels by PCR. One patient has not yet had the first assessment post treatment. Of the 8 treated patients in the study, only 1 patient had documented disease progression and was taken to a second transplant. The other 3 patients were taken off the study for reasons unrelated to the clinical outcome.

Obtaining timely consent and re-accessing HSCT donors for apheresis for the manufacture of MT-401 caused delayed patient accrual and patient eligibility issues. Consequently, the rapid progression of disease contributed to some patients to withdraw from the study prior to administration of study product. Therefore, to streamline resources and to reduce time to treatment, Marker intends to focus on a ready for use product from commercially available leukapheresis material and will discontinue the patient-specific part (ARTEMIS) of the AML program.

"We are encouraged by the clinical observations in patients with MRD in our AML study," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "The data demonstrate the safety of MT-401 and provide evidence that MT-401 could benefit patients with MRD+ AML."

Dr. Vera continued: "Decreasing the time to treatment is critical when it comes to the treatment of patients that suffer from rapidly progressing cancers, such as patients with MRD in AML, which typically advances rapidly into frank relapse with poor outcomes. We believe using commercial leukapheresis material from healthy donors can bypass the bottleneck associated with donor identification and facilitate large-scale manufacturing. This approach is expected to not only reduce manufacturing costs, but also expedite time to treatment to as little as 72 hours. We are currently working to initiate the clinical study and anticipate that the first patient with AML will be treated with MT-401 manufactured from healthy donors in the second half of 2024."

The Company previously announced that the FDA has cleared the clinical protocol to investigate a ready for use MT-401 product manufactured from healthy donors in patients with AML, and a cellular inventory has been established with continuous efforts to expand this inventory (Press Release, Aug 7, 2023).

Marker has secured non-dilutive funding to support the clinical investigation of a ready for use MT-401 product in patients with AML. Using these allocated funds will allow the Company to proceed with the ready for use program without affecting the ongoing Phase 1 APOLLO study and the capital runway of the Company into the fourth quarter of 2025.

In addition, the Company has an Investigational New Drug (IND) application cleared by the U.S. FDA for a Phase 1 trial to investigate MT-601 in patients with pancreatic cancer in combination with first-line chemotherapy. The clinical advancement of this multicenter study will be pending additional funding from non-dilutive sources, including grant activities.

"The strategic restructure of our multiTAA pipeline reflects our ongoing commitment to innovate and deliver groundbreaking treatments," said Dr. Vera. "The decision to shift our focus on MT-601 in patients with lymphoma is based on our promising non-clinical and clinical observations. Lymphoma is a highly competitive landscape with numerous companies striving to compete with CAR T cell therapies. However, our approach differs by targeting multiple antigens and focusing on a unique niche: patients who have experienced CAR T cell relapse or are ineligible for CAR T therapy."

Dr. Vera continued: "We believe that MT-601 could address the unmet medical need in this patient population. Developing a product in this patient population is commercially attractive due to the well understood natural history, the unmet medical need, and the lower number of competing trials. Assuming we continue to see promising results in our APOLLO study, this would allow us to accelerate the development of MT-601 in CAR relapse patients with lymphoma."

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 200 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated and demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect.

On January 8, 2024 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing, manufacturing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company’s management will participate in the following upcoming investor conference (Press release, MacroGenics, JAN 8, 2024, View Source [SID1234639086]):

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42nd Annual J.P. Morgan Healthcare Conference. MacroGenics’ President & Chief Executive Officer, Scott Koenig, M.D., Ph.D., will provide a corporate overview on Thursday, January 11, 2024, at 7:30 am PT. Management will also participate in one-on-one meetings.
A webcast of the above presentation may be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source The Company will maintain an archived replay of this webcast on its website for 30 days after the conference.