On December 4, 2023 Immunitas Therapeutics ("Immunitas"), a clinical stage precision immunotherapy company committed to discovering and developing novel, differentiated therapeutics for patients with cancer, reported the appointment of James Wooldridge, M.D., as Chief Medical Officer (CMO) (Press release, Immunitas Therapeutics, DEC 4, 2023, View Source [SID1234638140]). The company also announced it will present new data supporting continued clinical development of its lead program IMT-009 for solid tumors and hematological malignancies at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2023).

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In the CMO role, Dr. Wooldridge will leverage his extensive oncology therapeutic development experience to support clinical advancement strategy for Immunitas’ pipeline of highly differentiated, antibody-based immuno-oncology assets, including lead candidate IMT-009. Dr. Wooldridge has served as Acting CMO since June 2023 and has been an advisor to the Company since October 2022.

"We are pleased to announce Jim’s appointment as our Chief Medical Officer as we continue progressing toward our goal of providing groundbreaking therapeutic solutions for patients with cancer," said Amanda Wagner, Chief Executive Officer of Immunitas. "Over the past year advising Immunitas he has provided invaluable expertise, drawing from his extensive breadth of experience in immuno-oncology development to support advancement of our evolving pipeline. We are delighted to have him on board as our CMO as we continue clinical development of IMT-009 and progress our portfolio of highly differentiated immuno-oncology biologics."

Dr. Wooldridge has more than 20 years of experience in clinical oncology research and drug development spanning the biotechnology, pharmaceutical, and academic sectors. He previously served as the Chief Medical Officer at Checkmate Pharmaceuticals leading up to the company’s acquisition by Regeneron. Additionally, he held the role of Chief Medical Officer at Aeglea BioTherapeutics, where he oversaw development of enzyme-based treatments for rare genetic diseases and cancer.

"I am excited to continue working with this team to further advance the Immunitas pipeline. Our lead program, IMT-009, targets the CD161/CLEC2D axis and is currently dosing in the clinic with key data expected in 2024. The talented Immunitas team has built on our unique expertise in this area to progress a second compelling program for tumors that have traditionally not responded to immune-therapy, and the company’s approach to target discovery is deeply rooted in human biology," said Dr. Wooldridge. "I’m particularly excited by Immunitas’ strategy to develop novel therapeutics using a biomarker-driven approach early in development, and I greatly look forward to continuing my work with this team to bring new therapies to patients."

The data to be presented at ASH (Free ASH Whitepaper) 2023 further supports the therapeutic potential of IMT-009 in hematological malignancies.

IMT-009 is a monoclonal, Fc silent, fully human Immunoglobulin G1 (IgG1) antibody that binds to CD161 with high affinity, selectively blocking interactions with its ligand CLEC2D. Previously reported preclinical data confirm that blocking CD161 with IMT-009 restores activation of effector functions of both CD161+ T and NK cells, enhancing cytotoxicity toward target tumor cells. IMT-009 is currently being evaluated in a Phase 1/2a clinical trial for use as monotherapy and combination treatment in both solid tumors and heme malignancies (NCT05565417).

"The new data to be shared at ASH (Free ASH Whitepaper) 2023 adds to the growing body of evidence supporting IMT-009’s potential as a differentiated treatment approach for hematologic malignancies, in addition to the strong data we have generated in solid tumors. Together with data presented at SITC (Free SITC Whitepaper) 2023 that demonstrated proof-of-concept for our second program, a myeloid and B cell modulating anti CLEC2D-Toll-like receptor 9 (TLR9) agonist conjugate, these data provide further compelling support for our approach targeting the CLEC2D/CD161 axis as a novel ligand-receptor pathway for immunotherapeutic intervention," said Amanda Wagner, Chief Executive Officer of Immunitas.

Presentation Details for ASH (Free ASH Whitepaper) 2023:
Title: Anti CD161 antibody IMT-009 is a novel immunotherapeutic agent that effectively blocks the inhibitory CLEC2D/CD161 axis in CLEC2D+ B Cell hematological malignancies reinvigorating T and NK cell function leading to anti-tumor benefit
Abstract Number: 2815
Date/Time: Sunday, December 10, 2023, 6:00 – 8:00 pm PT

About IMT-009
IMT-009 is a fully human, Fc-attenuated IgG1 monoclonal antibody that binds to CD161 and blocks its interaction with its ligand, CLEC2D. Preclinical data confirm that CD161 blockade with IMT-009 results in enhanced anti-tumor activity. IMT-009 is under evaluation in a Phase 1/2a clinical trial for use as a monotherapy and combination treatment for solid tumor and hematological malignancies. The Phase 1 study is designed to evaluate the safety, tolerability, pharmacodynamic biomarkers, and preliminary efficacy of IMT-009 as well as identify the Recommended Phase 2 Dose (RP2D). The trial will then transition into Phase 2 with multiple expansion cohorts to assess the safety and efficacy of IMT-009 alone or in combination with another antineoplastic agent.

On December 4, 2023 Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC), who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder) (Press release, Johnson & Johnson, DEC 4, 2023, View Source;johnsons-investigational-tar-200-granted-us-fda-breakthrough-therapy-designation-for-the-treatment-of-high-risk-non-muscle-invasive-bladder-cancer-302005075.html [SID1234638138]). TAR-200 is a novel investigational targeted releasing system designed to provide sustained local release of gemcitabine into the bladder. Today’s BTD marks Johnson & Johnson’s 13th such designation in oncology.

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"TAR-200 represents a novel interventional approach for the treatment of localized bladder cancer where today, unfortunately, options are limited and include antiquated BCG therapy or radical cystectomy," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "This Breakthrough Therapy Designation recognizes TAR-200 as a promising advancement and marks an important step forward in our innovative focus to transform the treatment of bladder cancer."

The BTD is supported by data from SunRISe-1 (NCT04640623), an open-label Phase 2b clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients, who are ineligible for or elected not to undergo radical cystectomy.1 Data from the SunRISe-1 study were featured during the 2023 European Society for Medical Oncology Annual Congress as a late-breaking mini-oral presentation (Abstract #LBA105) and interim results were presented at the 2023 American Urological Association Annual Meeting (Abstract #LBA02-03).

A U.S. FDA BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).2

About SunRISe-1

SunRISe-1 (NCT04640623) is an open-label Phase 2b clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients, who are ineligible for or elected not to undergo radical cystectomy. Participants were randomized to one of three cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3). The primary endpoint is Complete Response rate at any time point. Secondary endpoints include duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023.

About TAR-200

TAR-200 is an investigational targeted releasing system enabling controlled release of gemcitabine into the bladder, sustaining local drug exposure for weeks at a time. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer in SunRISe-2 and SunRISe-4 and NMIBC in SunRISe-1 and SunRISe-3.

About Cetrelimab

Administered intravenously, cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination regimen.

About High-Risk Non-Muscle-Invasive Bladder Cancer

High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer, compared to low- and intermediate risk NMIBC.3,4 HR-NMIBC makes up 15–44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors and CIS. Radical cystectomy is currently recommended for NMIBC patients who are unresponsive to BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unable to undergo radical cystectomy.7 The high rates of recurrence and progression can pose significant morbidity and distress for patients with NMIBC.

On December 4, 2023 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III INAVO120 study of the investigational therapy, inavolisib, in combination with palbociclib (Ibrance) and fulvestrant as a potential first-line treatment option for people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer (Press release, Genentech, DEC 4, 2023, View Source [SID1234638137]). The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful improvement compared to palbociclib and fulvestrant alone. Overall survival data were immature at this time, but a clear positive trend has been observed. Follow-up will continue to the next analysis.

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"These pivotal study results for this inavolisib combination represent a transformative medical advance for people with PIK3CA-mutated HR-positive breast cancer," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "We are excited about the opportunity to expand our portfolio of breast cancer medicines into the HR-positive space and bring this potentially best-in-class new treatment option to patients as quickly as possible."

The inavolisib combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, with no new safety signals observed.

Inavolisib is an oral therapy with high in vitro potency and selectivity for PI3Kα inhibition and the ability to specifically trigger the breakdown of mutant PI3Kα protein. With this unique dual mechanism of action, inavolisib may provide well-tolerated,

durable disease control and potentially improved outcomes for people with HR-positive/HER2-negative, PIK3CA-mutated advanced breast cancer. PIK3CA mutations can lead to mutated PI3Kα protein which contributes to uncontrolled tumor growth, disease progression and resistance to endocrine-based treatment.

Inavolisib is currently being investigated in three Phase III clinical studies in people with PIK3CA-mutated metastatic breast cancer (INAVO120, INAVO121, INAVO122) in various combinations.

About the INAVO120 Study

The INAVO120 study [NCT04191499] is a Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints includes overall survival, objective response rate, and clinical benefit rate.

About Hormone Receptor-Positive Breast Cancer

Hormone receptor (HR)-positive breast cancer is the most prevalent type of all breast cancers. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism for resistance to endocrine therapy and CDK4/6 inhibitors.

On December 4, 2023 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that Bill Newell, Chief Executive Officer, will participate in a virtual fireside chat at the JMP Securities Hematology and Oncology Summit on Wednesday, December 6, 2023 at 2:30 p.m. ET / 11:30 a.m. PT (Press release, Sutro Biopharma, DEC 4, 2023, View Source [SID1234638136]).

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A webcast of the fireside chat will be accessible through the News & Events page of the Investor Relations section of the company’s website at www.sutrobio.com. An archived replay will be available for at least 30 days after the event.

On December 4, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that additional data from the Phase 1b/2 clinical trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC) showed two ongoing confirmed partial responses (PRs) at higher dose levels (Press release, Viracta Therapeutics, DEC 4, 2023, View Source [SID1234638135]). These data were featured in an oral presentation made by A. Dimitrios Colevas, M.D., Professor of Medicine (Oncology) at the Stanford Cancer Institute, during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress being held in Singapore. Nana-val is the company’s all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers.

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"The initial efficacy, safety, and pharmacokinetic data from the first five dose cohorts of the Phase 1b trial in patients with recurrent or metastatic EBV-positive NPC are very encouraging," said Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta. "These results support the continued advancement and dose escalation of the study, especially given the two durable confirmed partial responses, the emerging dose-response relationship, and the favorable safety and tolerability profile observed to date."

Dr. Cohen continued, "There is a high unmet medical need to address the adverse survival outcomes seen in patients with recurrent or metastatic EBV-positive NPC. Planning for success, we incorporated FDA’s Project Optimus initiative into the Phase 2 study design, which is intended to confirm the recommended Phase 2 dose of Nana-val that maximizes efficacy as well as safety and tolerability in patients with advanced EBV-positive solid tumors. Study sites are now open and enrolling the sixth dose cohort of the study, which is investigating the novel split daily dosing regimen at higher dose levels of Nana-val, and we are on track to expand into the Phase 2 portion of the study in 2024."

Key Data from the Oral ESMO (Free ESMO Whitepaper) Asia Congress Presentation
Interim data from the Phase 1b/2 study of Nana-val in patients with R/M EBV+ NPC revealed two ongoing confirmed partial responses (PRs) at higher dose levels plus new nonclinical data that support the evaluation of a novel split daily dosing (SDD) regimen.

Best antitumor responses to date have included two PRs (both ongoing for >10 months and >four months on study treatment) at the higher dose levels plus five stable diseases out of 17 patients treated to date.
Confirmed PR at the third dose level demonstrated >50% reduction in tumor size through 50 weeks and confirmed PR at the fifth dose level demonstrated ~30-40% reduction in tumor size through 14 weeks.
Increased antitumor activity observed in a preclinical murine EBV+ gastric cancer xenograft model supports investigation of Nana-val on an SDD schedule as a next step.
In comparison to once daily dosing, split dosing four hours apart each day increased the expression of EBV protein kinase, which translated into increased antitumor activity.
In comparison to intermittent (four days on/three days off) dosing, daily (seven days/week) dosing increased the exposure to Nana-val leading to a more sustained antitumor effect.
A copy of the ESMO (Free ESMO Whitepaper) Asia Congress presentation titled, "A Phase 1b/2 Study of Nanatinostat (Nstat) Plus Valganciclovir (VGCV) in EBV+ Solid Tumors and with Pembrolizumab (PEM) in Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC)," will be accessible on the Events and Webcasts page in the Investors section of Viracta’s website.

Investigative sites are now open for enrollment into the sixth dose cohort of the Phase 1b dose escalation portion of the study, which incorporates Nana-val’s novel SDD regimen. Once the Phase 2 dose (RP2D) is determined, the company plans to incorporate a dose-optimization cohort to confirm the RP2D based on safety and efficacy by randomizing up to 40 patients with R/M EBV+ NPC to receive either the RP2D or a dose level below the RP2D.

About the Phase 1b/2 Study of Nana-val in R/M EBV+ NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation part is designed to evaluate safety and to select the recommended Phase 2 dose (RP2D) of Nana-val in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC). Along with the U.S. Food and Drug Administration’s Project Optimus initiative at the start of Phase 2, up to 40 patients with R/M EBV+ NPC will be randomized to receive either the RP2D or a dose level below the RP2D in a dose-optimization cohort. Once the RP2D has been confirmed, up to 60 patients with R/M EBV+ NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to further evaluate antitumor activity, safety and tolerability, pharmacokinetics, and potential pharmacodynamic biomarkers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.