On April 2, 2024 Kelonia Therapeutics, a biotech company revolutionizing in vivo gene delivery, reported new preclinical data from its lead program KLN-1010, which will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego, California (Press release, Kelonia Therapeutics, APR 2, 2024, View Source [SID1234641724]). KLN-1010, a novel, in vivo CAR-T cell therapy candidate for the treatment of multiple myeloma, which leverages the company’s in vivo Gene Placement System (iGPS) technology, demonstrated that it is safe and effective in preclinical animal models.

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"These data reinforce the best-in-class potential of our in vivo CAR-T cell therapies," said Kevin Friedman, Ph.D., Chief Executive Officer and Founder of Kelonia. "By eliminating the need for ex vivo manufacturing and toxic lymphodepleting chemotherapy, we believe our iGPS technology will remove barriers that currently prevent patients from accessing transformative genetic medicines. We are excited by the preclinical profile of KLN-1010, and are looking forward to advancing this program towards the clinic in the near future."

Diverse T cell lineages, including memory and effector CD4 and CD8 T cells were modified in vivo by KLN-1010 to express a fully human anti-BCMA CAR, without detectable transduction of multiple myeloma tumor cells. A single intravenous injection of KLN-1010 displayed potent anti-tumor efficacy and caused complete tumor regression at multiple dose levels in several preclinical animal models. In other studies, treatment of non-human primates with an iGPS particle expressing an anti-CD20 CAR resulted in potent CAR-T cell activity lasting several months without the need for additional treatments or conditioning chemotherapy.

Details for the poster presentation are as follows:

Title: T cell-specific in vivo transduction with preclinical candidate KLN-1010 generates BCMA directed CAR T cells with potent anti-multiple myeloma activity
Poster Session: Adoptive Cell Therapies 2: CAR-T Cells
Date and Time: April 7, 2024 at 1:30-5:00 pm PT
Location: Section 2
Poster Number: 16

On April 2, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, reported that eight abstracts were selected for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, which will be held from April 5 – 10, at the San Diego Convention Center in San Diego, CA (Press release, BostonGene, APR 2, 2024, View Source [SID1234641723]). BostonGene will exhibit at booth #847.

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BostonGene, together with its collaborators, will deliver presentations on various topics, including the feasibility and utility of using comprehensive genomic and transcriptomic analysis for patients with blood and solid cancers, RNA-based models for TLS prediction in both lung and pancreatic cancers, a transcriptomic-based model to distinguish sarcomatoid features in kidney cancer and the use of comprehensive molecular profiling to evaluate the impact of race and HIV status on the genetic landscape of patients with diffuse large B-cell lymphoma (DLBCL) in southern Africa.

Details of BostonGene’s poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting are below:

1) Title: Comprehensive Genomic and Transcriptomic Analysis to Guide Therapy for Patients with Metastatic Solid Tumors
Abstract number: 939
Date and time: Sunday, April 7, 2024 | 1:30 PM – 5:00 PM
Session title: Application of Precision Medicine for Cancer Care
Location: Poster section 39
Speaker: Burak Uzunparmak, MD, PhD, The University of Texas MD Anderson Cancer Center

This study shows the feasibility and utility of comprehensive molecular profiling to match patients to WES-informed treatments within a clinically relevant time frame. The high rate of additional actionable findings identified by BostonGene’s analytical platform suggest comprehensive testing may offer benefit over traditional targeted panels in solid tumor patients.

Research conducted in collaboration with MD Anderson Cancer Center

2) Title: Test-the-test: Clinical utility of comprehensive whole exome sequencing (WES) and RNA-seq for lymphoma patients
Abstract number: 1754
Date and time: Monday, April 8, 2024 | 9:00 AM – 12:30 PM
Session title: Genomic Characterization of Cancers and Cancer Subgroups
Location: Poster section 17
Speaker: Dai Chihara, MD, PhD, MD Anderson Cancer Center

This study shows an acceptable turnaround time for delivering BostonGene Tumor PortraitTM test reports that include clinically relevant findings and potential clinical trial matches, demonstrating the feasibility of using integrated WES and RNA-seq to guide clinical decision-making in lymphoma patients.

Research conducted in collaboration with MD Anderson Cancer Center

3) Title: Comparative analysis of a predictive transcriptomic model and functional gene expression signatures (FGES) for tertiary lymphoid structure (TLS) detection in lung adenocarcinoma (LUAD)
Abstract number: 6826
Date and time: Wednesday, April 10, 2024 | 9:00 AM – 12:30 PM
Session title: Gene Expression Regulation in the Tumor Microenvironment
Location: Poster section 8
Speaker: Alexander Bagaev, PhD, BostonGene

BostonGene developed a transcriptomic model for TLS detection in LUAD samples that demonstrated improved metrics and prognostic value compared to previously reported TLS FGES, highlighting its potential to guide therapeutic decision-making.

4) Title: Unveiling Heterogeneity of Cancer-Associated Fibroblasts (CAFs) Across Multiple Solid Cancer Types
Abstract number: 291
Date and time: Sunday, April 7, 2024 | 1:30 PM – 5:00 PM
Session title: Stroma Interactions
Location: Poster section 11
Speaker: Boris Shpak, MSc, BostonGene

To evaluate the heterogeneity of stromal cells in various solid cancer diagnoses, single-cell RNA sequencing and bulk RNA-seq data was used. Three consistent cancer-associated fibroblast subtypes were defined, laying the groundwork for a pan-cancer model to characterize stromal cell diversity that could guide efforts in targeting CAFs with anti-tumor therapies.

5) Title: Unraveling sarcomatoid features in clear cell renal cell carcinoma with RNA-seq
Abstract number: 4922
Date and time: Tuesday, April 9, 2024 | 9:00 AM – 12:30 PM
Session title: Artificial Intelligence and Machine/Deep Learning 3
Location: Poster section 36
Speaker: Andrey Shubin, PhD, BostonGene

This presentation describes the robust performance of a BostonGene-developed transcriptomic model in effectively identifying sarcomatoid features in ccRCC samples. With additional investigation, the sarcomatoid ccRCC transcriptomic model can be leveraged to guide checkpoint inhibitor selection for ccRCC patients.

6) Title: An RNA-based model for tertiary lymphoid structure (TLS) prediction and classification in pancreatic adenocarcinoma (PDAC)
Abstract number: 4909
Date and time: Tuesday, April 9, 2024 | 9:00 AM – 12:30 PM
Session title: Artificial Intelligence and Machine/Deep Learning 3
Location: Poster section 36
Speaker: Andrey Tyshevich, MSc, BostonGene

This presentation describes BostonGene’s development of an RNA-based model that stratifies PDAC samples based on TLS status. The results demonstrate an association between TLS-low groups and worse overall survival, offering a method to predict prognoses of PDAC patients based on TLS status.

7) Title: Improved survival and unique mutational signatures in small cell lung cancer arising in patients with limited tobacco use
Abstract number: 3867
Date and time: Tuesday, April 9, 2024 | 9:00 AM – 12:30 PM
Session title: Molecular Biology in Clinical Oncology: Genetics and Beyond
Location: Poster section 41
Speaker: Kyle Concannon, MD, MD Anderson Cancer Center

This presentation describes the use of whole exome sequencing (WES) to uncover targetable mutations in light-smokers with small cell lung cancer (SCLC), highlighting the use of molecular profiling in SCLC patients with minimal tobacco use.

Research conducted in collaboration with MD Anderson Cancer Center

8) Title: Genomic distinctions of HIV- and EBV-associated DLBCL in a diverse African cohort
Abstract number: 786
Date and time: Sunday, April 7, 2024 | 1:30 PM – 5:00 PM
Session title: Epidemiology
Location: Poster section 32
Speaker: Katherine Antel, MD, Dana Farber Cancer Institute

In this study, whole exome and whole transcriptome sequencing was utilized to evaluate the impact of HIV status and Epstein-Barr Virus (EBV) on the genetic landscape, molecular subtypes, and survival outcomes of diffuse large B-cell lymphoma (DLBCL) in a diverse African cohort.

Research conducted in collaboration with Dana Farber Cancer Institute

The abstracts will be published in an online-only Proceedings supplement to the AACR (Free AACR Whitepaper) journal Cancer Research after the conclusion of the AACR (Free AACR Whitepaper) Annual Meeting.

On April 2, 2024 Invenra Inc., an innovative leader in bispecific antibody technology, reported a strategic collaboration with Catalent, a global Contract Development and Manufacturing Organization (CDMO) specializing in innovative drug development solutions (Press release, Invenra, APR 2, 2024, View Source [SID1234641722]). The collaboration will harness the combined expertise and proprietary technologies of Invenra and Catalent to co-discover novel bispecific antibody-drug conjugates.

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Dr. Roland Green, CEO of Invenra, remarks, "We are excited to collaborate with the innovative team at Catalent’s Redwood Bioscience subsidiary. We believe that the combination of Invenra’s B-Body bispecific antibody platform with Catalent’s SMARTag ADC expertise has the potential to unlock synergies and accelerate the development of next-generation cancer therapeutics."

Both companies share a commitment to developing novel therapeutic solutions with the potential to make a meaningful impact in the lives of patients.

On April 2, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported topline data from the Fortis Therapeutics-sponsored Phase 1 study of FG-3246 (also known as FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in a dose-escalation and dose-expansion trial enrolling patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors have progressed on at least one androgen receptor-signaling inhibitor (ARSI) (Press release, FibroGen, APR 2, 2024, View Source [SID1234641721]).

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"We are delighted to showcase the latest encouraging clinical data from the FOR46-001 Phase 1 ADC trial," said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. "We observed a median radiographic progression free survival of 8.7 months in heavily pre-treated patients, who received biologically active doses of FG-3246 in the second line or later setting prior to chemotherapy. These Phase 1 data provide evidence of a favorable safety profile and promising clinical activity as further evidenced by prostate-specific antigen reduction of ≥ 50% and shrinking of measurable disease. We look forward to publishing the totality of the Phase 1 data as we advance the program further in the clinic."

In the Phase 1 dose-escalation portion of the study, ascending dose levels of FG-3246 were administered every 3 weeks. In the dose-expansion arm of the trial, patients were treated at the 2.7 mg/kg adjusted body weight dosing (AjBW) until disease progression. The endpoints were safety, tolerability, and anti-tumor activity as measured by the decline of prostate-specific antigen (PSA) from baseline, objective tumor response rate in patients with measurable disease, and radiographic progression free survival (rPFS).

The completed Phase 1 trial includes a total of 56 patients from the dose-escalation and dose-expansion cohorts. The efficacy analysis includes patients who received a starting dose of FG-3246 of ≥ 1.2 mg/kg in the dose-escalation cohort, and patients who received 2.7 mg/kg AjBW with a histologic diagnosis of adenocarcinoma in the dose-expansion cohort. Patients were heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246.

In the efficacy analysis, PSA reductions of ≥ 50% were observed in 36% of PSA evaluable patients. For RECIST evaluable patients, 20% met the criteria of a partial response, or tumor reduction in size of ≥ 30%, with a median duration of response of 7.5 months. The median rPFS in this heavily pre-treated patient population was 8.7 months.

The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy.

"The results from the FOR46-001 Phase 1 study are promising, demonstrating a manageable safety profile and continued robust signals of clinical activity," stated Dr. Rahul Aggarwal, Professor of Medicine at University of California San Francisco and Lead Investigator of the study. "The observed median radiographic progression free survival of 8.7 months in patients treated with a starting FG-3246 dose of 1.2 mg/kg and higher is quite favorable and highlights the therapeutic potential of FG-3246 as a new ADC aimed at a novel target. These findings warrant further investigation and hold promise for addressing the therapeutic needs of patients with CD46 positive prostate cancer. We are also excited about potential combinations with FG-3246 and will be presenting investigator sponsored trial data of FG-3246 in combination with enzalutamide at the upcoming ASCO (Free ASCO Whitepaper) 2024 annual meeting."

Earlier data from the FOR46-001 trial had been presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 annual meeting1, and complete results from the study are being submitted to a medical journal for publication in 2024.

About the Phase 1 Study
FOR46-001 (NCT03575819) is a Phase 1, dose-escalation study to evaluate multiple doses of IV-administered FG-3246 (also known as FOR46) in patients with mCRPC who have progressive disease on at least one ARSI, followed by a dose-expansion cohort, to evaluate the safety, tolerability, PK, biological activity, and preliminary evidence of anti-tumor activity of FG-3246 in this patient population.

Thirty-three (33) patients were enrolled in the dose-escalation phase of the study at doses between 0.1 mg/kg and 3.0 mg/kg every three weeks (Q3W), with adjusted body weight dosing (AjBW) used at most dose levels above 2.1 mg/kg. Safety and tolerability of FG-3246 were evaluated in the dose-escalation period of the study.

Twenty-three (23) patients were enrolled in the dose-expansion period of the study; 18 patients with adenocarcinoma mCRPC (Cohort 1) and five patients with neuroendocrine prostate cancer (Cohort 2). All patients in the expansion cohorts were treated at 2.7 mg/kg AjBW to a maximum of 270 mg every three weeks.

The safety profile of FG-3246 was characterized, and anti-tumor activity of FG-3246 in adenocarcinoma patients dosed at ≥ 1.2 mg/kg was evaluated.

About Metastatic Castration-Resistant Prostate Cancer
Prostate cancer develops when malignant cells form and grow in the prostate gland. Prostate cancer is the most common cancer in men in the United States, who currently have a 1 in 8 lifetime risk of developing the disease.2 Approximately 290,000 new diagnoses of prostate cancer and nearly 35,000 deaths were estimated in the U.S. in 2023.2 Metastatic castration-resistant prostate cancer (mCRPC) is a form of advanced prostate cancer that shows signs of growth, even with low levels of testosterone.2 With mCRPC, the cancer stops responding to hormone therapies and can be life-threatening if it spreads to other parts of the body such as nearby lymph nodes, bones, the bladder, rectum, liver, lungs, and the brain. Death from prostate cancer is typically the result of mCRPC, with a 5-year survival rate of 34%3, and the unfortunate reality remains that mCRPC is an incurable disease.4

About FG-3246
FG-3246 (also known as FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types, and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1/2 study being conducted at UCSF to evaluate it in combination with enzalutamide with initial data expected in mid-2024, and a biomarker trial using a PET biomarker for CD46 using the same antibody backbone. We anticipate the initiation of the Phase 2 trial in metastatic castration-resistant prostate cancer in the second half of 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.

On April 2, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company has completed the rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for the HER2-targeted bispecific antibody zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) (Press release, Jazz Pharmaceuticals, APR 2, 2024, View Source [SID1234641719]). If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S.

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"This important milestone brings us one step closer to delivering zanidatamab, a targeted treatment option, to patients living with HER2-positive BTC, a type of cancer that is associated with a five-year overall survival rate of less than 5%," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Zanidatamab is a biparatopic HER2-targeted bispecific antibody that simultaneously binds two non-overlapping epitopes of HER2 resulting in multiple mechanisms of action. Second-line (2L) BTC represents the first of multiple indications we are evaluating and we are excited about zanidatamab’s potential as a new option for multiple HER2-expressing cancers, with ongoing Phase 3 trials in 1L BTC, 1L gastroesophageal adenocarcinoma (GEA), and previously treated breast cancer."

The BLA includes data from the Phase 2b HERIZON-BTC-01 trial of zanidatamab in previously treated HER2-positive BTC. The primary endpoint was confirmed objective response rate (cORR) by independent central review (ICR) in Cohort 1. Data as of Oct. 10, 2022, from the 80 HER2-positive BTC patients enrolled in Cohort 1 of the trial demonstrated a cORR of 41.3% [95% confidence interval (CI): 30.4, 52.8] with a Kaplan Meier (KM) estimated median duration of response (DOR) of 12.9 months [95% CI: 6.0-not estimable] by ICR. Historical response rates for 2L standard-of-care chemotherapy in patients with BTC are reported to be 5 to 15%1,2. The KM estimated median progression-free survival (PFS) was 5.5 months [95% CI: 3.7, 7.2] with a range of 0.3 to 18.5 months.

Zanidatamab demonstrated a manageable and tolerable safety profile, with only two patients (2.3%) in HERIZON-BTC-01 experiencing adverse events (AEs) leading to treatment discontinuation. There were no Grade 4 AEs, and no deaths were considered treatment-related. The most common AEs were diarrhea and infusion-related reactions, which were predominately low-grade, reversible and manageable prophylactically with routine supportive care.

These data were featured as an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023, published in The Lancet Oncology, and included in the 2023 Best of ASCO (Free ASCO Whitepaper) program. Quality-of-life data from this trial were also presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 and at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.

The HERIZON-BTC-302 Phase 3 trial (NCT06282575) of zanidatamab in 1L advanced or metastatic HER2-positive BTC was recently initiated and is open for enrollment. The global, open-label, randomized trial will evaluate the efficacy and safety of zanidatamab in combination with standard-of-care therapy against standard-of-care therapy alone. The primary objective of the study is to compare the efficacy of zanidatamab and chemotherapy (cisplatin plus gemcitabine) with or without the addition of a programmed death protein 1/ligand 1 (PD-1/L-1) inhibitor versus chemotherapy with or without a PD-1/L1 inhibitor in patients. HERIZON-BTC-302 is proposed as the confirmatory trial for zanidatamab in BTC.

About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Biliary Tract Cancer
Biliary tract cancer (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers and are often associated with a poor prognosis3,4. The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with BTC annually5,6,7,8 and most patients (> 65%) are diagnosed with tumors that cannot be removed surgically.