On April 26, 2023 Verastem Oncology, (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that an abstract highlighting updated interim results from Part A of the ongoing Phase 2, registration-directed RAMP 201 trial evaluating avutometinib (VS-6766) and defactinib in patients with low-grade serous ovarian cancer (LGSOC) has been selected for a presentation in a Poster Discussion Session at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2–6, 2023 in Chicago, IL (Press release, Verastem, APR 26, 2023, View Source [SID1234630559]).

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The objective of Part A (selection Phase) of the RAMP201 LGSOC study was to determine the go forward regimen between avutometinib monotherapy or the combination of avutometinib and defactinib to be studied in Part B (expansion Phase) of the study. The efficacy and safety of each regimen were assessed in both KRAS mutant and KRAS wild-type recurrent LGSOC. The ongoing expansion Phase of the trial, which is fully enrolled, will evaluate the efficacy and safety of the regimen selected.

"Building on our breakthrough therapy designation, we are pleased with the continued progress of our LGSOC program and look forward to the presentation of these updated results from the RAMP 201 trial at ASCO (Free ASCO Whitepaper) 2023," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "LGSOC is a difficult disease to treat and one in need of improved therapies to address this unique ovarian cancer. We are working to bring forward what may be the first therapy specifically approved for patients with LGSOC as quickly as possible."

The Company is in ongoing discussions with the U.S. Food and Drug Administration (FDA) on confirmatory study plans and intends to provide an update after agreement with the FDA. Continued enrollment in the combination arm of RAMP 201 is planned to expand the clinical experience in anticipation of initiation of a confirmatory study.

Details for the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting presentation are as follows:

Title: Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC).
Lead author: Susana Banerjee, Institute of Cancer Research and The Royal Marsden
Abstract #: 5515
Session: Gynecologic Cancer
Poster Session Display Date and Time: 6/5/2023, 1:15 PM-4:15 PM
Poster Discussion Session Date and Time: 6/5/2023, 4:30 PM-6:00 PM
Poster Board Number: 210

About Low-Grade Serous Ovarian Cancer (LGSOC)

Low-grade serous ovarian cancer (LGSOC) is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 30% of cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.

About Avutometinib (VS-6766)

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to other MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS- driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. As part of the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, Verastem Oncology is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

On April 26, 2023 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported clinical data from the Phase 1 dose escalation study of PRGN-3005 UltraCAR-T in patients with advanced, recurrent platinum resistant ovarian cancer, and the Phase I study of PRGN-2009 AdenoVerse immunotherapy alone or in combination with an anti-PDL1/TGF-Beta trap checkpoint inhibitor in patients with HPV-associated cancers will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place from June 2-6, 2023 at McCormick Place in Chicago, Illinois (Press release, Precigen, APR 26, 2023, View Source [SID1234630558]).

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Abstract Title Abstract # Presentation Details

Phase I evaluation of PRGN-2009 alone and in combination with
bintrafusp alfa in patients (pts) with recurrent/metastatic (R/M) HPV-
associated cancers (HPV-C)

2628

Session Title:
Developmental Therapeutics—
Immunotherapy

Session Date and Time:
June 3, 2023
8:00 AM-11:00 AM CT

Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells
manufactured overnight for infusion next day to advanced stage platinum
resistant ovarian cancer patients

5590

Session Title
Gynecologic Cancer

Session Date and Time:
June 5, 2023
1:15 PM-4:15 PM CT

Event details are available on Precigen’s website in the Events & Presentations section at investors.precigen.com/events-presentations.

Precigen: Advancing Medicine with Precision
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on Twitter @Precigen, LinkedIn or YouTube.

UltraCAR-T
UltraCAR-T is a multigenic autologous CAR-T platform that utilizes Precigen’s advanced non-viral Sleeping Beauty system to simultaneously express an antigen-specific CAR to specifically target tumor cells, mbIL15 for enhanced in vivo expansion and persistence, and a kill switch to conditionally eliminate CAR-T cells for a potentially improved safety profile. Precigen has advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating a novel mechanism for intrinsic checkpoint blockade without the need for complex and expensive gene editing techniques. UltraCAR-T investigational therapies are manufactured via Precigen’s overnight manufacturing process using the proprietary UltraPorator electroporation system at the medical center and administered to patients only one day following gene transfer. The overnight UltraCAR-T manufacturing process does not use viral vectors and does not require ex vivo activation and expansion of T cells, potentially addressing major limitations of current T cell therapies.

UltraCAR-T Clinical Program
The UltraCAR-T platform has shifted the autologous CAR-T manufacturing paradigm using an advanced non-viral multigene delivery system and an overnight, decentralized manufacturing process for administration of autologous CAR-T cells one day after gene transfer to reduce vein-to-vein time for autologous CAR-T treatment. Precigen’s UltraCAR-T platform is currently under clinical investigation for hematological and solid tumors, including a Phase 1/1b study of PRGN-3005 UltraCAR-T in patients with advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer (NCT03907527), a Phase 1/1b study of PRGN-3006 UltraCAR-T in patients with relapsed or refractory acute myeloid leukemia (AML) or higher risk myelodysplastic syndrome (MDS) (NCT03927261) and a Phase 1/1b study of PRGN-3007 UltraCAR-T incorporating PD-1 checkpoint inhibition in patients with ROR1-positive (ROR1+) hematologic chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and solid tumor triple negative breast cancer (TNBC) malignancies (NCT05694364). PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation and Fast Track Designation in patients with AML by the US Food and Drug Administration (FDA).

UltraPorator

The UltraPorator system is an exclusive device and proprietary software solution for the scale-up of rapid and cost-effective manufacturing of UltraCAR-T therapies and potentially represents a major advancement over current electroporation devices by significantly reducing the processing time and contamination risk. The UltraPorator device is a high-throughput, semi-closed electroporation system for modifying T cells using Precigen’s proprietary non-viral gene transfer technology. UltraPorator is being utilized for clinical manufacturing of Precigen’s investigational UltraCAR-T therapies in compliance with current good manufacturing practices.

AdenoVerse Immunotherapy
Precigen’s AdenoVerse immunotherapy platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. Precigen’s gorilla adenovectors, part of the AdenoVerse library, have potentially superior performance characteristics as compared to current competition. AdenoVerse immunotherapies have been shown to generate high-level and durable antigen-specific neutralizing antibodies and effector T cell immune responses as well as an ability to boost these antibody and T cell responses via repeat administration. Superior performance characteristics and high yield manufacturing of AdenoVerse vectors combined with UltraVector technology allows Precigen to engineer cutting-edge investigational gene therapies to treat complex diseases.

AdenoVerse Immunotherapy Clinical Program
Precigen’s AdenoVerse Immunotherapy platform is currently under clinical investigation in a Phase 1/2 study of PRGN-2009 AdenoVerse immunotherapy alone or in combination with anti-PDL1/TGF-Beta Trap (M7824) in patients with HPV-associated cancers (NCT04432597) and a Phase 2 study of PRGN-2012 AdenoVerse immunotherapy in patients with recurrent respiratory papillomatosis (NCT04724980). PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the FDA.

Trademarks
Precigen, UltraCAR-T, UltraPorator, UltraVector, AdenoVerse, and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking Statements
Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company’s current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company’s business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company’s portfolio of therapies, and in particular its CAR-T and AdenoVerse therapies. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company’s clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company’s most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

On April 26, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported that the Journal of Clinical Oncology published in a Rapid Communication data indicating adagrasib, a potent and selective KRASG12C inhibitor, is well tolerated and demonstrates meaningful clinical activity in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and other solid tumors harboring a KRASG12C mutation (Press release, Mirati, APR 26, 2023, View Source [SID1234630557]). Rapid Communications are reserved for publications deemed to represent timely and late breaking research that may have an immediate impact on patient care.

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In addition, findings were presented last week at the April session of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series Program. This publication follows the recent inclusion of KRAZATI(adagrasib) in the National Comprehensive Center Network (NCCN) Guidelines for Central Nervous System (CNS) Cancers for patients living with previously treated KRASG12C-mutant non-small cell lung cancer (NSCLC) and CNS metastases.

The Phase 2 data of the KRYSTAL-1 study demonstrates the potential of adagrasib as a monotherapy in patients with unresectable or metastatic KRASG12C-mutated solid tumors beyond NSCLC and colorectal cancer (CRC). The data presented was based on confirmed blinded, independent, central review (BICR) responses. This is the largest Phase 2 dataset evaluating KRAS G12C mutated solid tumors other than non-small cell lung cancer and colorectal cancer.

The enrolled and treated population (n=63) included 21 PDAC, 12 BTC, 9 appendiceal adenocarcinoma, 4 gastroesophageal/esophageal adenocarcinoma, 3 small bowel adenocarcinoma, 5 ovarian adenocarcinoma, 4 unknown primary, 3 endometrial adenocarcinoma, 1 breast adenocarcinoma and 1 glioblastoma. The median prior lines of systemic therapy was two. Results showed an objective response rate (ORR) of 35% for the overall cohort. In patients with PDAC, ORR was 33%; for patients with BTC, ORR was 42%. Notably, findings demonstrate the safety profile of adagrasib is aligned with previously reported data in patients with pretreated NSCLC and CRC.

These findings demonstrate a meaningful improvement relative to the historically reported standard of care for PDAC and BTC. For patients with previously treated metastatic PDAC, current standard of care (gemcitabine + nab-paclitaxel or liposomal irinotecan + 5FU/leucovorin) has resulted in limited ORR (3-16%).1-2 In a biomarker-unselected BTC patient population, the ABC-06 phase 3 trial investigating FOLFOX in the second-line setting reported an ORR of 5%.3

"We are thrilled to see the results of this Phase 2 study, which demonstrate a marked improvement on the current standard of care for patients with unresectable or metastatic KRASG12C-mutated solid tumors, including PDAC, BTC, other gastrointestinal (GI) and non-GI tumors, where few treatment options exist. It is particularly encouraging to see meaningful clinical activity in pancreatic and biliary tract cancers tumors," said Shubham Pant, M.D., M.B.B.S., The University of Texas MD Anderson Cancer Center. "The data indicates that adagrasib has the potential to be an effective treatment for KRASG12C-mutated solid tumor types in addition to NSCLC and CRC."

"We’re pleased to share this data which demonstrates meaningful clinical activity in KRASG12C-mutated tumor types in addition to NSCLC and CRC, indicating a potential path to regulatory approval for adagrasib in additional indications," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We look forward to continuing to advance adagrasib as a potential best-in-class treatment option for patients harboring a KRASG12C mutation."

The primary endpoint for the Phase 2 cohort of the KRYSTAL-1 study was objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival and safety.

Findings were presented last week at the April session ASCO (Free ASCO Whitepaper) Plenary Series Program as a data presentation (Abstract 425082) titled, "KRYSTAL-1: Activity and Safety Of Adagrasib (MRTX849) In Patients With Advanced Solid Tumors Harboring A KRASG12C Mutation." The full abstract for the presentation can be found here: Program Guide – ASCO (Free ASCO Whitepaper) Meeting Program Guide.

The full Journal of Clinical Oncology article can be found here.

About KRAZATI (adagrasib)

In the U.S., KRAZATI was approved by the FDA for Accelerated Approval (Subpart H), which allows for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Mirati submitted a Marketing Authorization Application (MAA) in the EU in May 2022. In 2021, adagrasib achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. For Prescribing Information, visit Mirati.com/KRAZATI_USPI

Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.

KRAZATI (adagrasib) U.S. Indication

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

On April 26, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of a paper in Molecular Therapy Nucleic Acids1, titled ‘Novel Fas-TNFR chimeras that prevent Fas ligand-mediated kill and signal synergistically to enhance CAR T-cell efficacy (Press release, Autolus, APR 26, 2023, View Source [SID1234630556]).’

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CAR T cells have shown remarkable efficacy against hematological cancers, but their effectiveness in solid tumors has been limited by inhibitory factors expressed by the tumor or its microenvironment. One such inhibitory factor is Fas ligand (FasL), which binds to the Fas receptor (CD95) on the surface of an activated T cell and triggers the CAR T cell to die by apoptosis.

The research group at Autolus tested several Fas chimeras which consist of the extracellular domain of Fas fused to the intracellular domain from different TNF receptor superfamily members. Expression of these chimeras in a CAR T cell not only blocks apoptosis triggered by FasL, but results in co-stimulation, which promotes CAR T cell survival and proliferation.

A small subset of these chimeras, best exemplified by Fas-CD40 fusion, were found to be particularly effective at promoting CAR T cell survival and anti-tumor cytotoxicity in the presence of FasL. These data support the potential of this Fas-CD40 chimera to render T cell therapies resistant to FasL-mediated cell death and improve their effectiveness against solid tumors.

Martin Pule, Chief Scientific Officer and Founder of Autolus said, "Development of Fas-CD40 adds to our growing toolkit of T-cell engineering modules and aligns with Autolus’ strategy for increasing the Company’s capabilities, with particular application against complex and immunologically hostile cancers, including solid cancer applications."

1. Novel Fas-TNFR chimeras that prevent Fas ligand-mediated kill and signal synergistically to enhance CAR T-cell efficacy

On April 26, 2023 NexImmune, Inc. (Nasdaq: NEXI), a biotechnology company developing a novel approach to immunotherapy designed to orchestrate a targeted immune response by directing the function of antigen-specific T cells for liquid and solid malignancies, reported that clinical data from its Phase 1/2 dose escalation study of NEXI-001 will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting in Chicago, June 2 – June 6, 2023 (Press release, NexImmune, APR 26, 2023, View Source [SID1234630555]).

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Poster Presentation:

Title: An Analysis of a First-In-Human Study of NEXI-001 Donor-Derived Antigen-Specific CD8+ T-Cell Treatment of Relapsed AML after Allogeneic Hematopoietic Cell Transplantation (HCT)

Abstract #: 7043 (Poster Board #173)

Session Title: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant

Authors: Monzr M. Al Malki, MD1, Juan C. Varela MD, PhD2, Sumithira Vasu, MBBS3, Dipenkumar Modi, MD4, Suzanne Afonso-Smith, PhD5, Sojung Kim, PhD5, Emily Lu, PhD5, Robert D. Knight, MD5, and Mathias Oelke, PhD5

(1)Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, (2)Advent Health Blood and Marrow Transplant Program, Orlando, FL, (3)Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus Ohio, (4)Division of Oncology, Karmanos Cancer Center/Wayne State University, Detroit, MI, (5)NexImmune, Inc., Gaithersburg, MD