On July 6, 2021 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported the publication of pre-clinical research relating to its second-generation immuno-oncology LBP MRx1299 improving the activity of CAR-T (Press release, 4d Pharma, JUL 6, 2021, View Source [SID1234584624]).

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The research, conducted in collaboration with the Philipps-University Marburg, Germany, and Universitätsklinikum Würzburg, Germany, and published in Nature Communications, demonstrates the ability of the bacterium Megasphaera massiliensis or its short chain fatty acid (SCFA) metabolite pentanoate to enhance the anti-tumor activity of cytotoxic T lymphocytes (CTL) and CAR-T therapies in animal models of cancer, resulting in better tumor clearance.

4D pharma identified M. massiliensis MRx1299 using its MicroRx platform and previously showed MRx1299 to have specific histone deacetylase (HDAC) inhibitory activity and be a rare prolific producer of pentanoate. This led to discussions with the lab of Dr. Alexander Visekruna, corresponding author on the recent publication, due to their work investigating the effects of SCFAs on immune cell subsets.

"Our existing clinical oncology programs, such as the study of MRx0518 and Keytruda in refractory patients, have shown the important role our live biotherapeutics have to play in the fight against cancer in combination with immunotherapies. Using the MicroRx platform we have now shown we have the potential to improve the efficacies of cell therapies such as CAR-T," commented Dr. Imke Mulder, Research Director, 4D pharma. "This demonstrates not only the importance of Live Biotherapeutics as a new modality poised to revolutionize the treatment of a wide range of cancers, but also the power of our MicroRx platform to continue making significant discoveries and advances in this field."

"Collectively, these results suggest that low-abundant commensal bacterial species such as M. massiliensis and their selective metabolites such as pentanoate, rather than broadly distributed and abundant commensals, may be used as specific microbial biotherapeutics to enhance anti-tumor immunity and increase the efficacy of CAR-T therapy for treating tumors," commented Dr Alexander Visekruna of the Institute for Medical Microbiology and Hospital Hygiene at Philipps-University Marburg. "Combined therapies including immune checkpoint inhibitors or CAR-T and simultaneous provision of low-abundant bacteria synthesizing specific metabolites as an adjunctive agent may be therapeutically useful."

Luu et al., Nature Communications, ‘Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer’ View Source

On July 6, 2021 MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA therapeutics, reported that Eli Lilly and Company has entered into a definitive agreement under which it will make a direct equity investment in MiNA (Press release, MiNA Therapeutics, JUL 6, 2021, View Source [SID1234584623]).

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The equity investment of approximately $15m follows the recent agreement between the two companies to develop novel drug candidates using MiNA’s proprietary small activating RNA (saRNA) technology platform, announced on 11 May 2021.

Proceeds from the equity investment will be used to advance and expand MiNA’s internal pipeline of saRNA therapeutics, which is initially focused on immuno-oncology and genetic diseases.

Robert Habib, CEO of MiNA Therapeutics, commented:
"We welcome Lilly as an important shareholder in MiNA. This investment from Lilly, together with our recently announced multi-target research collaboration, represents an important endorsement of our saRNA platform."

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.

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]).

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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.

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.

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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.