On October 25, 2023 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that new pre-clinical data leveraging an mRNA platform to develop in-vivo chimeric antigen receptor macrophage ("CAR-M") will be presented as a late-breaking abstract (#LBA1514) at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting held from Wednesday, November 1, to Sunday, November 5, 2023, in San Diego, California (Press release, Carisma Therapeutics, OCT 25, 2023, View Source [SID1234636343]). Two posters highlighting next-generation enhancements to Carisma’s CAR-M platform, including a custom intronic shRNA approach and data on Engineered Microenvironment Converters (EM-C), will also be presented. Additionally, Carisma will share a trial-in-progress poster overviewing its Phase 1 first-in-human (FIH) study design of its lead program, CT-0508, sharing objectives and eligibility criteria.

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Carisma will participate in the virtual SITC (Free SITC Whitepaper) 2023 Annual Meeting Press Conference on Wednesday, November 1, 2023, from 12:00–1:30 pm PT.

"We are excited to present this pre-clinical data from our collaboration with Moderna for the first time," said Steven Kelly, President and Chief Executive Officer of Carisma. "Over the past year, we have leveraged the expertise of both companies to pioneer the development of in-vivo mRNA/LNP-based cell therapy. The study is exploring the potential for an off-the-shelf treatment approach to enhance therapeutic benefit for patients living with cancer."

Oral & Poster Presentations:

In vivo CAR-M: Redirecting endogenous myeloid cells with mRNA for cancer immunotherapy
Primary Author: Bindu Varghese, PhD
Presentation Type/#: Oral – 1514
Session Date/Time (PT): Friday, November 3, 2023, 11:30 am, Session 104: Late Breaking Abstract Session
CAR-Macrophages with custom intronic shRNA exhibit enhanced efficacy against solid tumors
Primary Author: Chris Sloas, PhD
Presentation Type/#: Poster – 307
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
Engineered Microenvironment Converters (EM-C): Macrophages expressing synthetic cytokine receptors reverse immunosuppressive signals in solid tumors
Primary Author: Chris Sloas, PhD
Presentation Type/#: Poster – 389
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
A Phase 1, First in Human (FIH) study of autologous macrophages engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants (pts) with HER2 overexpressing solid tumors
Primary Author: Kim Reiss, MD
Presentation Type/#: Poster – 635
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
Presentation and posters will be available in the Journal for ImmunoTherapy of Cancer (JITC) supplement once published on Tuesday, October 31, 2023, at 9:00 am ET.

About CT-0508

CT-0508 is a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M). It is being evaluated in a landmark Phase 1 multi-center clinical trial that focuses on patients with recurrent or metastatic HER2-overexpressing solid tumors whose cancers do not have approved HER2-targeted therapies or who do not respond to treatment. Carisma is selecting participants who have tumors of any anatomical origin, but with the commonality of overexpressing the HER2 receptor on the cell surface, which is the target for our CAR-M. The Phase 1 clinical trial marks the first time that engineered macrophages are being studied in humans. The trial continues to enroll patients at seven clinical sites in the U.S., including (i) Penn Medicine’s Abramson Cancer Center, (ii) the University of North Carolina Lineberger Comprehensive Cancer Center, (iii) the City of Hope National Medical Center, (iv) the MD Anderson Cancer Center, (v) the Sarah Cannon Cancer Research Institute, (vi) Oregon Health & Science University and (vii) Fred Hutchinson Cancer Center.

On October 25, 2023 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the first patient in Europe has been dosed in the international multi-centre phase 3 clinical trial (NCT05353257) of the company’s self-developed anti-PD-1 mAb HANSIZHUANG (serplulimab) in combination with chemotherapy and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC) in EU country Latvia (Press release, Shanghai Henlius Biotech, OCT 25, 2023, View Source [SID1234636342]). The co-leading principal investigators are Jinming Yu, an Academician of the Chinese Academy of Engineering (CAE) and the Director of Shandong Cancer Hospital, Ligang Xing, the vice director of Shandong Cancer Hospital, and Ying Cheng, the Director of Jilin Cancer Hospital. Previously, the first patients in China, the U.S., Australia and other countries and regions have been dosed.

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According to GLOBOCAN 2020, lung cancer (LC) is the second most commonly diagnosed and the first mortality cancer around the world. There were 2.2 million new LC cases and 1.8 million new deaths in 2020 worldwide, and LC is still the leading cause of cancer deaths[1]. Small cell lung cancer (SCLC) accounts for 15%–20% of the total number of LC, which is featured by high malignancy, strong invasiveness, early metastasis, and rapid disease progression, with extremely poor prognosis. LC is divided into two stages, including limited stage and extensive stage, and 30%–40% patients are in limited stage at the time of diagnosis. The standard treatment regimens for LS-SCLC are surgery, chemotherapy and concurrent radiotherapy. Traditional chemotherapeutic drugs did not exhibit significant progress in patients with LS-SCLC, and most patients tend to develop drug resistance or rapid relapse[2–4]. The advent of immune checkpoint inhibitors has been proven to bring hope to patients with ES-SCLC but has not yet shown benefit in those with LS-SCLC. Recently, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer for the treatment of ES-SCLC. The company is continuing to explore immuno-oncology therapy for LS-SCLC, with the goal of delivering more effective treatment for patients.

HANSIZHUANG is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of MSI-H solid tumours, non-small cell lung cancer (sqNSCLC) and ES-SCLC and esophageal squamous cell carcinoma (ESCC), and has since seen benefits in 40,000 patients in China. Regarding unmet clinical needs as a core, Henlius covers the full range of first-line treatments of LC. Two global multi-centre phase 3 clinical trials regarding sqNSCLC and ES-SCLC have been conducted in China, Turkey, Poland, Georgia, and other countries and regions, with over 30% of the total enrolled subjects being White, providing more diverse cases for clinical research. ASTRUM-005, the international multi-centre, phase 3 study in patients with ES-SCLC, has been published in The Journal of the American Medical Association (JAMA), one of the top four medical journals in the world, making ASTRUM-005 became the first study published in JAMA on SCLC immunotherapy. Moreover, HANSIZHUANG has been granted orphan-drug designations for the treatment of SCLC by the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively. The European Medicines Agency (EMA) has validated the application for HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC. It is worth mentioning that the first patient has been dosed in a bridging head-to-head trial in the US to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, which is expected to propel the product towards US market approval further.

In the future, the company will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of serplulimab and international commercialization process to benefit more patients around the world.

About NCT05353257

This randomised, double-blind, multi-centre, phase 3 clinical study aims to compare the efficacy and safety of serplulimab versus placebo, in combination with chemotherapy (carboplatin/cisplatin-etoposide) and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC). Eligible patients will be randomised at a ratio of 1:1. The primary objective of this study is to evaluate the anti-tumour activity of serplulimab plus chemotherapy and concurrent radiotherapy in LS-SCLC patients. The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) assessed by investigators per RECIST 1.1, as well as safety and immunogenicity.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 4 indications are approved for marketing in China, 1 marketing application is under review in the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). Its marketing applications of the first-line treatment for ES-SCLC are under review by the EMA. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial approvals in China, the U.S., the EU and other countries and regions to initiate more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,600 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine and the British Journal of Cancer, respectively. Furthermore, HASIZHUANG was recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.

On October 25, 2023 Qilu Pharmaceutical reported the latest findings from a multicenter, single-arm Phase II clinical trial at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023 (Press release, Qilu Pharmaceutical, OCT 25, 2023, View Source [SID1234636341]). This trial studied the use of QL1706 (iparomlimab and tuvonralimab) in combination with chemotherapy, with or without bevacizumab, as a first-line treatment of recurrent or metastatic cervical cancer (r/mCC). Professor Danbo Wang from Liaoning Cancer Hospital & Institute reported these findings.

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The study results indicated that using QL1706 in combination with chemotherapy, with or without bevacizumab, as a first-line treatment for r/mCC showed a promising objective response rate (ORR) and survival benefits. Moreover, the treatment exhibited a manageable safety profile without any new safety signals observed, making it a potential new first-line treatment option for r/mCC patients.

I. Research Background

Currently, the preferred standard first-line treatment for r/mCC patients is cisplatin or carboplatin and paclitaxel plus bevacizumab, and efficacy and safety of the treatment also need to be considered. For r/mCC patients with positive PD-L1 expression, the PD-1 inhibitor pembrolizumab, administered with chemotherapy and with or without bevacizumab, is recommended as the standard first-line treatment. Immunotherapy combined with chemotherapy has now become the standard care for r/mCC [1-2]. The latest results from the KEYNOTE-826 study showed that the median progression-free survival (PFS) of PD-L1-positive (CPS ≥1) r/mCC treated with immunotherapy-chemotherapy-pembrolizumab, with or without bevacizumab, increased from 8.2 months to 10.4 months. Furthermore, the median overall survival (OS) extended from 16.5 months to 28.6 months. While the PD-1 inhibitor combined with chemotherapy have significantly improved patient survival compared to chemotherapy alone, the survival benefits for patients remain limited, indicating an unmet clinical need [3-4].

II. Study Design

This study enrolled r/mCC patients who had not undergone systemic therapy. These patients were treated with either QL1706-chemotherapy (Cohort 1) or QL1706-chemotherapy-bevacizumab (Cohort 2) until disease progression, the occurrence of intolerable toxicity or the patient’s withdrawal of informed consent. The primary endpoint of the study was safety. Secondary endpoints included ORR, duration of response (DOR), disease control rate (DCR), PFS, which were assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and OS. The study design is illustrated in Figure 1.

III. Study Results

A total of 60 patients were enrolled to cohort 1 and cohort 2, 30 patients in each cohort. Patients in cohort 1 were treated with QL1706 monoclonal antibody combined with either cisplatin or carboplatin and paclitaxel. Patients in Cohort 2 received the same regimen as the first but with addition of bevacizumab. The mean age of the patients was 52.0 years, with 58.3% having an ECOG Performance Status of 1. Squamous cell carcinoma was the pathological type in 78.3% of the patients, while recurrent CC was found in 86.7%.

As of April 24, 2023, the median follow-up was 14 months. Out of 58 patients who received at least one post-baseline efficacy evaluation, ORR was 81.0% (95% CI, 68.6-90.1). Among these patients, eight achieved complete response (CR) and 39 achieved partial response (PR). The DCR was 98.3% (95% CI, 90.8-100.0). The median PFS reached 14.3 months (95% CI, 9.2 months to not estimable), while the median OS had not yet been reached. In cohort 2, with combination treatment of bevacizumab, the median PFS was 16.4 months. (Figure 2)

In terms of safety, treatment-related adverse events (TRAEs) were observed in all patients, with a 71.7% incidence of grade 3 or higher adverse events. The most common TRAEs included white blood cell count decreased (71.3%), neutrophil count decreased (68.3%), and anemia (43.3%). The incidence of treatment-related serious adverse events was 30%; the occurrence of immune-related adverse events (irAEs) was 13.3%; TRAEs leading to discontinuation of therapy occurred in 26.7% of patients; and the incidence of treatment-related deaths was 1.7%, possibly related to bevacizumab (Figure 3).

IV. Summary

The results of this study demonstrated that the first-line treatment of r/mCC with QL1706 combined with chemotherapy, with or without bevacizumab, showed promising efficacy and favorable safety, regardless of level of PD-L1 expression.

Based on these findings, a Phase III clinical trial of QL1706 in combination with chemotherapy, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic CC is currently ongoing. Furthermore, the New Drug Application (NDA) for the treatment of r/mCC patients who have failed at least one first-line standard platinum-based therapy with QL1706 was accepted by the Center for Drug Evaluation (CDE) in August of this year.

References:

1. Guidelines Working Committee of the Chinese Society of Clinical Oncology. Guidelines for the Diagnosis and Treatment of Cervical Cancer [M]. 2023. Beijing: People’s Medical Publishing House, 2023:70.

2. Tewari KS, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. doi: 10.1056/NEJMoa1309748. Erratum in: N Engl J Med. 2017 17;377(7):702.

3. Colombo N, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 11;385(20):1856-1867.

4. J Clin Oncol 41, 2023 (suppl 16; abstr 5500).

On October 25, 2023 Moderna presented its corporate presentation (Press release, Moderna Therapeutics, OCT 25, 2023, View Source [SID1234636340]).

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On October 25, 2023 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported preliminary Monjuvi U.S. Net Product Sales and Gross Margin for the third quarter of 2023 and provided an update to its financial guidance for 2023 (Press release, MorphoSys, OCT 25, 2023, View Source [SID1234636339]).

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Preliminary Monjuvi (tafasitamab-cxix) U.S. Net Product Sales are US$ 23.4 million (€ 21.5 million) for the third quarter of 2023 and US$ 67.8 million (€ 62.6 million) for the first nine months of 2023, a 5% and 6% increase from the same periods in 2022, respectively (US$ 22.2 million in Q3 2022 and US$ 64.1 million in the first nine months of 2022). Preliminary Gross Margin for Monjuvi U.S. Net Product Sales for Q3 2023 is 65%, due to the recognition of one-time write-offs for raw material used in the production of Monjuvi.

For the full year of 2023, MorphoSys now expects Monjuvi U.S. Net Product Sales to be US$ 85 to US$ 95 million (previously: US$ 80 to US$ 95 million) and Gross Margin for Monjuvi U.S. Net Product Sales to be approximately 75% (previously: 75% to 80%). All other aspects of the guidance for 2023 remain unchanged.

"Sales of Monjuvi continue to be on track for it’s approved indication in relapsed or refractory diffuse large B-cell lymphoma, and give us confidence to narrow our guidance target," said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. "We remain in a solid financial position and continue to be highly judicious with our expenses even as we progress our phase 3 trials, including preparations for the pivotal MANIFEST-2 trial that will read out later this year."

The previous financial guidance for 2023 was provided by MorphoSys on January 5, 2023 and was last reiterated on August 9, 2023 and can be found at www.morphosys.com.

Full financial results for the third quarter of 2023 will be published on November 15, 2023, followed by a conference call on November 16, 2023.

Full Year 2023 Financial Guidance:

Updated 2023 Financial Guidance Previous 2023 Financial Guidance 2023 Guidance Insights
Monjuvi U.S. Net Product Sales US$ 85m to 95m US$ 80m to 95m 100% of Monjuvi U.S. product sales are recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte.
Gross Margin for Monjuvi U.S. Net Product Sales Approx. 75% 75% to 80% 100% of Monjuvi U.S. product cost of sales are recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte.
R&D expenses € 290m to 315m € 290m to 315m 2023 anticipated to be incrementally higher than 2022 due to the expansion of the pelabresib development program.
SG&A expenses € 140m to 155m € 140m to 155m 45% to 50% of mid-point of SG&A expenses represent Monjuvi U.S. selling costs of which 100% are recorded in MorphoSys’ income statement. Incyte reimburses MorphoSys for half of these selling expenses.