On May 31, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines, reported updated overall survival (OS) results from its Phase 1/2 study evaluating GRANITE, an individualized vaccine-based immunotherapy, to treat advanced solid tumors (Press release, Gritstone Oncology, MAY 31, 2022, View Source [SID1234615261]). Additionally, the company announced it is presenting a "Trial in Progress" poster summarizing the Phase 2/3 GRANITE-CRC-1L- study (randomized study for first-line maintenance treatment of metastatic, microsatellite stable colorectal cancer) at the 2022 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"The updated OS data from our Phase 1/2 study continue to demonstrate a correlation between molecular response and overall survival, and points to the potentially significant impact GRANITE is having on lives of patients with advanced stage cancer," said Andrew Allen, M.D., Ph.D., Co-founder, President and Chief Executive Officer of Gritstone. "The median overall survival observed in multiple trials of various therapies in the third-line MSS-CRC setting has been around 6-7 months, which is consistent with what we observed in our study in patients who did not have molecular response (median overall survival of 7.8 months). The very different outcome observed in the molecular responder subset, with median overall survival of over 18 months, is all the more striking given how rarely long-term survival is observed in MSS-CRC patients who have been treated with and progressed on two prior therapies. These maturing data, demonstrating long-term clinical benefit, further support moving GRANITE upstream in the treatment of patients with this grim cancer in the ongoing randomized Phase 2/3 study, which has registrational intent."

The Phase 1/2 study is evaluating the safety, immunogenicity, and clinical activity of GRANITE in combination with PD-1 checkpoint inhibitor, Opdivo (nivolumab) and subcutaneous anti-CTLA-4 antibody, Yervoy (ipilimumab) in advanced solid tumors. This study enrolled and treated 26 patients as of ESMO (Free ESMO Whitepaper) 2021 presentation with previously treated, metastatic solid tumors including patients with colorectal cancer, gastroesophageal adenocarcinoma, and non-small cell lung cancer. As presented at ESMO (Free ESMO Whitepaper) 2021, of 9 patients with MSS-CRC who were treated and evaluable for molecular response, 4 experienced a molecular response (as evidenced by a reduction in circulating tumor DNA [ctDNA]) and continue to have an OS advantage compared to those patients who did not have a molecular response.

Opdivo and Yervoy are trademarks of Bristol-Myers Squibb Company.

Updated overall survival data from GRANITE Phase 1/2:

4 of 9 treated patients with MSS-CRC had a molecular response (as reported during the ESMO (Free ESMO Whitepaper) 2021 data presentation) and the observed median overall survival in this group will now exceed 18 months (median OS not yet reached versus 7.8 months in those who did not have a molecular response).
All patients with MSS-CRC assessed for molecular response and alive at the time of the ESMO (Free ESMO Whitepaper) 2021 data presentation remain alive after an additional 35 weeks of follow-up.
ASCO presentation details are as follows:

Abstract TPS3635: Phase 2/3, randomized, open-label study of an individualized neoantigen vaccine (self-amplifying mRNA and adenoviral vectors) plus immune checkpoint blockade as maintenance for patients with newly diagnosed metastatic colorectal cancer (GRANITE)
Date/Time: Saturday 04 June 2022, 8:00am CST
Session: Gastrointestinal Cancer – Colorectal and Anal
Location: Poster 425b

On May 31, 2022 Fresenius reported that PEMEtrexed for injection, a drug used to treat adult patients with lung cancer and malignant pleural mesothelioma, is now available from Fresenius Kabi in the United States (Press release, Fresenius, MAY 31, 2022, View Source [SID1234615260]). This is the newest addition to the company’s portfolio of generic IV oncology products – the largest such portfolio in the U.S.

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On May 31, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported that members of the company’s management team will participate in fireside chats at the following investor conferences in June (Press release, Exelixis, MAY 31, 2022, View Source [SID1234615258]):

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William Blair 42nd Annual Growth Stock Conference: Exelixis is scheduled to present at 11:00 a.m. ET / 10:00 a.m. CT / 8:00 a.m. PT on Tuesday, June 7, 2022, in Chicago.
2022 Jefferies Healthcare Conference: Exelixis is scheduled to present at 1:30 p.m. ET / 10:30 a.m. PT on Wednesday, June 8, 2022, in New York.
To access the webcast links, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentations to ensure adequate time for any software download that may be required to listen to the webcasts. Replays will also be available at the same location for at least 30 days.

On May 31, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported new preclinical data from an ovarian cancer study conducted in collaboration with Yale Cancer Center (Press release, Enlivex Therapeutics, MAY 31, 2022, View Source [SID1234615257]). The study showed substantial and statistically significant improvements in survival benefit, survival duration and tumor burden reduction when Allocetra was combined with an anti-PD1 checkpoint inhibitor. The data will be featured in an upcoming poster presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the McCormick Place convention center in Chicago, Illinois (United States) from June 3 – 7, 2022.

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The upcoming ASCO (Free ASCO Whitepaper) poster will also highlight a prior preclinical study in mesothelioma cancer that showed a substantial survival benefit when Allocetra was combined with a commercially approved anti-CTLA4 checkpoint inhibitor. Previously reported preclinical data in peritoneal cancer that show a substantial survival benefit when Allocetra is combined with chimeric antigen receptor (CAR) T-cell therapy will also be presented.

Marcus Bosenberg, MD, PhD, Professor of Dermatology, Pathology, and Immunobiology and Director of the Center for Precision Cancer Modeling at Yale Cancer Center, commented: "I am highly encouraged by these preclinical findings, which clearly demonstrate Allocetra’s potential to address a long-standing unmet need. The immunosuppressive microenvironments of ovarian tumors have limited the clinical benefits of checkpoint inhibition in this indication. Allocetra may reverse immunosuppressive tumor microenvironments and may ultimately improve patient outcomes by synergistically enhancing checkpoint inhibitor efficacy in clinical trials."

Prof. Dror Mevorach, MD, Chief Scientific Officer of Enlivex, added: "In these latest murine studies, we once again saw Allocetra synergistically combine with a checkpoint inhibitor to deliver a statistically significant survival benefit in a difficult-to-treat solid tumor model. We are now working to translate these promising findings to the clinic and expect to initiate two solid tumor trials evaluating Allocetra-based combinations by year-end. Through these studies, we aim to clinically demonstrate the broad applicability of Allocetra’s proposed mechanism of action to enable the expansion of its potential therapeutic impact."

Ovarian Cancer, Checkpoint Inhibitors, and Macrophage-Solid Tumor Dynamics

Ovarian cancer is currently the fifth leading cause of cancer death among women. Stand-alone therapy with PD1 checkpoint inhibitors, which are designed to treat cancer by activating immune cells that can identify and destroy tumors, has thus far shown limited efficacy in this indication. Prior clinical trials in ovarian cancer evaluating anti-PD1 monotherapy have shown response rates of only 7% – 15%.

The limited response rates of checkpoint inhibitors in ovarian and other solid cancers is linked to tumor defense mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. Pro-tumor TAMs typically form a physical layer on top of solid tumors and induce an immunosuppressive tumor microenvironment (TME). This in-turn promotes tumor growth and metastasis and makes it very difficult for immune cells or any anti-cancer drug to efficiently attack cancerous cells. Allocetra is a cell therapy in development that is targeted towards TAMs. Its proposed mechanism of action is to change the balance of macrophage populations so that they skew towards anti-tumor macrophages and away from pro-tumor macrophages. This is expected to enhance the efficacy of checkpoint inhibitors and other immunotherapeutic agents.

The Ovarian Cancer Model

To expand upon its previous preclinical findings in mesothelioma and test the potential effects of cell-therapy-induced macrophage reprogramming in a second difficult-to-treat solid tumor model, Enlivex collaborated with the Yale Cancer Center to run preclinical studies in which groups of mice were implanted with ID8 ovarian cancer cells. The difference between the groups was the treatment given, which started on day 7 after the cancer’s initial growth period.

Results from the preclinical ovarian cancer study further support Allocetra’s potential to significantly improve survival outcomes by facilitating macrophage reprogramming in the solid tumor microenvironment. Twelve weeks after the initial treatment, untreated mice (vehicle) showed a survival rate of 0%, and a median survival duration of 6 weeks. Survival duration was increased with stand-alone treatment with either an anti-PD1 inhibitor or Allocetra. The magnitude of the increases were similar between these two monotherapy groups (42% and 58% increase, respectively), with no significant effect on overall survival probability observed between the monotherapy groups. Notably, combining Allocetra with anti-PD1 therapy led to a synergistic anti-cancer effect, with survival rates of up to 50% (5/10) and an 83% increase in median survival duration observed in the combination therapy groups. The attached figure shows the Kaplan-Meier survival probability curve for each group of the study, and the table below provides the treatment data.

As previously reported, Enlivex plans to initiate a Phase Ib trial evaluating Allocetra in combination with chemotherapy in solid peritoneal tumors in Q3 2022, and a Phase I/II trial evaluating Allocetra in combination with an immune checkpoint inhibitor in late 2022.

The title of the upcoming ASCO (Free ASCO Whitepaper) poster is "In-vivo reprogramming macrophages and dendritic cells with Allocetra-OTS: Successful mono- and combination-antitumor therapy." The poster will be presented during the ASCO (Free ASCO Whitepaper) Annual Meeting’s "Developmental Therapeutics – Immunotherapy" poster session, which is taking place on June 5, 2022, from 8:00 AM – 11:00 AM CDT (9:00 AM – 12:00 PM ET). A copy of the poster’s corresponding abstract is currently available on the ASCO (Free ASCO Whitepaper) Annual Meeting Website.

ABOUT THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY

Founded in 1964, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) is the world’s leading professional organization for physicians and oncology professionals caring for people with cancer.

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On May 31, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that it will host an Innovation Day focused on early research and development on Tuesday, June 21, 2022 at 2:00 PM ET (Press release, CRISPR Therapeutics, MAY 31, 2022, View Source [SID1234615254]).

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CRISPR Therapeutics’ Innovation Day will focus on the Company’s differentiated genetic engineering platform technologies, novel approach to cell and gene therapy, and emerging discovery programs.

A live webcast of the event will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 30 days following the presentation. Please contact [email protected] for any questions regarding the event.