Carisma Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of CT-0525, a Novel HER2-Targeting CAR-Monocyte

On May 16, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that the first patient was dosed in its Phase 1 clinical trial evaluating CT-0525, an ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy, for the treatment of patients with solid tumors that overexpress human epidermal growth factor receptor 2 (HER2) (Press release, Carisma Therapeutics, MAY 16, 2024, View Source [SID1234643411]).

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"Dosing of the first patient in the CT-0525 Phase 1 trial is a significant step in the development of engineered myeloid cells, marking the first time a CAR-Monocyte is tested in humans in the solid tumor setting," said Eugene P. Kennedy, M.D., Chief Medical Officer of Carisma. "Our pre-clinical data leads us to believe that this next-generation approach of our CAR-M platform has the potential to have a greater impact on patients than our initial CAR-Macrophage program, particularly through faster manufacturing, higher dosing, and increased potency, persistence, and tumor infiltration. We look forward to progressing this trial and expect to report initial data by the end of 2024."

"Patients battling HER2-overexpressing solid tumors face an urgent need for new therapeutic options, as disease progression is a common challenge," commented Davendra Sohal, M.D., M.P.H., Professor of Medicine at the University of Cincinnati Cancer Center. "CT-0525 introduces a differentiated approach to potentially address this shortcoming, offering hope for HER2-positive cancer patients. We are proud to be the first site to treat a patient with CT-0525 and look forward to continuing to collaborate with Carisma and other cancer centers to rapidly enroll patients in the Phase 1 trial."

The Phase 1 clinical trial for CT-0525 is an open-label study designed to assess the safety, tolerability, and manufacturing feasibility of CT-0525. This trial will enroll participants with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 whose disease has progressed on standard approved therapies. The study will consist of two dose escalation cohorts. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06254807.

Carisma will present a Trial in Progress poster outlining the design of the CT-0525 Phase 1 trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting, scheduled to take place from May 31 to June 4, 2024, in Chicago, IL.

About CT-0525

CT-0525 is a first-in-class, ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). It is being studied in a multi-center, open label, Phase 1 clinical trial for patients with advanced/metastatic HER2-overexpressing solid tumors that have progressed on available therapies. The CAR-Monocyte approach has the potential to address some of the challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity. CT-0525 has the potential to enable significant dose escalation, enhance tumor infiltration, increase persistence, and reduce manufacturing time compared to macrophage therapy.

INTERIM MANAGEMENT STATEMENT Q1 2024 OF MOLECULAR PARTNERS: PIPELINE PROGRESSING WITH TWO ADDITIONAL PROGRAMS TO ENTER THE CLINIC IN 2025, UPDATE TO MP0533 PROGRAM

On May 16, 2024 Molecular Partners AG, a clinical-stage biotech company pioneering the design and development of DARPin therapeutics for medical challenges that other drug modalities cannot readily address ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the first quarter of 2024 (Press release, Molecular Partners, MAY 16, 2024, View Source [SID1234644825]).

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"This quarter we demonstrated continued progress across our clinical and preclinical pipeline with preparations underway for two new clinical candidates and first-in-human data for our Radio DARPin platform in 2025," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "Building on encouraging initial data and clinical activity, MP0533 dose escalation will expand and now explore higher potential doses, to see what the true clinical impact can be and which patient subpopulations can benefit most. We plan to share data from these higher dose clinical cohorts starting in the second half of this year. For our emerging pipeline, we plan to announce preclinical data from our Switch-DARPin Platform at EHA (Free EHA Whitepaper) and anticipate translational efficacy data in the second half of 2024. Our lead Radio-DARPin candidate is advancing into IND-enabling studies in collaboration with our partner Orano Med, with initiation of clinical studies planned for 2025 and pre-clinical data to be presented at SNMMI in June 2024."

Financial and Business Outlook

For the full year 2024, at constant exchange rates, the Company expects total operating expenses of CHF 70-80 million, remaining consistent with the prior year. Of this figure, approximately CHF 8 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation.

With CHF 174.1 million in cash and short-term time deposits and no debt as of March 31, 2024, the Company expects to be funded well into 2026. This guidance does not include any potential receipts from R&D partnerships.

Research & Development Highlights

MP0533: Clinical update and planned dose escalation expansion
MP0533 (CD33 x CD123 x CD70 x CD3), a novel tetra-specific T cell-engaging DARPin, is currently being evaluated in a Phase 1/2a clinical trial for patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome/AML (MDS/AML) (NCT05673057).

Results presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2023 from the first 11 patients treated with MP0533 indicated a favorable safety profile across the first four dosing regimens (DRs), with no dose-limiting toxicities observed. The study is on track with DR 7 enrollment complete and dosing currently ongoing. Based on the current MP0533 safety data and discussion with treating physicians and key opinion leaders, a protocol amendment was filed on April 25, 2024 to expand enrollment to higher dose cohorts (DRs 8-11) for further characterization of the MP0533 dose-response. The company expects to enroll patients in higher cohorts seamlessly in the second half of 2024.

The mechanism of action of MP0533 is designed to preferentially kill AML cells (blasts and leukemic progenitor and stem cells) that express any combination of the cell surface antigens CD33, CD123, and CD70, while sparing healthy cells which tend to express only one or none of these targets. Updated data, with cut-off as of March 12, 2024, show that MP0533 continues to demonstrate clinical activity similar to what has been reported in earlier dose cohorts. In DRs 5 and 6, an additional 17 patients were treated with MP0533, and of these, 2 patients reached ELN criteria of Morphological Leukemia Free State (MLFS), with additional patients showing early blast reductions in the bone marrow. The drug safety profile remains acceptable with the majority of adverse events reported as infusion-related reactions and cytokine release syndrome. The current data supports expansion to higher dose cohorts to explore the activity of MP0533 in a highly heterogeneous r/r AML patient population. Diverse parameters (e.g., leukemic stem cells, clonal evolution, immune activation) are being examined to inform the next development steps including the potential of earlier lines of treatment, and combination settings. The Company anticipates providing a next clinical update from the study in the second half of 2024 at a scientific congress.

Radio-DARPin Therapy Platform
Molecular Partners continues to advance its RDT platform and programs. At the J.P. Morgan Healthcare Conference in January 2024, the company presented data demonstrating successful increase of tumor uptake and reduction of kidney absorption by applying novel engineering approaches to modify the DARPin backbone (Stealth-DARPins) and its half-life. This enabled further internal progress of the RDT platform and pipeline expansion.

Also in January 2024, Molecular Partners entered a strategic collaboration with Orano Med to co-develop 212Pb-based RDTs for patients with solid tumors. The collaboration combines the power of DARPins, as a highly differentiated modality for tumor-targeted delivery of radioisotopes, with Orano Med’s leading capabilities in Targeted Alpha Therapy and supply, to further advance the RDT platform and expand Molecular Partners’ RDT portfolio.

The tumor-associated protein Delta-like ligand 3 (DLL3) was selected as the target of the Company’s lead RDT program to be advanced into IND-enabling studies in the first half of 2024. The initiation of clinical studies and first-in-human data for our RDT platform are expected in 2025 through co-development with Orano Med.

Molecular Partners will provide an update in an oral presentation at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2024 in Toronto on June 11.

Abstract Title: Lead-212 Radio-DARPin Therapeutic (RDT) targeting delta-like ligand 3 (DLL3) shows promising preclinical antitumor efficacy and tolerability in small cell lung cancer (SCLC)

Session Title: Integrated Session: Radionuclides (CMIIT/RPSC)
Presentation Timing: June 11, 2024; 8:00-9:15 am local time

Molecular Partners also expects to nominate additional targets and RDT candidates in 2024.

In addition, Molecular Partners continued to progress its RDT portfolio of projects in partnership with Novartis.

Switch-DARPin Platform

The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. The objective is conditional activation of a targeted immune response. The first Switch-DARPin program (cKIT x CD16a x CD47) was introduced at the annual J.P. Morgan Healthcare Conference in January 2024. This approach is designed to induce exhaustive killing of hematopoietic stem cells as next-generation conditioning regimen to increase long-term disease control post hematopoietic stem cell transplant (HSCT) for AML patients, including those with a poor cytogenetic risk profile, and those currently not eligible for standard high-intensity conditioning. Our intent is to extend the access to potentially curative HSCT for more patients with AML as well as additional hematologic malignancies, and genetic diseases requiring HSC transplant.

The company will present initial preclinical data at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2024 in Madrid on June 14 and has planned preclinical proof-of-concept studies for the second half of 2024.

EHA 2024 Abstract Title: C-KIT X CD16a X CD47 Switch-DARPin with conditional blockade of CD47: a next-generation targeted conditioning for hematopoietic stem cell transplantation

Session Title: Stem Cell Transplantation – Experimental
Abstract Number for Publication: P1294
Poster Session Timing: June 14, 2024; 6-7 pm CET

MP0317: Final Phase 1 data at ASCO (Free ASCO Whitepaper)

MP0317 simultaneously targets CD40 and fibroblast activation protein (FAP) to enable tumor-localized immune activation. The phase 1 dose-escalation study of MP0317 in patients with advanced solid tumors (NCT05098405) was completed in January 2024. The final outcomes of the 46 treated patients will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024 in Chicago, IL on June 1.

Abstract Title: Effect of MP0317, a FAP x CD40 DARPin, on safety profile and tumor-localized CD40 activation in a phase 1 study in patients with advanced solid tumors.

Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: 2573
Poster Session Timing: June 1, 2024 from 9:00 am CDT (Hall A)

Corporate and Management Highlights
On February 5, 2024 a putative class action complaint against the Company, its directors, and certain of its executive officers was dismissed without prejudice in the Company’s favor, and the plaintiff filed a stipulation of dismissal with prejudice on February 23, 2024. The case was ordered closed on February 29, 2024. The original case was filed on July 12, 2022 in the U.S. District Court for the Southern District of New York.

At the Company’s Annual General Meeting on April 17 2024, all motions proposed by the Board of Directors at the Annual General Meeting were approved by the shareholders of the Company.

Financial Calendar

August 26, 2024 – Publication of Half-year Results 2024 (unaudited)

October 31, 2024 – Interim Management Statement Q3 2024

Oncopeptides presents new data highlighting treatment benefits of Pepaxti in high-risk multiple myeloma patients at the COMy Congress

On May 16, 2024 Oncopeptides, a biotech company focused on difficult-to-treat cancers, reported that new scientific data on melflufen, branded in Europe as Pepaxti, has been accepted at the 10th annual World Congress on Controversies in Multiple Myeloma (COMy), to be held on May 23-26 (Press release, Oncopeptides, MAY 16, 2024, View Source [SID1234646777]). The study, published by a team from institutions across Europe, including the University of Würzburg and the Institute for Molecular Medicine Finland, focuses on the effectiveness of melflufen and shows promising results for the drug when treating patients with a particularly challenging form of multiple myeloma.

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The study will be presented to congress attendees through an online oral presentation on May 26. The presentation will be given by Caroline Heckman, from the Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship at the University of Helsinki.

Multiple myeloma can be especially difficult to treat in patients who have specific genetic mutations or deletions, such as del(17p) and/or mutations in the TP53 gene. These genetic characteristics are associated with a poorer prognosis and shorter survival rates.

The research findings indicate that melflufen is more effective than traditional alkylating agents causing DNA damage and promoting the death of cancer cells lacking a functional so-called p53 protein, which is a common issue in high-risk multiple myeloma cases. The study also highlighted significant changes in gene expression that enhance the drug’s impact on cancer cells. Furthermore, patients with the del(17p) genetic abnormality treated with melflufen and dexamethasone showed a longer progression-free survival and higher overall response rate compared to those treated with pomalidomide and dexamethasone in the OP-103 OCEAN trial.

"These findings support the potential of melflufen as a valuable treatment option for patients with relapsed or refractory multiple myeloma, and it is encouraging to see that it has the potential to support patients who present high-risk genetic profiles," says Stefan Norin, Chief Medical Officer at Oncopeptides. "The study underscores the ongoing need for therapies that address the specific challenges posed by genetic variations in cancer treatment."

In addition to the above mentioned presentation, two posters will be presented at the congress. The first poster presents "The effect of transplant status on exposure-adjusted AE rates in melflufen-treated RRMM patients in a pooled safety population from 4 studies," and the second poster outlines previously presented findings on the longer-term outcomes from the OCEAN study.

For more information, including questions and answers for investors, please visit Oncopeptides’ website. For more information about the Congress, please visit the COMy website.

Moleculin Abstract Accepted for Poster Presentation at the European Hematology Association (EHA) 2024 Hybrid Congress

On May 16, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported its abstract has been accepted for poster presentation at the EHA (Free EHA Whitepaper)2024 Hybrid Congress being held June 13-16, 2024 in Madrid, Spain and virtually (Press release, Moleculin, MAY 16, 2024, View Source [SID1234643395]).

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Details for the poster presentation are as follows:

Abstract: P537
Session: Acute myeloid leukemia – Clinical
Title: LIPOSOMAL ANNAMYCIN (L-ANN) IN COMBINATION WITH CYTARABINE FOR TREATMENT OF PATIENTS WITH ACUTE MYELOID LEUKAEMIA (AML) REFACTORY TO OR RELAPSED (R/R) AFTER INDUCTION THERAPY (MB-106 STUDY)
Presenting Author: Wolfram C. M. Dempke, MD, PhD, MBA, European Chief Medical Officer of Moleculin

For more information about the EHA (Free EHA Whitepaper)2024 Hybrid Congress, visit the event website.

Compugen Publishes Paper in Cancer Immunology Research on Unique Biology of PVRIG and its Therapeutic Potential

On May 16, 2024 Compugen Ltd. (Nasdaq: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported the online publication of a peer reviewed paper titled "PVRIG is expressed on stem-like T cells in dendritic cell-rich niches in tumors and its blockade may induce immune infiltration in non-inflamed tumors" link, in Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Compugen, MAY 16, 2024, View Source [SID1234643412]).

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"Increasingly, we are observing that an additional component is needed to optimize the anti-tumor response to a combination of an anti-TIGIT and anti-PD-(L)1," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen. "Through our computational discovery work at Compugen we were the first to discover the novel immune checkpoint PVRIG and later presented preclinical data on the potential synergy in blocking PVRIG, TIGIT and PD-1 pathways. Subsequently, we showed in Phase 1 studies, that the triple blockade of PVRIG with our potential first-in-class antibody, COM701 in combination with an anti-TIGIT and anti-PD-1 demonstrated durable clinical responses with a favorable safety profile in indications typically not responding to immunotherapy. These responses were associated with the infiltration and proliferation of cancer-fighting T cells in the tumor microenvironment, atypical for less inflamed indications."

Eran Ophir, Ph.D., Chief Scientific Officer at Compugen added, "Our paper published online today in Cancer Immunology Research provides an advanced understanding of the unique biology of PVRIG and its role in cancer. Using single-cell RNA sequencing and spatial transcriptomic analysis, we showed the differentiated expression of PVRIG and its ligand PVRL2 on early differentiated stem like memory T cells and dendritic cells, respectively, the interaction of which plays an important role in inhibiting the recruitment and proliferation of cancer fighting T-cells in the tumor microenvironment. This unique biology of PVRIG may support a novel approach of potentially overcoming resistance to immunotherapy by sensitizing tumors to respond to other immune checkpoint inhibitors."