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Agenus Closes $200M Upfront BMS Collaboration and Announces FDA Acceptance of IND for Partnered Anti-TIGIT Bispecific Antibody, AGEN1777

On July 6, 2021 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents which includes checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported the closing of its global exclusive license with Bristol Myers Squibb for Agenus’ proprietary bispecific antibody program, AGEN1777, and the U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug (IND) application for this therapy (Press release, Agenus, JUL 6, 2021, View Source [SID1234584622]). AGEN1777 is an Fc-enhanced antibody in late preclinical development designed to target major inhibitory receptors expressed on T and NK cells to improve anti-tumor activity.

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"TIGIT is becoming an increasingly important immunotherapy target, and the Fc-enhanced and bispecific design of AGEN1777 could offer improved benefit, including the potential for both single-agent and combination activity," said Garo Armen, PhD, Chief Executive Officer of Agenus. "Together with our partner Bristol Myers Squibb, we look forward to advancing this agent into clinical studies with the goal of providing a meaningful new option for cancer patients."

Bristol Myers Squibb intends to advance the research and development of AGEN1777 in immuno-oncology for high priority tumor indications including non-small cell lung cancer.

Phase 1 dosing for AGEN1777 is expected to begin during the third quarter of 2021. This dose escalation study is designed to evaluate the safety, tolerability, and preliminary clinical activity of AGEN1777 as a single agent and in combination with a PD-1 inhibitor in patients with advanced solid tumors.

Under the terms of the agreement with Bristol Myers Squibb, Agenus receives a $200 million upfront payment in connection with the closing. The agreement also includes up to $1.36 billion in development, regulatory and commercial milestones in addition to tiered double-digit royalties on net product sales. Bristol Myers Squibb will become solely responsible for the development and any subsequent commercialization of AGEN1777 and its related products worldwide. Agenus will retain options to conduct clinical studies under the development plan, to conduct combination studies with certain other Agenus pipeline assets, and also, upon commercialization, to co-promote AGEN1777 in the US.

About AGEN1777
AGEN1777 is a potentially first-in-class bispecific anti-TIGIT antibody engineered with an enhanced Fc region for high binding affinity and improved T and NK cell activation.

Molecular Templates to Present at the Ladenburg Thalmann 2021 Healthcare Conference

On July 6, 2021 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates" or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer and other serious diseases, reported that it will provide a corporate update and participate in 1-on-1 investor meetings at the Ladenburg Thalmann 2021 Healthcare Conference, to take place July 13-14, 2021 (Press release, Molecular Templates, JUL 6, 2021, View Source [SID1234584621]).

Presentation details can be found below.

Date: Tuesday, July 13, 2021
Time: 4:00 PM ET
A live webcast of the presentation will be available in the "News and Events" section of the MTEM website at www.mtem.com. Additionally, a replay of the webcast will be available on MTEM’s website following the conference.

Arrowhead Announces Positive Interim Results from Phase 1b Study of ARO-HIF2 for Treatment of Clear Cell Renal Cell Carcinoma

On July 6, 2021 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported positive interim results from the first two cohorts of AROHIF21001, a Phase 1b dose-finding clinical study of ARO-HIF2, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC) (Press release, Arrowhead Pharmaceuticals, JUL 6, 2021, View Source [SID1234584620]). ARO-HIF2 is the first tumor-targeted investigational medicine to utilize Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform in a clinical trial. Arrowhead is currently enrolling the third planned patient cohort of AROHIF21001 and the company intends to present additional data at an appropriate medical congress.

James Hamilton, M.D., MBA, senior vice president of discovery and translational medicine at Arrowhead, said: "The AROHIF21001 Phase 1b study is designed to evaluate safety as well as preliminary pharmacodynamics and efficacy in an advanced ccRCC patient population. We believe that in the first two dose cohorts investigational ARO-HIF2 is showing clear signs of meaningful target engagement and some potentially early signs of efficacy in at least one patient. This is an encouraging start for the study. Specifically, in seventeen patients treated with investigational ARO-HIF2, nine had tumor biopsy material that could be evaluated. Seven of these nine tumor samples demonstrated reductions in HIF2α protein, as measured by immunohistochemistry H-score. The mean of these reductions was -48% with a range from -9% to -82%. In addition, one patient achieved a partial response with tumor shrinkage of approximately 65% and four additional patients in cohort 2 remain on study drug with stable disease. Tumors typically have a high level of heterogeneity and the patients in AROHIF21001 have advanced ccRCC and have failed multiple lines of treatment including checkpoint inhibitors and anti-VEGF regimens, so these early results in a heavily pre-treated population are encouraging for investigational ARO-HIF2 and our tumor-targeted platform broadly. ARO-HIF2 has been generally well-tolerated and we look forward to continued dose escalation."

Key Results from AROHIF21001

17 patients have been enrolled to receive intravenous injections of 225 mg weekly (cohort 1, n=7) or 525 mg weekly (cohort 2, n=10)
The study has progressed to a dose of 1050 mg weekly (cohort 3), which is currently enrolling patients
HIF2α protein H-score was assessed via immunohistochemistry
9 of 17 patients had tumor samples that could be evaluated
7 of 9 demonstrated reductions in HIF2α
Reductions ranged from -9% to -82% with a mean reduction of -48%
Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
In cohort 2, one subject had a partial response with approximately 65% tumor shrinkage and 5 had a best response of stable disease
4 subjects in cohort 2 remain on drug with stable disease with treatment durations between 12 and 24 weeks
To date, investigational ARO-HIF2 has been generally well tolerated at doses of up to 525 mg weekly
No cases of anemia related to drug have been reported
AROHIF21001 (NCT04169711) is a Phase 1b dose-finding clinical study in patients with advanced ccRCC to evaluate the safety of ARO-HIF2 and to determine the recommended Phase 2 dose. Secondary objectives include the assessment of pharmacokinetics and preliminary efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST). Exploratory objectives for AROHIF21001 are post-dose tumoral expression of HIF genes in response to treatment with ARO-HIF2, change in Karnofsky Performance Status (KPS), correlation of tumor response based on RECIST with tumor HIF2α gene expression and tumor integrin expression, correlation of integrin expression with changes in HIF gene expression, evaluation of serum biomarkers of ARO-HIF2 activity, correlation of RCC-related gene expression to ARO-HIF2 activity, and evaluation of plasma and urine metabolites.

MARKER THERAPEUTICS ANNOUNCES COMPLETION OF SAFETY LEAD-IN PORTION OF PHASE 2 STUDY IN POST-TRANSPLANT AML

On July 6, 2021 Marker Therapeutics, Inc. (Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported completion of the six-patient safety lead-in portion of the Company’s Phase 2 trial of MT-401, its lead MultiTAA-specific T cell product candidate, for the treatment of post-transplant acute myeloid leukemia (AML) (Press release, Marker Therapeutics, JUL 6, 2021, View Source [SID1234584619]).

"We are pleased with the results of the safety lead-in portion of the trial, in which all six patients met the safety endpoints following infusion of our MultiTAA-specific T cell therapy," said Mythili Koneru, M.D., Ph.D., Chief Medical Officer of Marker Therapeutics. "We are currently enrolling patients in the main portion of our first Company-sponsored trial and continue to activate clinical sites across the U.S. We are looking forward to further advancing MT-401 in this disease setting. Despite recent advances in how hematological malignancies are treated, patients remain in urgent need of new therapeutic options."

About Marker’s Phase 2 AML Post-Transplant Study

The multicenter Phase 2 AML study is evaluating the clinical efficacy of MT-401 in patients with AML following an allogeneic stem-cell transplant in both the adjuvant and active disease setting. In the adjuvant setting, approximately 120 patients will be randomized 1:1 to either MT-401 at 90 days post-transplant versus standard-of-care observation, while approximately 40 patients with active disease will receive MT-401 as part of the single-arm group.

The primary objectives of the trial are to evaluate relapse-free survival in the adjuvant group and determine the complete remission rate and duration of complete remission in active disease patients. Additional objectives include, for the adjuvant group, overall survival and graft-versus-host disease relapse-free survival while additional objectives for the active disease group include overall response rate, duration of response, progression-free survival and overall survival.

In April 2020, the FDA granted Orphan Drug designation to MT-401 for the treatment of patients with AML following allogeneic stem cell transplant.

Kura Oncology Announces Clinical Collaboration to Evaluate Tipifarnib in Combination with Alpelisib in Head and Neck Squamous Cell Carcinoma

On July 6, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported a clinical collaboration with Novartis to evaluate the combination of tipifarnib and alpelisib in patients with head and neck squamous cell carcinoma (HNSCC) whose tumors have HRAS overexpression or PIK3CA mutation and/or amplification. Tipifarnib is Kura’s farnesyl transferase inhibitor drug candidate currently in a registration-directed trial as a monotherapy in patients with HRAS mutant HNSCC. Novartis’ alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against the PI3Kα isoform.

"Our preclinical data suggest that HRAS and PI3Kα are co-dependent pathways involved in the development and maintenance of HNSCC in certain patient populations. Combining tipifarnib with alpelisib has the potential to provide a clinically meaningful increase in anti-tumor activity compared to when inhibiting either pathway alone," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "We believe this clinical collaboration will enable us to potentially expand the use of tipifarnib to a significantly higher percentage of patients with advanced HNSCC. We look forward to initiating the combination trial in the second half of 2021."

The Phase 1/2 KURRENT trial is a biomarker-defined cohort study designed to evaluate the safety, determine the recommended combination dosing and assess early anti-tumor activity of tipifarnib and alpelisib for the treatment of HNSCC patients whose tumors are dependent on HRAS and/or PI3Kα pathways, which is approximately 50% of HSNCC patients, according to The Cancer Genome Atlas (TCGA).

Under the collaboration, Kura maintains global development and commercial rights to tipifarnib.

About HNSCC

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, accounting for more than 500,000 new cases each year. Despite advances in immunotherapy, the prognosis for advanced HNSCC patients remains poor, with an estimated median overall survival of 13-15 months in patients when stratified by PD-L1 expression. Although the anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, was approved more than a decade ago, development of biomarker-directed therapies in HNSCC has been stymied by the limited number of druggable targets in the genomic landscape and the challenge of managing drug refractory recurrent/metastatic HNSCC.

About Tipifarnib

Tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase, which has been granted Breakthrough Therapy and Fast Track Designations by the FDA for the treatment of patients with HRAS mutant HNSCC. In addition to HNSCC, tipifarnib has demonstrated encouraging clinical activity in multiple additional genetically defined tumor types. Kura has received multiple issued patents for tipifarnib, providing patent exclusivity in the U.S. and foreign countries.