On August 8, 2022 Compugen Ltd. (NASDAQ: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that the European Patent Office has granted Compugen a new patent covering anti-PVRIG antibodies for use in cancer treatment (Press release, Compugen, AUG 8, 2022, View Source [SID1234617823]).

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European Patent No. 3 653 221 link titled "Anti-PVRIG antibodies and Methods of Use" augments previously issued patents by expanding and protecting the use of COM701 for treating cancer patients, to include any anti-PVRIG antibody for use in the treatment of cancer, wherein the antibody activates T cells and/or NK cells and competes with COM701 for specific binding to PVRIG. The patent further claims such anti-PVRIG antibodies for use in the treatment of cancer, wherein the anti-PVRIG antibody is used in combination with antagonistic antibodies targeting additional immune checkpoints.

"As part of our strategy to secure broad patent protection for our innovative portfolio, we are delighted to be granted protection against any antibody that competes with our potentially first-in- class anti-PVRIG, COM701, and activates T or/and NK cells for treatment of cancer," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen.

European Patent No. 3 653 221 link is expected to expire no earlier than February 2036.

About COM701
COM701 is a humanized antibody that binds with high affinity to PVRIG, a novel immune checkpoint discovered computationally by Compugen, blocking the interaction with its ligand, PVRL2. In pre-clinical studies, blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. Compugen has identified PVRIG and TIGIT as key parallel and complementary inhibitory pathways in the DNAM-1 axis, which also intersect with the well-established PD-1 pathway. Research from Compugen suggests that these three pathways have different dominance in different tumor types and patients, implying that to induce effective antitumor responses, certain patient populations may require the blockade of different combinations of these three pathways. To test this hypothesis, Compugen has established a science-driven, biomarker informed clinical program, which evaluates different combinations of these axis members across tumor types. Compugen is the only company with clinical assets targeting both PVRIG and TIGIT in its portfolio allowing it to explore the potential of blocking these parallel and complementary members of the DNAM axis comprehensively to drive robust immune responses.

MacroGenics has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On August 7, 2022 ImmVira reported that it’s brand new oncolytic herpes simplex virus ("oHSV") product MVR-C5252 targeting Malignant Glioma has obtained Orphan Drug Designation ("ODD") from U.S. Food and Drug Administration ("FDA") (Press release, Immvira, AUG 7, 2022, View Source [SID1234617721]).

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Malignant glioma has been a special challenge for patients and healthcare professionals for a long time, with limited treatment options including surgical resection, chemotherapy, and/or radiation therapy. The prognosis for the disease also remains poor, with median overall survival ("OS") varying between 12 – 14 months, a 5-year survival ranging from 4% to 5% and a nearly 100% relapse rate, representing a huge unmet medical need.

Developed on ImmVira’s OvPENS new drug development platform, MVR-C5252 is designed specifically for the treatment of glioma by specific attenuation to achieve on-target malignant gliocyte killing while maintaining safety profile. MVR-C5252 is also the only oncolytic virus product targeting brain tumors that carries specific exogenous genes to promote the immune response of tumor microenvironment and achieve optimal anti-tumor activity. MVR-C5252 has obtained IND clearance from the U.S. FDA and is currently under preparation for Phase I clinical study.

FDA enacted the Orphan Drug Act to encourage and provide special incentives to pharmaceutical companies that undertake the responsibility of developing orphan drugs that target diseases affecting fewer than 200,000 people in the United States. The ODD status will further accelerate the clinical development and registration of MVR-C5252 in the United States, and will also allow MVR-C5252 to enjoy exclusive marketing and development rights and other benefits, such as protocol assistance from FDA, potential decreased wait-time for drug approval, discounts on certain fees, and eligibility for seven years of market exclusivity in the United States, etc.

Dr. Grace Guoying Zhou, ImmVira’s Chairwoman and CEO, said, "ODD status granted by FDA to MVR-C5252 means a lot for glioma patients, and also demonstrated FDA’s recognition for this product and company’s clinical development and registration capability as well. ImmVira will continue to advance the clinical development of MVR-C5252 in both U.S. and China, promote the early launch of the candidate product to save more patients’ lives."

On August 7, 2022 Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") reported the completion of first patient dosing in the U.S. Phase I clinical trial of ASC61, an oral PD-L1 small molecule inhibitor prodrug, for treatment of advanced solid tumors (Press release, Ascletis, AUG 7, 2022, View Source [SID1234617722]).

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This U.S. Phase I trial is a dose-escalation study to evaluate the safety and tolerability of ASC61 as well as to define the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ASC61 in patients with advanced solid tumors who have disease progression during or following standard therapy.

ASC61 is an oral small molecule inhibitor prodrug. Its active metabolite, ASC61-A, is a potent and highly selective inhibitor which blocks PD-1/PD-L1 interaction through inducing PD-L1 dimerization and internalization. As a single agent, ASC61 demonstrated significant antitumor efficacy in multiple animal models including humanized mouse model. Preclinical studies showed that ASC61 has good safety and pharmacokinetic profiles in animal models. ASC61 oral tablets used in the clinical trial, were developed with the in-house proprietary technology of Ascletis.

In a head-to-head comparison study using the human PD-L1 expressing cells and fresh peripheral blood mononuclear cells (PBMCs) co-culture assay, ASC61-A treatment induced secretion of IFNγ in a concentration dependent manner, with an EC50 of 2.86 nM. Maximal levels of IFNγ induced by ASC61-A were similar to that induced by Keytruda.

Compared with PD-1/PD-L1 antibody injections, the oral PD-L1 inhibitor ASC61 has the following benefits: (1) higher patient compliance with easy and safe administration with no need of hospital visits for injections; (2) ease of all oral combination therapies with other oral anti-tumor drugs; (3) easier to manage immune-related adverse effects (irAEs) with dose adjustment; (4) relatively lower cost; and (5) higher permeability to distribute into targeted tissues.

"Immunogenicity and the poor permeability of tumor tissues are the major disadvantages of therapeutic antibodies, which can cause a low response rate of PD-1/PD-L1 antibodies. As a highly differentiated small molecule PD-L1 inhibitor, ASC61 has several advantages over antibodies, and showed promising preliminary efficacy and safety profile in preclinical studies. This progress of ASC61 on advanced solid tumors further demonstrated Ascletis’ global R&D capability and execution. We expect to further advance the studies on ASC61 to provide more options for patients with advanced solid tumors." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

On August 7, 2022 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported the presentation of the final progression-free survival (PFS) analysis results from the registrational GEMSTONE-301 study of sugemalimab as a consolidation therapy in patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease had not progressed after concurrent or sequential chemoradiotherapy at the IASLC 2022 World Conference on Lung Cancer (WCLC) (Press release, CStone Pharmaceauticals, AUG 7, 2022, View Source [SID1234617723]). The data showed sugemalimab maintained a statistically significant and clinically meaningful improvement in the PFS as assessed by blinded independent central review (BICR). Subgroup analysis demonstrated clinical benefits in patients who had received either concurrent or sequential chemoradiotherapy prior to sugemalimab.

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The GEMSTONE-301 study is a multicenter, randomized, double-blind phase 3 clinical trial, designed to evaluate the efficacy and safety of sugemalimab as a consolidation therapy in patients with unresectable stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy. In May 2021, the GEMSTONE-301 study met its primary endpoint at pre-planned interim analysis. The findings showed that sugemalimab demonstrated a statistically significant and clinically meaningful improvement in PFS as compared to placebo. Subgroup analyses demonstrated that sugemalimab was associated with clinical benefits regardless of whether patients received concurrent or sequential chemoradiotherapy prior to sugemalimab.

The results presented at the WCLC 2022 were based on the PFS final analysis data. As of March 1, 2022, key results of this study are the following:

BICR-assessed median PFS: 10.5 months for sugemalimab vs 6.2 months for placebo (HR= 0.65, 95% CI 0.50–0.84)
– For patients who received sequential chemoradiotherapy: the median PFS was 8.1 months vs 4.1 months, HR=0.57

– For patients who received concurrent chemoradiotherapy: the median PFS was 15.7 months vs 8.3 months, HR=0.71

Preliminary overall survival data showed a trend for benefit favoring sugemalimab, median overall survival (OS): not reached for sugemalimab vs 25.9 months for placebo (HR= 0.69, 95% CI 0.49-0.97)
– For patients who received sequential chemoradiotherapy: the median OS was not reached vs 24.1 months, HR=0.60

– For patients who received concurrent chemoradiotherapy: the median OS was not reached vs 32.4 months, HR=0.75

Similar objective response rate (ORR) was seen between sugemalimab and placebo but duration of overall response (DoR) was longer with sugemalimab
– ORR: 24.5% vs 25.2%

– DoR: 24.1 months vs 6.9 months

Sugemalimab had a well-tolerated safety profile; no new safety signals were observed in PFS final analysis
Professor Yi-Long Wu, a tenured director of Guangdong Provincial People’s Hospital, and the Leading Principal Investigator on the GEMSTONE-301 study, said, "The final PFS results from GEMSTONE-301 showed that sugemalimab as a consolidation therapy demonstrated PFS and OS benefits in patients with unresectable stage III NSCLC following concurrent or sequential chemoradiotherapy. The overall benefit was consistent with that in the PACIFIC study. Sugemalimab could be safely and effectively used after concurrent or sequential chemoradiotherapy and become a standard of care in this setting for unresectable stage III NSCLC. Sugemalimab has been approved in China for the treatment of patients with stage III NSCLC and recommended by 2022 Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Primary NSCLC as a preferred treatment option."

Dr. Jason Yang, Chief Medical Officer of CStone, said, "We are delighted that the updated results of GEMSTONE-301 are presented at WCLC 2022 and highlighted in the press conference session. In the final PFS analysis, sugemalimab demonstrated clinical benefits in patients receiving either concurrent or sequential chemoradiotherapy, while preliminary OS benefits were also observed. The interim PFS data has been published in the journal of The Lancet Oncology. We are working with our partner to engage regulatory agencies worldwide and to bring sugemalimab to more cancer patients with its robust efficacy and safety profile."

About the GEMSTONE-301 study

The GEMSTONE-301 study (clinicaltrials.gov registration number: NCT03728556; drug clinical trial registration number: CTR20181429) is a multicenter, randomized, double-blind phase 3 clinical trial, designed to evaluate the efficacy and safety of sugemalimab as consolidation therapy in patients with unresectable stage III NSCLC whose disease had not progressed following concurrent or sequential chemoradiotherapy. The trial’s primary endpoint was PFS as assessed by BICR according to RECIST v1.1; the secondary endpoints included OS, PFS as assessed by investigators and safety.

In May 2021, the GEMSTONE-301 study met its primary endpoint at a pre-planned interim analysis reviewed by the iDMC. The findings showed that sugemalimab demonstrated statistically significant and clinically meaningful improvement in the BICR assessed PFS. Investigator-assessed PFS showed consistent results as those of the primary endpoint. Sugemalimab was well tolerated with no new safety signals. Subgroup analyses demonstrated that sugemalimab was associated with clinical benefit regardless of whether patients received concurrent or sequential chemoradiotherapy prior to sugemalimab. The data were reported in the late-breaking abstract (LBA) presentation at the 2021 ESMO (Free ESMO Whitepaper) Annual Meeting and published in The Lancet Oncology in January 2022.

About Sugemalimab

The anti-PD-L1 monoclonal antibody sugemalimab was developed by CStone using OmniRat transgenic animal platform, which allows creation of fully human antibodies in one step. Sugemalimab is a fully human, full-length anti-PD-L1 immunoglobulin G4 (IgG4) monoclonal antibody, which may allow a reduced the risk of immunogenicity and toxicity for patients, a unique advantage over similar drugs.

Currently, the National Medical Products Administration of China has approved sugemalimab (Cejemly):

In combination with pemetrexed and carboplatin as first-line treatment of patients with metastatic non-squamous NSCLC, lacking EGFR and ALK genomic tumor aberrations; and in combination with paclitaxel and carboplatin as first-line treatment of patients with metastatic squamous NSCLC
For the treatment of patients with unresectable stage III non-small cell lung cancer whose disease had not progressed following concurrent or sequential platinum-based chemoradiotherapy
With its proven therapeutic advantages, sugemalimab is recommended by the 2022 Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of NSCLC, in combination with chemotherapy as the first-line treatment of patients with stage IV non-squamous/squamous NSCLC without driver alterations; or as a consolidation therapy in patients with stage III NSCLC following concurrent or sequential platinum-based chemoradiotherapy.

CStone formed a strategic collaboration agreement with EQRx, under which EQRx licensed the exclusive rights to sugemalimab for development and commercialization outside of Greater China.